Gastroesophageal Disease and Environmental Exposure: A Systematic Review

Gastroesophageal Disease and Environmental Exposure: A Systematic Review | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Gastroesophageal Disease and Environmental Exposure: A Systematic Review Daniel Hyun Kim, Sanjiti Podury, Aida Fallah Zadeh, Sophia Kwon, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4650430/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 02 Jul, 2025 Read the published version in Scientific Reports → Version 1 posted 12 You are reading this latest preprint version Abstract Environmental exposure-associated disease is an active area of study, especially in the context of increasing global air pollution and use of inhalants. Our group is dedicated to the study of exposure-related inflammation and downstream health effects. While many studies have focused on the impact of inhalants on respiratory sequelae, there is growing evidence of the involvement of other systems including autoimmune, endocrine, and gastrointestinal. This systematic review aims to provide a recent update that will underscore the associations between inhalation exposures and upper gastrointestinal disease in the contexts of our evolving environmental exposures. Keywords focused on inhalational exposures and gastrointestinal disease. Primary search identified n = 764 studies, of which n = 64 met eligibility criteria. In particular, there was support for existing evidence that PM increases the risk of upper gastrointestinal diseases. Smoking was also confirmed to be major risk factor. Interestingly, studies in this review have also identified waterpipe use as a significant risk factor for gastroesophageal reflux and gastric cancer. Our systematic review identified inhalational exposures as risk factors for aerodigestive disease, further supporting the association between environmental exposure and digestive disease. However, due to limitations on our review’s scope, further studies must be done to better understand this interaction. Systematic Review Environmental Exposure Smoking Particulate Matter Aerodigestive Disease Figures Figure 1 Figure 2 INTRODUCTION Exposome-associated morbidity and mortality is a global health concern. Environmental exposures that individuals encounter over their lifetimes include air pollution, water pollution, diet, and radiation. The exposome’s rate, volume, and variety have been linked to heterogenous negative health effects, but mechanisms remain elusive in many disease states. Studying the exposome provides valuable insights into the interplay between environmental factors and human health. 1 Of the various environmental exposures, inhalational exposure has been of great interest, especially in the context of rising levels of global air pollution due to global warming, wildfires, wars, and population growth. Studies investigating the link between environmental exposures and disease have the potential to impact millions globally. Air pollution is associated with 7-million premature deaths annually, and levels have steadily risen over the past few decades. 2–3 Over half of the world’s population are exposed to levels of air pollution that are substantially above the WHO Air Quality Guidelines. 4 There are a greater proportion of non-communicable disease attributable to environmental exposure in developing countries that utilize industrial production factories, primary contributors to emissions. 5 Particulate matter (PM) exposure, in particular, is a global cause of significant aerodigestive morbidity and mortality. 6–46 The destruction of the World Trade Center (WTC) on September 11, 2001 (9/11) led to intense PM exposure of first responders and inhabitants of New York City (NYC). 15–46 WTC-PM exposure is associated with obstructive airways disease (OAD). PM was also found to have associations with gastroesophageal diseases, such as gastroesophageal reflux disease (GERD) and Barrett’s Esophagus (BE). 47–49 Approximately 44% of WTC rescue/recovery workers had developed GERD symptoms by 2005. 50 In contrast, GERD has a prevalence of 20% in the US. 51–53 There is also evidence of comorbid GERD and OAD, as WTC-exposed firefighters with OAD had 3-fold higher risk of developing GERD. 49,54 GERD is the most prevalent gastrointestinal disorder affecting at least 20% of the US population, and leading to substantial morbidity. 55 Globally, GERD prevalence is 10–25%. 55,56 Aerodigestive complications also include BE, and malignancy such as esophageal adenocarcinoma (EAC). 15,57,58 Aerodigestive disease can also induce or worsen respiratory disease such as airway hyperreactivity (AHR). This may be explained by the clearing mechanism of the respiratory system and its close proximity to the digestive system at the pharynx. However, this is an area of active investigation. 59 Prior systematic reviews on the topic have only focused on single inhalational exposures and/or single diseases/outcomes. 60–65 Our systematic review focuses on the exposome in a more holistic manner in order to assess its effects on the scope of gastroesophageal diseases on a greater scale. We investigated the associations between exposure (particulate matter, smoking, waterpipe smoking) with diseases of the upper gastrointestinal tract (GERD, Barrett’s and malignancy). METHODS Review Strategy. Our systematic review adhered to the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines. 66,67 Our Population, Exposure, Outcome (PEO) question was to investigate among adult populations (P) , whether there is an association between inhalational exposure (e.g., air pollution, cigarette/tobacco smoke, marijuana smoke, vape/e-cigarette aerosols) (E) and esophageal or gastric disorders/disease (O) . PubMed searches were conducted on May 1, 2024 as per the protocol of our systematic review registered on PROSPERO on April 29, 2024 and can be accessed at Prospero ID 536834. The following MeSH Terms were searched for using the MeSH Database: ("Particulate Matter"[Mesh]) OR ("Vaping"[Mesh]) OR ("Smoking"[Mesh]) OR ("Smoking Devices"[Mesh]) OR ("Tobacco Use"[Mesh]) OR ("Tobacco Use Cessation Devices"[Mesh]) OR ("Electronic Nicotine Delivery Systems"[Mesh]) OR ("E-Cigarette Vapor"[Mesh]) OR ("Inhalant Abuse"[Mesh]) OR ("Marijuana Smoking"[Mesh]) OR ("Marijuana Use"[Mesh]) OR ("Marijuana Abuse"[Mesh]) OR ("Cannabis"[Mesh]) OR ("Cannabinoids"[Mesh]) [AND] (“Stomach Diseases”[Mesh]) OR (“Esophageal Diseases”[Mesh]) The complete listing of associated terms that were searched for with each of the above Mesh terms, can be found at MeSH Database. For example, when searching for “stomach diseases” under its associated Mesh term, we were able to search for Reflux, Gastritis, Peptic Ulcer, Stomach Neoplasms, Zollinger-Ellison syndrome, etc. Reference-list screening was also used. For this review, we have defined environmental exposure to include PM 2.5 , PM 10 , tobacco/cigarette smoke, vape/e-cigarette aerosols, and marijuana/cannabinoid inhalation. We have defined esophageal and gastric disease to include the following: gastroesophageal reflux disease (GERD), Barrett’s Esophagus (BE), peptic ulcer disease (PUD), esophagitis, gastritis, esophageal cancer, and stomach cancer. Study Criteria. Studies were included if they (1) discussed the environmental/occupational exposure to inhalants, specifically, PM 2.5 , PM 10 , tobacco/cigarette smoke, marijuana smoke, and/or vape/e-cigarette vapor, (2) evaluated effects of exposures on esophageal or gastric diseases, (3) performed on adult human subjects, (4) were written in English, and (5) were published within the last 10 years. Studies were excluded if they (1) were not original research, (2) consisted of translational research, (3) were case reports or series, or (4) were conducted on a pediatric population. Data Extraction. Articles were reviewed and data regarding study design, patient characteristics, sample size, and tool used were extracted. Results from database searches were filtered for full-text articles, human subjects, English language, and publication date and imported into Endnote X9. Original research papers were reviewed for (title, abstract, and full text) to ascertain eligibility. We examined references cited in the relevant articles. All results were screened by DHK and SP and further independently evaluated by AN. Disagreements were resolved by consensus. Risk of Bias Assessment. Systematic review inherent bias (selection, detection, performance, and reporting) was addressed through study design/search algorithm. Selection bias was addressed by having pre-determined inclusion, exclusion criteria and distinct definitions. Detection and performance bias were addressed by having at least two rounds of screening individually performed by DHK and SP. Reporting bias was minimized by using PubMed search filters for peer-reviewed published articles of human subjects written in English and removing duplicates. The Newcastle-Ottawa Scale (NOS), a domain-based approach was used to assess the degree of bias. 68 Scales adapted for case-control and cross-sectional studies were used. Total scores obtained by the scale were converted to AHRQ standards or as done in previous studies to reflect the quality of each paper: “good” (green), “fair” or “satisfactory” (yellow), and “poor” or “unsatisfactory” (red). 69 Ethics Approval. This study does not require ethical approval as it involves a review of publicly available research and utilized anonymized original data. Table 1 Study Characteristics Study Country Exposure/ Design Study Size/ Time Period Outcome of Interest Relevant Findings 1 Almadi, 2014 70 Saudi Arabia Smoking Cohort Study 4 shopping centers, Riyadh / N = 1,265 Dec. 2012-Jan. 2013 GERD • Higher prevalence of GERD in smokers (51.63% vs. 44.41%), but not significant (p = 0.09) • No significant association between GERD and smoking (OR: 1.34; 95% CI: 0.95–1.87) 2 Baroudi, 2014 71 Tunisia Smoking Case-Control Study Salah Azaiez Insititue of Oncology N = 348 2009–2010 GCa • Smoking more than 10 cigarettes a day is significantly associated with an increased risk in gastric cancer (OR: 3.66; 95% CI: 1.82–7.78). 3 Begovic, 2015 72 North Macedonia Smoking Cohort Study 2 University Clinics / N = 67 2014 PUD • Smoking is an important risk factor and more than half of ulcer patients were smokers (65.75%). • Percent difference in relation to those who are non-smokers is statistically significant (p = 0.0000). 4 Chuang, 2019 73 Taiwan Smoking Cross-Sectional Study 4 hospitals in SW Taiwan / N = 8,135 Apr. 2008-Dec. 2013 E / BE / ECa / PUD / GCa • Current tobacco use was a significant risk factor for RE (aOR: 1.26; 95% CI: 1.09–1.46), BE (aOR: 1.47; 95% CI: 1.08-2.00) and PUD (1.79; 95% CI: 1.52–2.10), but nonsignificant for ESCC (aOR: 1.40; 95% CI: 0.57–3.43) and GC (aOR: 1.24; 95% CI: 0.53–2.91). • Higher cumulative amounts of tobacco use were at higher risk for PUD (aOR: 1.92; 95% CI: 1.60–2.31) 5 Crews, 2016 74 US Smoking Cohort Study Olmsted County, MN N = 205 Apr. 2011-Oct. 2013 E / BE • In a univariate analysis, ever tobacco use was not a significant risk factor for EE/BE (OR: 0.9; 95% CI: 0.5–1.9) 6 Dore, 2016 75 Italy Smoking Cohort Study Sassari, Sardinia / N = 5156 Jan. 2002-Dec. 2013 BE / GERD • Adjusted ORs of BE and GERD for current smokers were 0.447 (95% CI; 0.199–1.002) and 1.392 (95% CI: 1.085–1.787), respectively. 7 Etemadi, 2017 76 Iran Smoking / Waterpipe Smoking Cohort Study Valashahr, Fars / N = 9264 2012–2017 GERD • Strongest associations of waterpipe smoking were with ‘severe and frequent reflux’ (OR: 1.30; 95% CI: 1.08–1.56) • Former use had a stronger association with ‘severe reflux’ and (OR: 1.29; 95% CI: 1.06–1.56) and current use with ‘frequent reflux’ (OR: 1.18; 95% CI: 1.03–1.36). • Current cigarette use was a significant risk factor for “any reflux” among men (OR: 1.20; 95% CI: 1.02–1.40) • Increases in reflux prevalence associated with waterpipe use duration and intensity. 8 Filiberti, 2015 77 Italy Smoking Case-Control Study 12 endoscopic units N = 1420 Mar. 2009-Oct. 2012 E / BE • Associations shown between smoking and BE that was independent of intensity, age at initiation, GERD and dependent of duration and years since cessation • Among current smokers who smoke > 18 cigarettes/day, ORs for RE and BE were 1.31 (95% CI: 0.80–2.17) and 1.86 (95% CI: 0.98–3.16), respectively. • Risk of BE significantly increased for those who had smoked for > 32 years (OR: 2.44; 95% CI; 1.33–4.45) and those whom < 9 years have passed since quitting (OR: 2.11; 95% CI: 1.19–3.72) 9 Ghoshal, 2017 78 India Smoking Cross-Sectional Study Uttar Pradesh, Jaunpur District / N = 2876 GERD • On univariate analysis, tobacco smoking (105 [35.2%] vs. 672 [27.1%]) was associated with GERD. • On multivariate analysis, tobacco smoking (OR: 1.36; 95% CI: 0.99–1.88) was associated with GERD 10 Jayalekshmi, 2015 79 India Smoking Cohort Study Karunagappally Cohort, Kerala / N = 65553 men 1990–2009 GCa • Bidi smoking was significantly associated with GCa risk (RR: 1.6; 95% CI: 1.0-2.5; P = 0.042), but cigarette smoking was not (RR: 0.8; 95% CI: 0.5–1.2) • Bidi smoking increased risk of GCa among never cigarette smokers (RR: 2.2, 95% CI: 1.3-4.0) • GCa risk increased with the number of bidis smoked daily (P = 0.012) and with duration of bidi smoking (P = 0.036) 11 Jayalekshmi, 2021 80 India Smoking Cohort Study Karunagappally Cohort, Kerala / N = 65528 men Jan. 1990-Dec. 2013 ECa • RRs for current bidi and cigarette smokers were 1.4 (95% CI: 0.98–2.12) and 1.3 (95% CI: 0.9–1.8), respectively. • Higher risks for ESCC observed for current bidi smokers (RR: 2.2; 95% CI: 1.3–3.8) and cigarette smokers (RR: 1.6; 95% CI: 1.0-2.5) 12 Kayamba, 2015 81 Zambia Smoking Case-Control Study University Teaching Hospital, Lusaka / N = 100 Oct. 2013-May 2014 ECa (ESCC) • Ever smokers showed greater risk of developing ESCC (OR: 8.0; 95% CI: 2.8–22.7) • Much greater proportion of cases than controls (38% vs 0%) were current smokers (p < 0.000) 13 Kim, Chang, 2019 82 South Korea Smoking Cohort Study Kangbuk Samsung Hospital, Seoul / N = 199235 Jan. 2011-Dec. 2017 GCa (IM) • For current smokers, the multivariable-adjusted HR for men and women were 1.51 (95% CI: 1.41–1.61) and 0.94 (0.73–1.22), respectively. 14 Kim, Jang, 2018 83 South Korea Smoking Cohort Study N = 2368 Mar. 2013-Dec. 2015 GERD • Former smokers showed a significantly greater risk of GERD (OR: 1.93; 95% CI: 1.12–3.35). • Current smokers showed a non-significantly greater risk of GERD (OR: 2.31; 95% CI: 0.94–5.66). 15 Kim, Jung, 2019 84 South Korea Smoking Cross-Sectional Study Ewha Womans University Mokdong Hospital / N = 10158 Jan. 2015-Dec. 2016 E / GERD • Among men, smokers yielded ORs for RE and GERD of 1.67 (95% CI: 1.30–2.16) and 1.48 (95% CI: 0.85–2.57), respectively. • Among women, smokers yielded ORs for RE and GERD of 3.47 (95% CI: 1.61–7.48) and 1.35 (95% CI: 0.68–2.67), respectively. 16 Koca, 2015 85 Turkey Smoking Case-Control Study Erzurum Regional Training and Research Hospital, Anatolia / N = 408 Jan. 2008-Mar. 2014 ECa • Smoking (X 2 = 7.629; p = 0.022) was significantly higher in the patient group than the control group. 17 Koutlas, 2018 86 US Smoking Case-Control Study University of North Carolina / N = 340 2011–2015 E • EE cases were less likely to have ever smoked cigarettes compared to endoscopy-based non-EE controls (23% vs. 47%, P < 0.001). • aOR for ever-smoking was 0.47 (95% CI: 0.17–0.76). 18 Lai, 2016 87 Vietnam Smoking / Waterpipe Smoking Case-Control Study 3 major hospitals, Hanoi / N = 1082 Feb. 2003-Apr. 2011 GCa • WPT smoking was positively associated with GCa risk. Significantly high GCa risk in current WPT smokers (OR: 1.8; 95% CI: 1.3–2.4) • Current cigarette smoking was not a significant risk factor for GCa (OR: 1.1; 95% CI: 0.8–1.4) • No significant interaction between effects of WPT and cigarette smoking on GCa risk. 19 Le, 2022 88 Vietnam Smoking / Waterpipe Smoking Cohort Study 3 Northern Vietnam Provinces / N = 25619 2008–2019 GCa • Significantly higher GCa mortality among ever-smokers than never-smokers (aHR: 2.43; 95% CI: 1.35–4.36) • Exclusive WPT smokers showed the highest risk (HR: 3.22; 95% CI: 1.67–6.21), followed by smokers of both WPT and cigarette (HR: 1.99; 95% CI: 0.89–4.63), then exclusive cigarette smokers (HR: 1.90; 95% CI: 0.88–4.07). 20 Lee, 2016 89 South Korea Smoking Case-Control Study Konkuk University Medical Center / N = 2961 Jan. 2010-Jun. 2014 E (Asymptomatic) • Current smoking was an independent predisposing factor for AEE (OR 1.366; 95% CI: 1.068–1.748) 21 Levenstein, 2017 90 Denmark Smoking Cohort Study Copenhagen County / N = 3365 1982 PUD • Age-, gender-, and socioeconomic status-adjusted associations were significant for smoking (HR: 1.8; 95% CI: 1.1–2.8). 22 Li, Guo, 2022 91 China PM 2.5 Cross-Sectional Population Study 388 cancer registry institutes, Mainland China 2007–2015 ECa • Significantly positive association between PM 2.5 and EC incidence. • Lag effect of 4 years showed the greatest risk for males and females at 1.32% (95% CI: 1.20–1.45%) and 2.70% (95% CI: 2.49–2.92%), respectively. 23 Li, Jing , 2021 92 China PM 2.5 Cross-Sectional Population Study 213 Prefectural Level Cities, Mainland China 2000–2015 ECa • Stronger association between PM 2.5 and incidence observed in low urbanization groups, and association was stronger for females than males. 24 Li, He, 2024 93 China PM 2.5 Cross-Sectional Study Jiangsu Province / N = 524019 2015–2020 ECa/GCa • Long-term exposure to black carbon, organic carbon, nitrate, and ammonium was significantly associated with esophageal and stomach cancer. • Sulfate exposure was significantly associated with stomach cancer. 25 Lin, Wu, 2020 94 China Smoking Case-Control Study Xianyou County, Fujian Province / N = 1244 Mar. 2013-Jan. 2017 GCa • Current cigarette smoking status was attributed to 83% increased risk of GCa (OR: 1.83, 95% CI: 1.19–2.80) • Smokers with longer duration of smoking (≥ 20 years) or started at later age (≥ 20 years) had nearly twofold increased risk of GCa vs. nonsmoker (OR: 1.97; 95% CI: 1.28–3.04, OR: 2.02; 95% CI: 1.30–3.14, respectively). 26 Lin, Shih, 2022* 95 Taiwan PM 2.5 Cross-Sectional Population Study Entire Population of Taiwan / N = 23.57 million 2010–2017 ECa • Average number of deaths from esophagus cancer decreases 0.17 (95% CI: -0.22, -0.12) per 100,000 people with increasing average PM 2.5 concentration. 27 Martinucci, 2018 96 Italy Smoking Cross-Sectional Study University of Pisa / N = 3012 Oct. 2016-May 2017 GERD • In the set of students with GERD, percentage of smokers was higher. • In a multivariate analysis, smoking status showed an increased risk of GERD (OR: 1.6; 95% CI: 1.25–2.05) 28 Matsuzaki, 2015 97 Japan Smoking Case-Control Study Keio University Hospital / N = 2608 Oct. 2012-Nov. 2013 E / BE • Current smoking showed risks for RE and BE of OR: 1.79 (95% CI: 1.23–2.60) and OR:1.37 (0.83–2.26), respectively. 29 Miftahussurur, 2018 98 Indonesia Smoking Case-Control Study Surabaya / N = 104 Oct. 2014-Nov. 2015 GERD • Smokers had a significantly higher risk of GERD compared to non-smokers (OR: 3.60; 95% CI: 1.298–9.955) 30 Minami, 2018 99 Japan Smoking Cohort Study Miyagi Cancer Center Hospital / N = 1576 Jan. 1997-Dec. 2010 GCa • Current smokers had increased risk of stomach cancer death in a multivariate adjusted model (HR: 1.25; 95% CI: 0.92–1.69). 31 Mlombe, 2015 100 Malawi Smoking Case-Control Study 2 tertiary teaching hospitals / N = 276 Jan. 2011-Feb. 2013 ECa • In unadjusted analysis, odds of developing ESCC was 11.2 times higher among smokers than non-smokers, and in adjusted analysis it was 5.4 times higher. • OR: 11.2 (95% CI: 5.2–24.0) and aOR: 5.4 (2.0-15.2) 32 Moses, 2017 101 Malawi Smoking Cohort Study Kamuzu Central Hospital, Lilongwe / N = 172 Jun. 2009-Sept. 2012 ECa • Esophageal cancer was among the commonest cancers in the cohort (n = 172; 34.5%). • Patients with esophageal cancer were more likely to be smokers (OR: 2.02). 33 Navab, 2015 102 US Smoking Cross-Sectional Study Tertiary care center, PA N = 158 1999–2008 BE • Correlation coefficients for current and prior tobacco use were 0.73 (95% CI: 0.50–1.06) and 0.92 (0.64–1.31), respectively. 34 Nguyen, 2022 103 Vietnam Smoking / Waterpipe Smoking Case-Control Study Bach Mai Hospital / N = 226 Jan. 2018-Dec. 2018 GCa • Compared to never tobacco smokers, risk of GCa significantly increased among tobacco smokers (OR: 2.95; 95% CI: 1.26–6.90, p = 0.013) • For types of tobacco, increased risk was observed in exclusively cigarette smokers (OR: 3.26; 95% CI: 1.24–8.55, p = 0.017) and WPT smokers (OR: 2.90; 95% CI: 1.05–7.97, p = 0.039). 35 Okamoto, 2023 104 Japan Smoking Cross-Sectional Study Ebina Medical Center, Ebina / N = 965 Jan. 2015-Jun. 2015 RE • Compared to never smokers, former and current smokers showed increased risk of RE (OR: 1.5; 95% CI: 0.9–2.4, p = 0.08) and (OR: 2.4; 95% CI: 1.5–3.9, p = 0.01), respectively. 36 Okello, 2016 105 Uganda Smoking Case-Control Study Mbarara Regional Referral Hospital / N = 209 Jan. 2003-Dec. 2014 ECa • In multivariate analysis, smoking was not statistically associated with ESCC. • According to univariate analysis, smoking was significantly associated with ESCC (OR: 2.93; 95% CI: 1.43–5.71, p = 0.003). On multivariate analysis OR was 1.38 (95% CI: 0.41–4.67, p = 0.600). 37 Pan, 2019 106 China Smoking Cross-Sectional Study Huai’an, Jiangsu Province / N = 11518 Jan. 2011-Dec. 2017 ECa • Excessive smoking was associated with an increased risk of esophageal precancerous lesions (EPL) • Consuming > 30 cigarettes/day was significantly associated with EPL (OR: 1.75; 95% CI: 1.09–2.80). • Having 40 or more pack-years of cumulative amount of smoking was also significantly associated with EPL (OR: 1.40; 95% CI; 1.03–1.89). 38 Park, Kim, Jung, 2022 107 South Korea Smoking Cohort Study Korea National Health Insurance Database / N = 43380 2002–2013 PUD • Compared to the never-never group, all other groups had significantly adjusted HRs for gastroduodenal ulcer. • HR for current-current smokers was 1.379 (95% CI: 1.256–1.513). • Heavy smokers had the highest risk, followed by moderate and light smokers. 39 Park, Kim, Oh, 2022 108 South Korea Smoking Cohort Study Korea National Health Insurance Database / N = 97700 2003–2014 GCa • Compared to the never-never group, current smokers had higher HRs for gastric Ca. • HR for current-current smokers was 1.589 (95% CI: 1.355–1.864). • Risk for gastric cancer was highest in heavy smokers, followed by moderate smokers. 40 Quan, 2015 109 Canada PM 2.5 , PM 10 Case-Crossover Study Calgary (Discovery) and Edmonton (Replication) / N = 1374 and 1159 2004–2010 PUD • When air pollution exposures were assessed as 3-, 5-, and 7- day averages, pollutants were inversely associated with UGIB in the discovery cohort. • 5-day averages of PM 2.5 and PM 10 had ORs of 0.75 (95% CI: 0.61–0.90) and 0.87 (95% CI: 0.75-1.00), respectively. 41 Rafiq, 2020 110 India Smoking / Second-Hand Smoking Case-Control Study Kashmir / N = 2367 Sept. 2008-Jan. 2012 ECa • Among never-tobacco users, the association between ever exposure to SHS and ECa risk were (OR: 1.32; 95% CI: 0.43–4.02) • Non-smokers exposed to SHS had OR of 1.25 (95% CI: 0.66–2.38), whereas active smokers not exposed to SHS had OR of 1.49 (95% CI: 1.08–2.04). 42 Ramos, 2018 111 Brazil Smoking Case-Control Study Sao Paolo / N = 739 2001–2007 GCa • Former and current smokers had ORs of 2.25 (95% CI: 1.53–3.31) and 2.67 (95% CI: 1.72–4.13), respectively. • Smoking habit was associated with increased risk in all quartiles of consumption analyzed. 43 Rao, 2022 112 China PM 2.5 Cross-Sectional Study Fujian Province / N = 5479 Jan. 2016-Dec. 2016 ECa • Spatial distribution of hospitalization rate of ECa in 2016 was not consistent with that of concentration of PM 2.5 in same year. • Concentration of PM 2.5 in 2003 and 2004 had strongest correlation with hospitalization rate of ECa in 2016, with Pearson correlation coefficient r value of -0.365. 44 Sadafi, 2024 113 Iran Smoking Cross-Sectional Study Ravansar / N = 9631 2014–2023 GERD • The odds of GERD among current smokers was 23% higher than non-smokers (OR: 1.23; 95% CI: 1.02–1.55) 45 Schmidt, 2020 114 Germany Smoking Case-Control Study Southern Germany and Augsburg / N = 587 and 1976 2013–2017 BE • BE cases were statistically significantly more likely to smoke (32.3% vs 46.1% nonsmokers). • Male patients with BE were significantly more likely to smoke (28.2% vs 38.3% non-smokers) • 67.7% of BE cases were ever-smokers. 46 Seo, 2020 115 South Korea PM 2.5 , PM 10 Cross-Sectional Study Korea National Health Insurance Database / N = 200000 2002–2017 GERD • The final model of the study significantly predicted GERD-related medical utilization. • In particular, PM 2.5 and CO were identified as risk factors for GERD. 47 Sewram, 2016 116 South Africa Smoking Case-Control Study 3 major public referral hospitals, East Cape Province / N = 1858 Nov. 2001-Feb. 2003 ECa • For males, ever smokers had 4-fold increased odds compared to never smokers (OR: 4.11; 95% CI: 2.55–6.65) • For females, ever smokers had 3.5-fold increase odd compared to non-smokers (OR: 3.45; 95% CI: 2.47–4.82). 48 Simba, 2023 117 Kenya, Tanzania, Malawi Smoking Case-Control Study Eldoret, Kenya; Moshi, Tanzania; Blantyre, Malawi / N = 623, 1131, 870 Aug. 2013-May 2020 ECa • Ever-tobacco use was associated with increased ESCC risk in all countries: Tanzania (OR: 3.09; 95% CI: 1.83–5.23), Malawi (OR: 2.45; 95% CI: 1.80–3.33), and lesser in Kenya (OR: 1.37; 95% CI: 0.94-2.00). Combined OR: 2.15 (95% CI: 1.72–2.68) • ESCC risk increased in with tobacco intensity and smoking duration. • In all three countries, smoking tobacco showed increased risk of ESCC (OR: 2.28; 95% CI: 1.80–2.89). 49 Song, 2024 118 South Korea Smoking Cross-Sectional Study Seoul National University Bundang Hospital / N = 14598 May 2003-Feb. 2020 GCa • In the univariate analysis smoking was significantly associated with single GCa and SGMC in all patients (OR: 0.971; 95% CI: 0.694–1.359) and in EGCa and AGCa patients (OR: 1.200; 95% CI: 0.899–1.602 and OR: 0.468; 95% CI: 0.231–0.949, respectively) • Multivariate analysis, smoking was significantly associated with single GCa and SGMC in AGCa patients. 50 Spreafico, 2017 119 US / Canada Smoking Cohort Study Boston, MA and Toronto, Ontario / N = 564 (235; 329) 1999–2004 & 2006–2011 ECa • Smoking conferred worse overall survival in the combined Boston-Toronto Cohort with aHR of 1.22 (95% CI: 1.15–1.43) for each 20 pack-year increase. 51 Sun, 2023 120 China Smoking / PM 2.5 Cohort Study China Kadoorie Biobank / N = 510125 2005–2017 ECa • A linear concentration-response relationship between long-term PM 2.5 exposure and ECa. • Each 10-µg/m 3 increase in PM 2.5 , the HR for ECa was 1.16 (95% CI:1.04–1.30) • Using lowest group of PM 2.5 exposure as reference, HRs for other quartile groups, from low to high, were 1.09 (95% CI: 0.86–1.37), 1.28 (95% CI: 0.98–1.66), and 1.32 (95% CI: 1.01–1.72). • Subgroup analyses showed ever smoking had an HR of 1.18 (95% CI: 1.04–1.35). 52 Thrift, 2022 121 US Smoking Case-Control Study Houston, TX / N = 1962 GCa (IM) • Compared to never smokers, current smokers had 2-fold increased risk for gastric intestinal metaplasia (OR: 2.05; 95% CI: 1.47–2.85). • Among ever smokers, increasing duration and total dose were significantly associated with increased risk (p = 0.004 and 0.01, respectively). 53 Tsai, 2019 122 Taiwan PM 2.5 , PM 10 Case-Crossover Study Taipei / N = 23205 2009–2013 PUD • Increases in both PM 2.5 (OR: 1.14; 95% CI: 1.09–1.18) and PM 10 (OR: 1.05; 95% CI: 1.01–1.08) were significantly associated with increased risk of hospital admissions on warm days. • On cool days, only increases in PM 10 were found to be significantly associated with increased risk of hospital admission (OR: 1.04; 95% CI: 1.02–1.07). 54 Wang, Leena, 2016 123 India Smoking Cross-Sectional Study Trivandrum District / N = 1072 2010–2011 GERD • No association between cigarette smoking and risk of GERD. • For the association of ever-smokers and risk of GERD, a mutually-adjusted analysis yielded OR of 0.7 (95% CI: 0.4–1.2). 55 Wang, Katki, 2021 124 US Smoking Cohort Study NIH-AARP Cohort / N = 490605 1995–2011 ECa/GCa • For esophageal cancers, current smoking yielded HRs of 5.75 (95% CI: 3.90–8.49) for ESCC and 3.16 (95% CI: 2.54–3.92) for EADC. • For gastric cancers, current smoking yielded HRs of 3.16 (95% CI: 2.42–4.13) for GADC and 1.61 (95% CI: 1.27–2.05) for GNCA. 56 Wei, 2021 125 China Smoking Case-Control Study Feicheng, Shandong / N = 464 Jul. 2013-Apr. 2014 ECa • Ever smoking was associated with 3.11-fold increase in ESCC risk (OR: 3.11; 95% CI: 1.63–6.05) • For each cigarette-years increase in smoking index, ESCC risk increased by 56% (OR: 1.56; 95% CI: 1.18–2.13). 57 Wong, 2016 126 China Smoking / PM 2.5 Cross-Sectional Study Hong Kong / N = 66820 Jul. 1998-Dec. 2001 PUD • Adjusted HR for PUD hospitalization per 10 µg/m 3 of PM 2.5 was 1.18 (95% CI: 1.02–1.36). • Associations with PM 2.5 were significant for gastric ulcers (HR: 1.29; 95% CI: 1.09–1.53) but not for duodenal ulcers (HR: 0.98; 95% CI: 0.78–1.22) • For other variables, current smokers were to have significantly increased risk for hospitalization of PUD (HR: 1.59; 95% CI: 1.37–1.84). 58 Wu, 2021 127 China PM 2.5 / PM 10 Ecological Study Yinzhou District, Ningbo City, Zhejiang Province / N = 204257 Jan. 2017-Dec. 2019 PUD • Cumulative risk ratios for PM 2.5 and PM 10 showed nearly linear adverse effect and gently grew to maximums of 2.40 (95% CI: 1.36–4.24) and 1.65 (95% CI: 0.98–2.76), respectively. • Significant associations for both men and women were only observed for PM 2.5 . 59 Yang, Lin, 2020 128 China Smoking Case-Control Study Fujian Province / N = 423 Jan. 2010-Dec. 2016 ECa • Tobacco smoking was related to ESCC risk, but no significant difference in magnitude of its association with respect to macroscopic type of cancer. • Tobacco smoking showed increased risk for ulcerative type ESCC (OR: 2.24; 95% CI: 1.20–4.19) and medullary type ESCC (OR: 2.56; 95% CI: 1.29–5.06). 60 Yang, Chen, 2017 129 China Smoking Case-Control Study Taixing / N = 3314 Oct. 2010-Sept. 2013 ECa • In a fully adjusted analysis, current smokers had OR of 1.12 (0.88–1.44) but not significant. • Male heavy smokers (i.e., smoked more than 20 cigarettes/day or 40 pack-years or started smoking early) showed a moderately increased risk for ESCC. 61 Yates, 2014 130 UK Smoking Cohort Study EPIC-Norfolk Cohort N = 24068 1993–1997 BE/ECa • Hazard ratios for current and former smokers for BE were 1.57 (95% CI: 0.83–2.96) and 1.38 (95% CI: 0.88–2.16), respectively. • Hazard ratios for current and formers smokers for EAC were 1.82 (95% CI: 0.81–4.09) and 1.27 (95% CI: 0.71–2.27), respectively. • Current and former smoking were not significantly associated with BE and EAC. 62 Yu, 2021 131 China PM 2.5 Cross-Sectional Study Zhejiang Province / N = 647,092 Jan. 2014-Dec. 2018 PUD • A potential dose-response relationship was observed between quartile concentrations of PM 2.5 1 month before gastroscopy and detection of PUD. Subjects in the highest quartile of PM 2.5 exposure displayed significantly higher risk (OR: 1.178; 95% CI: 1.118–1.242). • The overall estimated OR for the detection of PUDs associated with a 10 µg/m 3 increase in PM 2.5 was 1.050 (95% CI: 1.038–1.063) 63 Zacharakis, 2023 132 Saudi Arabia Smoking Cohort Study Al-Kharj, Riyadh / N = 1080 Jan. 2017-May 2023 GCa • Current and former smoking yielded ORs of 4.00 (95% CI: 2.05–7.81) and 0.79 (95%. CI: 0.28–2.24), respectively. • Only current smoking was a significant risk factor for GCa (P = 0.002) 64 Zhao, 2017 133 China Smoking Case-Control Study 4 counties Jiangsu Province / N = 18093 Jan. 2003-Dec. 2010 ECa/GCa • Tobacco smoking was associated positively with both esophageal (aOR: 1.68; 95% CI: 1.50–1.87) and stomach cancer (aOR: 1.61; 95% CI: 1.43–1.81). • There was a significant does-response relationship between pack-years of smoking and risks of esophageal (P < 0.001) and stomach cancer (P < 0.001). RESULTS Literature Search. A total of 764 studies were identified from PubMed and reference-list screening, Fig. 1 . After removal of 222 duplicates, 542 articles were screened. Following application of inclusion criteria, 216 articles were excluded and 326 articles were assessed for eligibility based on exclusion criteria. Application of exclusion criteria involved removal of 141 non-original research articles, 85 translational studies, 27 case reports/series, and 9 pediatric studies for a total of 262 articles. N = 64 original research articles were considered eligible and included in this review. Data from screening and extraction are available, Supplemental Tables 1–6. Risk of bias using NOS was assessed in cohort (N = 20), case-control (N = 23), and cross-sectional studies (N = 18), Supplemental Table 7. Two studies that were case-crossover studies and one study that was an ecological study were unable to be assessed for risk of bias as the NOS and our adaptations did not cover for these types of studies. Scores obtained from the NOS were adapted as in previously published studies to reflect the quality of each paper. 69 Cutoffs for each risk of bias assessment depending on article type can be found within the footnote of Supplemental Table 7. Among cohort studies, N = 15 articles were of good quality, N = 1 of fair quality, and N = 4 of poor quality. Among case-control studies, N = 15 were of good quality, N = 5 of fair quality, and N = 3 of poor quality. Among cross-sectional studies, N = 14 were of good quality, N = 2 of satisfactory quality, and N = 2 of unsatisfactory quality. Study Characteristics. The populations of patients with esophageal or gastric disease included those afflicted with esophagitis (n = 8), BE (n = 8), ECa (n = 24), GERD (n = 11), PUD Fig. 1 . Study design per Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Guidelines. PRISMA is an evidence-based minimum set of items for reporting in systematic reviews and meta-analyses. 66,67 (n = 9), and GCa (n = 16). Studies that focused on any other outcomes did not meet exclusion/inclusion criteria. The exposures that were investigated in particular were smoking, waterpipe smoking, and PM 2.5 /PM 10 exposure. While there were no studies that focused on marijuana smoking or vaping/e-cigarettes that met our inclusion/exclusion criteria we know from the literature that use of cannabinoids and vaping are linked to the development of gastrointestinal disorders. 134 One study investigated the role of exposure to second-hand smoke, in addition to direct cigarette smoke exposure. 110 Most studies produced an odds ratio (OR), risk ratio (RR), correlation coefficient (CC), or hazard ratio (HR) to measure each of the risks associated with their respective exposures for a particular outcome, of which are summarized in Fig. 2 (see raw data in Supplemental Table 8A-E ). Among those studies, some reported using adjusted models in their analyses. Additionally, other studies focused on the percent presentation of risk factors; 72,86 risk by measuring the increase in incidence of the respective disease; 91–93,114 the differences in mortality with respect to magnitude of exposure 95 , and utilized a novel predictive model to identify risk factors. 115 Table 1 . Esophagitis. Current tobacco use was identified as a significant risk factor for reflux esophagitis (RE). 73,77,97,104 When studying gender-specific differences between smoking and risk of RE, Kim, Jung, et al found that smoking led to greater risks of RE among women compared to men. 84 Associations between smoking and eosinophilic esophagitis (EE) were also investigated. Some studies found that EE were significantly less likely to have ever smoked cigarettes compared to non-EE controls, but smoking was not significantly associated with increased risk of EE. 74,86 Lee, et al, however, identified smoking as a significant risk factor for asymptomatic EE (AEE). 89 Barrett’s Esophagus. Smoking was identified as a risk factor for BE. 73,97 Schmidt, et al found that BE cases were significantly more likely to smoke. 114 Navab, et al found positive correlation between current and prior tobacco use and BE. 102 Etemadi, et al found associations between smoking and BE that were independent of intensity, age at initiation, and GERD, but dependent on duration and years since cessation. 76 Other studies, however, produced conflicting results: some studies found that current and former smoking were not significantly associated with BE. 75,130 Gastroesophageal Reflux Disease. Multiple studies identified smoking as a risk factor for GERD. 75,78,96,98,113 Kim, Jang, et al interestingly found that former smoking was significantly associated with risk of GERD, while current smoking was not significantly associated. 83 When investigating gender-specific differences on the effects of smoking on the risk of GERD, Kim, Jung, et al found that smoking increased risks in both men and women. 84 One study investigated the effects of waterpipe smoking in addition to traditional cigarette smoking on the risk of GERD. Etemadi, et al found that waterpipe smoking was most strongly associated with “severe and frequent” reflux, and prevalence of the disease was associated with waterpipe use and duration. In addition, they found that cigarette smoking was a significant risk factor of any form of reflux among men. 76 Conversely, some studies noted no significant association between GERD and smoking. Almadi, et al observed a higher prevalence of GERD among smokers than non-smokers, but found no significant difference. 70 Wang, Leena, et al also did not find any association between cigarette smoking and risk of GERD. 123 One study, Seo, et al, developed a prediction model that was significantly able to predict GERD-related medical utilization in the South Korean population and identified PM 2.5 as a risk factor for GERD. 115 Peptic Ulcer Disease. Chuang, et al identified current tobacco use as a significant risk factor for PUD and that higher cumulative amounts of tobacco use were at higher risk for PUD. 73 Further, Begovic, et al found that more than half of ulcer patients enrolled into their study were smokers, and this difference was significant when compared to the those who were non-smokers. 72 Levenstein, et al observed that age-, gender-, and socioeconomic status-adjusted associations were significant for smoking. 90 Park, Kim, Jung, et al investigated the role of changes in smoking status in risk of gastroduodenal ulcer. They observed that changes in smoking status from never smoker, quitter, and current smoker, to current smoker in particular had relatively higher HRs than other groups. When comparing smoking amount levels, they found that smokers who smoked > 20 pack-years had significantly higher risk than lighter smokers. 107 Other studies had investigated the role of PM exposure in risk of PUD. Tsai, et al found that increases in both PM 2.5 and PM 10 were significantly associated with increased risk of PUD hospitalizations on warm days, but only PM 10 was significantly associated on cold days. 122 Similarly, Wong, et al found that PUD hospitalization was associated with 10 ug/m 3 increases in PM 2.5 . When investigating different types of ulcers, they found that associations with PM 2.5 were significant for gastric ulcers, but not for duodenal ulcers. 126 Wu, et al observed that cumulative RRs for PM 2.5 and PM 10 showed nearly linear adverse effects. 127 When looking at gender-adjusted differences, significant associations for men and women were only observed for PM 2.5 . Quan, et al found that when air pollution exposures were assessed over 3-, 5-, and 7-day averages, pollutants were inversely associated with upper gastrointestinal bleeding (UGIB). 109 Yu, et al observed a potential dose-response relationship between quartile concentrations of PM 2.5 one month prior to detection of PUD. Subjects in the highest quartile of PM 2.5 exposure displayed significantly higher risk and the detection of PUD was associated with a 10 ug/m 3 in PM 2.5 . 131 Esophageal Cancer. Many studies found associations between smoking and ECa. 101,116,133 Other studies focused on esophageal squamous cell carcinoma and also identified smoking as a risk factor and this risk increased with tobacco intensity and smoking duration, but no significant difference with respect to macroscopic type of cancer, as smoking showed similarly increased risks for both ulcerative type and medullary type eosinophilic squamous cell carcinoma (ESCC). 81,85,100,117,125,128 Jayalekshmi, et al observed higher risks of ESCC for current bidi and cigarette smokers. 80 Conversely, some studies observed non-significant relationship between inhalational exposures and ECa. 73,105,129 Some studies looked at how smoking affected survival for those afflicted with ECa. Spreafico, et al found that smoking conferred worse overall survival in the combined Boston-Toronto Cohort for each 20 pack-year increase. 119 Other observed how current and former smoking contributed to decreased survival with respect to subtype, specifically ESCC and esophageal adenocarcinoma (EADC). 124,130 One study in particular, Rafiq, et al evaluated both smoking and second-hand smoke as a risk factor for ECa, with increased risks associated with either exposure. 110 Another study, Pan, et al focused on associations between smoking and esophageal precancerous lesions (EPL) and found that consuming more than 30 cigarettes/day or having 40 or more pack-years of cumulative smoking was significantly associated with EPL. 106 Other studies investigated the relationship between PM 2.5 exposure and ECa. Li, Guo, et al observed a significantly positive association between PM 2.5 and ECa incidence. When investigating the corresponding lag effects on ECa incidence, they found that a lag effect of 4 years showed the greatest risk for males and females. 91 Li, Jing, et al examined the modifying effects of urbanization and socioeconomic factors and found a stronger association between PM 2.5 and incidence for low urbanization groups, and this association was stronger for females than males. 92 Li, He, et al identified long-term exposure to black carbon, organic carbon, nitrate, and ammonium to be significantly associated with ECa. 93 Rao, et al found that although spatial distributions of hospitalization rate of ECa in 2016 were not consistent with that of PM 2.5 concentration in the same year, concentrations of PM 2.5 in 2003 and 2004 had the strongest correlations with hospitalization rate in 2016. 112 Sun, et al observed a linear concentration-response relationship between long-term PM 2.5 and ECa. 120 Conversely, Lin, Shih, et al observed that the average number of deaths due to ECa decreases with increasing average PM 2.5 concentration. 95 Gastric Cancer. As with the previous outcomes, most studies identified smoking as a risk factor for GCa. 71,111,132,133 Current cigarette smoking status was found to be attributed to increased risk of GCa and this risk increased among those with longer durations of smoking or later starting ages of smoking. 94 Current smoking was also found to have increased risk of stomach cancer death. 99 When assessing changes in smoking status, one study found that those who changed to their current status to “smoking” showed increased risk of GCa and this risk was the highest in heavier smokers. 108 One study found that smoking was only significantly associated with single GCa and synchronous multiple gastric cancer (SGMCa) in advanced gastric cancer (AGCa) patients. 118 Current smoking also showed increased risk for gastric adenocarcinoma (GAC) and gastric non-cardia adenocarcinoma (GNCA). 124 Interestingly, Jayalekshmi, et al found that bidi smoking was significantly associated with GCa risk, but cigarette smoking was not. This risk increased with the number of bidis smoked daily and with duration of bidi smoking. 79 Conversely, Chuang, et al found that tobacco use was a non-significant risk factor for GCa. 73 Other studies found that current smoking increased risks of intestinal metaplasia for both men and women. Further, this risk increased with increasing duration and total dose. 82,121 Some studies investigated the role of waterpipe smoking in GCa risk. Several studies in Vietnam showed that water pipe smoking was positively associated with GCa risk, but there was no significant interaction between the effects of water pipes and cigarette smoking on GCa risk. 87,88,103 Li, He, et al found that long-term exposure to black carbon, organic carbon, nitrate, ammonium, and sulfate was significantly associated with stomach cancer. 93 DISCUSSION In this systematic review, we investigated the associations between environmental exposures and diseases of the upper gastrointestinal tract. Through a comprehensive review of the available literature, we identified complex relationships between environmental exposures and upper gastrointestinal diseases. Most of the studies showed that exposures including particulate matter, smoking, and waterpipe were significantly associated with higher risk of aerodigestive diseases. Particulate matter (PM) exposure is a global cause of significant pulmonary morbidity and mortality. 6–46 Our review supports existing evidence suggesting that exposure to PM may also increase the risk of diseases affecting the upper gastrointestinal tract. Studies included in this review demonstrated links between PM exposure and an increased risk of ECa and PUD, although the underlying mechanisms remain to be fully explained. These findings highlight the importance of considering environmental factors, such as air pollution, in the context of upper gastrointestinal health. PM consists of various harmful compounds which can trigger inflammatory responses, oxidative stress and DNA damage that contribute to the development of cancer and ulceration. Moreover, studies showed that PM may disrupt the gut microbiota, leading to increased risk of gastrointestinal inflammation and cancers. 135 Cigarette smoking has been recognized as a major risk factor for various cancers, including those of the gastrointestinal tract. Consistent with previous research, our review highlights the detrimental effects of smoking on the upper gastrointestinal tract, with a notable association observed between smoking and an elevated risk of Barrett’s esophagus, GCa, ECa and PUD. The carcinogenic effect of smoking is attributable to mutations in critical genes caused by tobacco metabolites and chemicals. Smoking is also associated with progression, aggressiveness, and reduced survival rates of existing gastrointestinal cancers. Smoking may be associated with exacerbation of GERD symptoms due to reducing esophageal sphincter tone and increasing gastric acid production. 136 Waterpipe smoking has increased worldwide due to a perception that it is less harmful than cigarette smoking. However, waterpipe smoke contains tobacco and several toxicants that may increase the risk of developing aerodigestive disease, as identified in our review. Numerous carcinogens have been identified in waterpipe smoke including polycyclic aromatic hydrocarbons (PAHs), volatile aldehydes, and heavy metals, which can cause DNA damage and develop cancer over time. 137 Moreover, emerging evidence suggests that vaping and marijuana use may also impact gastrointestinal health, although further investigation is warranted to better understand the nature of these associations. Gastrointestinal symptoms associated with vaping can occur in more than half of exposed patients. 138,139 The gastrointestinal symptoms are thought to be directly related to the inhalation of nicotine; users of novel nicotine delivery products (vapers) usually take in higher doses of nicotine than tobacco smokers. 140 Nausea, vomiting, diarrhea and abdominal pain are also signs of with E-cigarette or Vaping Product Use–Associated Lung Injury (EVALI), as indicated in several case reports. 141 In a survey of UK vapers (that met our exclusion criteria), the incidence of the new symptom vomiting amongst “current vapers” was 13.0% and 21% for nausea. Current vapers using cannabinoid-based substances reported nausea significantly more frequently than other groups. Respondents reporting vomiting/nausea were given the diagnosis of gastritis or gastroenteritis. The incidence of nausea and vomiting was not increased in exclusive vapers compared to concurrent smokers and vapers. 142 In tobacco smokers, due to the burning process, nicotine can be transformed into nitrosamines via nitrosation, and many of these nitrosamines, such as nicotine-derived nitrosamine ketone (NNK) and N-nitrosonornicotine (NNN), are potent carcinogens linked to esophageal and stomach cancer. 143,144 Novel delivery devices such as e-cigarettes produce 5% as much nitrosamines compared to standard burning tobacco products, leading to an assumption that e-cigarettes are safer than cigarettes and could be used as cessation aids. However, translational in vitro and murine studies showed that nicotine from e-cigarette induced carcinogenic DNA-adducts and inhibited DNA repair just like nicotine-derived nitrosamine ketone (NNK). Because it often takes over two decades for tobacco smokers to develop cancer, mice were exposed to e-cigarette vapors for one year and had their organs examined. While cancers were detected in the lungs of the mice due to e-cigarette exposure, cell hyperplasia also occurred in the bladder epithelium, raising the possibility that although e-cigarette exposure is inhalational, it can cause systemic cancers. Furthermore, the nicotinic acetylcholine receptor (nAChR), a genetic variant of which is consistently linked to lung cancer in large genetic studies, might mediate carcinogenesis through directly binding nicotine (and nitrosamines) in airway epithelium. This mechanism could provide direct carcinogenesis of nicotine and nicotine-metabolites to all cells that express the nAChR, particularly in carriers of the variants that are associated with tobacco smoking and cancer. 145–148 Following the idea that inhaled nicotine could produce carcinogenic molecules in human users, an untargeted metabolomics analysis of urine demonstrated a trend of increased carcinogen biomarkers in the samples of a relatively small cohort of vapers (n = 34 vs. n = 45 non-users). 149 Limitations While this systematic review provides valuable insights into the associations between environmental exposures and upper gastrointestinal diseases, the included studies vary in design, methodology, and population characteristics, which may introduce heterogeneity and bias. Some studies used adjusted models when calculating ORs or HRs (aOR; aHR). It is possible that these adjustments are complex and vary widely across these studies, further contributing to heterogeneity. Additionally, the majority of studies are observational in nature limiting causal inference and necessitating further research, including prospective cohort studies and mechanistic investigations. This study only relied on the PubMed database for the identification of potentially eligible studies. Our risk of bias assessment (NOS) was able to evaluate the majority but not all studies assessed in this review. Other limitations revolved around how we defined environmental exposure and aerodigestive disease as a whole. Our study defined environmental exposures as air pollution in the form of particulate matter, cigarette/tobacco smoke, marijuana smoke, vape/e-cigarette aerosols. Due to this, it was not possible to completely cover the entire scope of environmental exposures that afflict society. In addition, our definition of aerodigestive disease focused on diseases of the upper gastrointestinal tract, which comprised of esophagitis, Barrett’s esophagus, GERD, PUD, and esophageal/gastric cancer based on the articles we found. It is very likely that there are other aerodigestive diseases that interact strongly with environmental exposures that were not covered by this paper. Due to these definitions and our inclusion/exclusion criteria, we also found no eligible articles that investigated the interactions of marijuana smoke and vape/e-cigarette aerosols with aerodigestive disease. Future Research Currently, there are no human studies available to clearly define the cancer-inducing potential of non-burning nicotine delivery products such as e-cigarettes. However, this could be due to the very extensive lag time between carcinogen exposure and clinical cancer diagnosis in humans. Future studies could expand our definitions to account for interactions not present within this review, such as those of marijuana smoking, vaping, and those of the lower intestinal tract. Additionally, future studies could assess the contribution of specific occupational exposures to aerodigestive health, as this study only focused on exposures commonly experienced by the general population. Such additional exposures include asbestos, synthetic fiber dust, chrysotile dust, nephrite, and potentially harmful elements (PHEs) which are all commonly present in mining or textile industries and in developing societies in general. Such investigations could yield valuable insights for those whose occupation or geographic location puts them at risk for such diseases, as aerodigestive disease is often not recognized for those working/living under such conditions. In addition, this could identify how specific exposures incite disease in various cohorts. Conclusion The implications of these findings are significant from both a public health and clinical perspective. Efforts to reduce exposure to environmental pollutants, such as particular matter, could potentially mitigate the burden of upper gastrointestinal diseases in affected populations. Similarly, targeted interventions aimed at reducing smoking behavior and promoting smoking cessation may help reduce the incidence of BE and malignancy. Furthermore, continued research into the potential health effects of emerging trends, such as vaping and marijuana use, is crucial for informing preventive strategies and improving patient outcomes. This review provides support for the connection between environmental exposures and digestive health, which is especially important considering that those who have been exposed to environmental/occupational inhalants are generally not covered for their digestive health. We hope that this review will promote further recognition of treatment of digestive disease with inhalational exposure. In conclusion, this systematic review contributes to our understanding of the interplay between exposure to inhalational exposures and diseases of the upper gastrointestinal tract. By synthesizing existing evidence and identifying knowledge gaps, this study highlights the need for approaches to address environmental risk factors and promote gastrointestinal health. Abbreviation AEE Asymptomatic Erosive Esophagitis AGCa Advanced Gastric Cancer AHR Airway Hyperreactivity aOR Adjusted Odds Ratio BE Barrett’s Esophagus Ca Cancer CC Correlation Coefficient CI Confidence Interval E Esophagitis EAC Esophageal Adenocarcinoma ECa Esophageal Cancer EE Eosinophilic Esophagitis EPL Esophageal Precancerous Lesions ESCC Esophageal Squamous Cell Carcinoma GAC Gastric Adenocarcinoma GERD Gastroesophageal Reflux Disease GCa Gastric Cancer GNCA Gastric Non-Cardia Adenocarcinoma HR Hazard Ratio NOS New-Castle Ottawa Scale OAD Obstructive Airway Disease OR Odds Ratio PAH Polycyclic Aromatic Hydrocarbons PEO Population, Exposure, Outcome PHE Potentially Harmful Elements PM Particulate Matter PUD Peptic Ulcer Disease RE Reflux Esophagitis RR Risk Ratio SGMCa Synchronous Multiple Gastric Cancer SHS Second-Hand Smoke UGIB Upper Gastrointestinal Bleeding WHO World Health Organization WPT Waterpipe Tobacco WTC World Trade Center Declarations Data Availability All data generated or analyzed during this study are included in this published article and its supplementary information files. Funding Sources: This work was supported by CDC/NIOSH U01 -OH012069; -OH011855; -OH011300 (AN); NIH NCATS: UL1TR001445; KL2TR001446 (SK); Stony Wold-Herbert Fund (SK); NIH NIEHS: 1L70HL170444-01 (SK); NIH NIEHS R01ES032808 (ML). Acknowledgements We would like to acknowledge the World Trade Center Health Program and World Trade Center-Exposed 9/11 rescue workers. Author Information Authors and Affiliations Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, New York University Grossman School of Medicine (NYUGSoM); New York (NY), NY, USA Daniel Hyun Kim, Sanjiti Podury, Aida Fallah Zadeh, Sophia Kwon, Anna Nolan Department of Medicine, Division of Environmental Medicine, NYUGSoM, NY, NY, USA Gabrielle Grunig, Anna Nolan Department of Population Health, Division of Biostatistics; NYUGSoM, NY, NY, USA Mengling Liu Contributions DHK, SP, and AN conceived and planned the systematic review. DHK and SP carried out the literature search. 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C., Huang, W. C. & Lepor, H. Electronic-cigarette smoke induces lung adenocarcinoma and bladder urothelial hyperplasia in mice. Proc Natl Acad Sci U S A 2019, 116 , 21727-21731, doi:10.1073/pnas.1911321116. Young, R. P., Hopkins, R. J., Hay, B. A., Epton, M. J., Black, P. N. & Gamble, G. D. Lung cancer gene associated with COPD: triple whammy or possible confounding effect? Eur Respir J 2008, 32 , 1158-1164, doi:10.1183/09031936.00093908. Young, R. P. & Scott, R. J. Inhaled nicotine and lung cancer: Potential role of the nicotinic acetylcholine receptor. Proc Natl Acad Sci U S A 2020, 117 , 4460-4461, doi:10.1073/pnas.1921567117. Tang, M. S. Reply to Young and Scott: Nicotine and nicotinic acetylcholine receptor mutations in electronic-cigarette smoke lung carcinogenicity. Proc Natl Acad Sci U S A 2020, 117 , 4462-4463, doi:10.1073/pnas.1922490117. Tang, M. S., Lee, H. W., Weng, M. W., Wang, H. T., Hu, Y., Chen, L. C., Park, S. H., Chan, H. W., Xu, J., Wu, X. R., Wang, H., Yang, R., Galdane, K., Jackson, K., Chu, A. & Halzack, E. DNA damage, DNA repair and carcinogenicity: Tobacco smoke versus electronic cigarette aerosol. Mutat Res Rev Mutat Res 2022, 789 , 108409, doi:10.1016/j.mrrev.2021.108409. Hsiao, Y. C., Matulewicz, R. S., Sherman, S. E., Jaspers, I., Weitzman, M. L., Gordon, T., Liu, C. W., Yang, Y., Lu, K. & Bjurlin, M. A. Untargeted Metabolomics to Characterize the Urinary Chemical Landscape of E-Cigarette Users. Chem Res Toxicol 2023, 36 , 630-642, doi:10.1021/acs.chemrestox.2c00346. Additional Declarations No competing interests reported. Supplementary Files SUPPLEMENTALTABLESlegends.docx 06SupplementalTable1UniqueNoDupes.docx 07SupplementalTable2didntMeetInclusion.docx 08SupplementalTable3Nonoriginal.docx 09SupplementalTable4translational.docx 10SupplementalTable5CaseReports.docx 11SupplementalTable6Pediatric.docx 12SupplementalTable7RoB.docx 13SupplementalTable8RawDataSets.docx Cite Share Download PDF Status: Published Journal Publication published 02 Jul, 2025 Read the published version in Scientific Reports → Version 1 posted Editorial decision: Revision requested 23 Aug, 2024 Reviews received at journal 22 Aug, 2024 Reviews received at journal 17 Aug, 2024 Reviews received at journal 11 Aug, 2024 Reviewers agreed at journal 11 Aug, 2024 Reviewers agreed at journal 11 Aug, 2024 Reviewers agreed at journal 10 Aug, 2024 Reviewers invited by journal 29 Jul, 2024 Editor assigned by journal 29 Jul, 2024 Editor invited by journal 11 Jul, 2024 Submission checks completed at journal 08 Jul, 2024 First submitted to journal 27 Jun, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4650430","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":333766861,"identity":"1948d53a-ddd4-4a49-9f61-0b9784844fae","order_by":0,"name":"Daniel Hyun Kim","email":"","orcid":"","institution":"Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, New York University Grossman School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Daniel","middleName":"Hyun","lastName":"Kim","suffix":""},{"id":333766862,"identity":"2ecbfe73-63d4-4561-b13c-bcb6a75a37a2","order_by":1,"name":"Sanjiti Podury","email":"","orcid":"","institution":"Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, New York University Grossman School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Sanjiti","middleName":"","lastName":"Podury","suffix":""},{"id":333766863,"identity":"25423a9c-3366-4b39-a71e-568624218e88","order_by":2,"name":"Aida Fallah Zadeh","email":"","orcid":"","institution":"Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, New York University Grossman School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Aida","middleName":"Fallah","lastName":"Zadeh","suffix":""},{"id":333766864,"identity":"7caf5749-ae9b-4a28-83db-74cecdb3191d","order_by":3,"name":"Sophia Kwon","email":"","orcid":"","institution":"Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, New York University Grossman School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Sophia","middleName":"","lastName":"Kwon","suffix":""},{"id":333766865,"identity":"240e4c2e-027d-4256-9ea1-5bd39bc7549c","order_by":4,"name":"Gabriele Grunig","email":"","orcid":"","institution":"Department of Medicine, Division of Environmental Science, New York University Grossman School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Gabriele","middleName":"","lastName":"Grunig","suffix":""},{"id":333766869,"identity":"cb6ed348-16d5-4dbe-97df-d3ff62be9e73","order_by":5,"name":"Mengling Liu","email":"","orcid":"","institution":"Department of Population Health, Division of Biostatistics, New York University Grossman School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Mengling","middleName":"","lastName":"Liu","suffix":""},{"id":333766871,"identity":"2e4ef3b2-c73a-45ec-8143-fb3bc618e864","order_by":6,"name":"Anna Nolan","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABEklEQVRIiWNgGAWjYBADGQYG5gNA2oJ4LTwMDGwJQFqCJC08BsRp4Z/de/AD4w4bHv7ZPd8e87ZJyJvzLz724AODTb68A3YtEnfOJUswnknjkbhzdrsxUIvhzhnP0g1nMKRZbjyAw5obOQYSjG2HeRhu5G6TBmph3HDjjJk0D8NhA8MG7Drkb+QY/wBpATKegbTYg7X8waPF4EaOGdgWIIMNpCVxw/keM2kGoBZ5HO4yBGqxSGxL4zG8kWYmOeecRPKGG2xpkj0GaQYGOLTIAR1242ObjZzcjeRnEm/KbGw3nD98TOJHhY2BPA6HgUEClGbiAZESIC7QCoMDeLTAAOMPEMkPVYrXllEwCkbBKBhJAAC22ldEpWEbewAAAABJRU5ErkJggg==","orcid":"","institution":"Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, New York University Grossman School of Medicine","correspondingAuthor":true,"prefix":"","firstName":"Anna","middleName":"","lastName":"Nolan","suffix":""}],"badges":[],"createdAt":"2024-06-27 17:42:56","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4650430/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4650430/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41598-025-06620-7","type":"published","date":"2025-07-02T15:57:50+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":61483754,"identity":"60a516bc-08c2-4762-ab5e-2fd1e320d4ca","added_by":"auto","created_at":"2024-07-31 09:18:17","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":150565,"visible":true,"origin":"","legend":"\u003cp\u003eStudy design per Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Guidelines. PRISMA is an evidence-based minimum set of items for reporting in systematic reviews and meta-analyses.\u003csup\u003e66,67\u003c/sup\u003e\u003c/p\u003e","description":"","filename":"03Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-4650430/v1/a0341954db7f6572e13c0fbe.png"},{"id":61484536,"identity":"b3c8ae88-6f07-47c7-9a7b-7e818858b3e2","added_by":"auto","created_at":"2024-07-31 09:26:17","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":432244,"visible":true,"origin":"","legend":"\u003cp\u003eOverview of Data Synthesis: (\u003cstrong\u003eA\u003c/strong\u003e) Summary of odds ratios for esophageal diseases (esophagitis, BE, ECa), (\u003cstrong\u003eB\u003c/strong\u003e) Summary of odds ratios for gastric diseases (GERD, PUD, GCa), (\u003cstrong\u003eC\u003c/strong\u003e) Summary of risk ratios, (\u003cstrong\u003eD\u003c/strong\u003e) Summary of correlation coefficients, (\u003cstrong\u003eE\u003c/strong\u003e) 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09:18:17","extension":"docx","order_by":7,"title":"","display":"","copyAsset":false,"role":"supplement","size":15814,"visible":true,"origin":"","legend":"","description":"","filename":"11SupplementalTable6Pediatric.docx","url":"https://assets-eu.researchsquare.com/files/rs-4650430/v1/e6f378d20e50ea58d3ae2e0b.docx"},{"id":61483763,"identity":"0d0748b2-db97-4d38-9f6e-abeb9a77d064","added_by":"auto","created_at":"2024-07-31 09:18:17","extension":"docx","order_by":8,"title":"","display":"","copyAsset":false,"role":"supplement","size":26727,"visible":true,"origin":"","legend":"","description":"","filename":"12SupplementalTable7RoB.docx","url":"https://assets-eu.researchsquare.com/files/rs-4650430/v1/bfea25ff858a3667ca8f9139.docx"},{"id":61483764,"identity":"c9e89043-6525-40c7-be12-a7da2c3e2262","added_by":"auto","created_at":"2024-07-31 09:18:17","extension":"docx","order_by":9,"title":"","display":"","copyAsset":false,"role":"supplement","size":22002,"visible":true,"origin":"","legend":"","description":"","filename":"13SupplementalTable8RawDataSets.docx","url":"https://assets-eu.researchsquare.com/files/rs-4650430/v1/bcf740a11060a3d9118d0967.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Gastroesophageal Disease and Environmental Exposure: A Systematic Review","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eExposome-associated morbidity and mortality is a global health concern. Environmental exposures that individuals encounter over their lifetimes include air pollution, water pollution, diet, and radiation. The exposome\u0026rsquo;s rate, volume, and variety have been linked to heterogenous negative health effects, but mechanisms remain elusive in many disease states. Studying the exposome provides valuable insights into the interplay between environmental factors and human health.\u003csup\u003e1\u003c/sup\u003e Of the various environmental exposures, inhalational exposure has been of great interest, especially in the context of rising levels of global air pollution due to global warming, wildfires, wars, and population growth.\u003c/p\u003e \u003cp\u003eStudies investigating the link between environmental exposures and disease have the potential to impact millions globally. Air pollution is associated with 7-million premature deaths annually, and levels have steadily risen over the past few decades.\u003csup\u003e2\u0026ndash;3\u003c/sup\u003e Over half of the world\u0026rsquo;s population are exposed to levels of air pollution that are substantially above the WHO Air Quality Guidelines.\u003csup\u003e4\u003c/sup\u003e There are a greater proportion of non-communicable disease attributable to environmental exposure in developing countries that utilize industrial production factories, primary contributors to emissions.\u003csup\u003e5\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eParticulate matter (PM) exposure, in particular, is a global cause of significant aerodigestive morbidity and mortality.\u003csup\u003e6\u0026ndash;46\u003c/sup\u003e The destruction of the World Trade Center (WTC) on September 11, 2001 (9/11) led to intense PM exposure of first responders and inhabitants of New York City (NYC).\u003csup\u003e15\u0026ndash;46\u003c/sup\u003e WTC-PM exposure is associated with obstructive airways disease (OAD). PM was also found to have associations with gastroesophageal diseases, such as gastroesophageal reflux disease (GERD) and Barrett\u0026rsquo;s Esophagus (BE).\u003csup\u003e47\u0026ndash;49\u003c/sup\u003e Approximately 44% of WTC rescue/recovery workers had developed GERD symptoms by 2005.\u003csup\u003e50\u003c/sup\u003e In contrast, GERD has a prevalence of 20% in the US.\u003csup\u003e51\u0026ndash;53\u003c/sup\u003e There is also evidence of comorbid GERD and OAD, as WTC-exposed firefighters with OAD had 3-fold higher risk of developing GERD.\u003csup\u003e49,54\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eGERD is the most prevalent gastrointestinal disorder affecting at least 20% of the US population, and leading to substantial morbidity.\u003csup\u003e55\u003c/sup\u003e Globally, GERD prevalence is 10\u0026ndash;25%.\u003csup\u003e55,56\u003c/sup\u003e Aerodigestive complications also include BE, and malignancy such as esophageal adenocarcinoma (EAC).\u003csup\u003e15,57,58\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eAerodigestive disease can also induce or worsen respiratory disease such as airway hyperreactivity (AHR). This may be explained by the clearing mechanism of the respiratory system and its close proximity to the digestive system at the pharynx. However, this is an area of active investigation.\u003csup\u003e59\u003c/sup\u003e Prior systematic reviews on the topic have only focused on single inhalational exposures and/or single diseases/outcomes.\u003csup\u003e60\u0026ndash;65\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eOur systematic review focuses on the exposome in a more holistic manner in order to assess its effects on the scope of gastroesophageal diseases on a greater scale. We investigated the associations between exposure (particulate matter, smoking, waterpipe smoking) with diseases of the upper gastrointestinal tract (GERD, Barrett\u0026rsquo;s and malignancy).\u003c/p\u003e"},{"header":"METHODS","content":"\u003cp\u003e\u003cstrong\u003eReview Strategy.\u003c/strong\u003e Our systematic review adhered to the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines.\u003csup\u003e66,67\u003c/sup\u003e Our Population, Exposure, Outcome \u003cstrong\u003e(PEO)\u003c/strong\u003e question was to investigate among adult populations \u003cstrong\u003e(P)\u003c/strong\u003e, whether there is an association between inhalational exposure (e.g., air pollution, cigarette/tobacco smoke, marijuana smoke, vape/e-cigarette aerosols) \u003cstrong\u003e(E)\u003c/strong\u003e and esophageal or gastric disorders/disease \u003cstrong\u003e(O)\u003c/strong\u003e.\u003c/p\u003e\n\u003cp\u003ePubMed searches were conducted on May 1, 2024 as per the protocol of our systematic review registered on PROSPERO on April 29, 2024 and can be accessed at Prospero ID 536834. The following \u003cstrong\u003eMeSH Terms\u003c/strong\u003e were searched for using the MeSH Database:\u003c/p\u003e\n\u003ctable\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd\u003e(\u0026quot;Particulate Matter\u0026quot;[Mesh]) OR (\u0026quot;Vaping\u0026quot;[Mesh]) OR (\u0026quot;Smoking\u0026quot;[Mesh]) OR (\u0026quot;Smoking Devices\u0026quot;[Mesh]) OR (\u0026quot;Tobacco Use\u0026quot;[Mesh]) OR (\u0026quot;Tobacco Use Cessation Devices\u0026quot;[Mesh]) OR (\u0026quot;Electronic Nicotine Delivery Systems\u0026quot;[Mesh]) OR (\u0026quot;E-Cigarette Vapor\u0026quot;[Mesh]) OR (\u0026quot;Inhalant Abuse\u0026quot;[Mesh]) OR (\u0026quot;Marijuana Smoking\u0026quot;[Mesh]) OR (\u0026quot;Marijuana Use\u0026quot;[Mesh]) OR (\u0026quot;Marijuana Abuse\u0026quot;[Mesh]) OR (\u0026quot;Cannabis\u0026quot;[Mesh]) OR (\u0026quot;Cannabinoids\u0026quot;[Mesh])\u003cbr\u003e\n \u003ch2\u003e[AND]\u003c/h2\u003e\n \u003cp\u003e(\u0026ldquo;Stomach Diseases\u0026rdquo;[Mesh]) OR (\u0026ldquo;Esophageal Diseases\u0026rdquo;[Mesh])\u003c/p\u003e\u003cbr\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eThe complete listing of associated terms that were searched for with each of the above Mesh terms, can be found at MeSH Database. For example, when searching for \u0026ldquo;stomach diseases\u0026rdquo; under its associated Mesh term, we were able to search for Reflux, Gastritis, Peptic Ulcer, Stomach Neoplasms, Zollinger-Ellison syndrome, etc. Reference-list screening was also used.\u003c/p\u003e\n\u003cp\u003eFor this review, we have defined environmental exposure to include PM\u003csub\u003e2.5\u003c/sub\u003e, PM\u003csub\u003e10\u003c/sub\u003e, tobacco/cigarette smoke, vape/e-cigarette aerosols, and marijuana/cannabinoid inhalation. We have defined esophageal and gastric disease to include the following: gastroesophageal reflux disease (GERD), Barrett\u0026rsquo;s Esophagus (BE), peptic ulcer disease (PUD), esophagitis, gastritis, esophageal cancer, and stomach cancer.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy Criteria.\u003c/strong\u003e Studies were included if they \u003cstrong\u003e(1)\u003c/strong\u003e discussed the environmental/occupational exposure to inhalants, specifically, PM\u003csub\u003e2.5\u003c/sub\u003e, PM\u003csub\u003e10\u003c/sub\u003e, tobacco/cigarette smoke, marijuana smoke, and/or vape/e-cigarette vapor, \u003cstrong\u003e(2)\u003c/strong\u003e evaluated effects of exposures on esophageal or gastric diseases, \u003cstrong\u003e(3)\u003c/strong\u003e performed on adult human subjects, \u003cstrong\u003e(4)\u003c/strong\u003e were written in English, and \u003cstrong\u003e(5)\u003c/strong\u003e were published within the last 10 years.\u003c/p\u003e\n\u003cp\u003eStudies were excluded if they \u003cstrong\u003e(1)\u003c/strong\u003e were not original research, \u003cstrong\u003e(2)\u003c/strong\u003e consisted of translational research, \u003cstrong\u003e(3)\u003c/strong\u003e were case reports or series, or \u003cstrong\u003e(4)\u003c/strong\u003e were conducted on a pediatric population.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Extraction.\u003c/strong\u003e Articles were reviewed and data regarding study design, patient characteristics, sample size, and tool used were extracted. Results from database searches were filtered for full-text articles, human subjects, English language, and publication date and imported into Endnote X9. Original research papers were reviewed for (title, abstract, and full text) to ascertain eligibility. We examined references cited in the relevant articles. All results were screened by DHK and SP and further independently evaluated by AN. Disagreements were resolved by consensus.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRisk of Bias Assessment.\u003c/strong\u003e Systematic review inherent bias (selection, detection, performance, and reporting) was addressed through study design/search algorithm. Selection bias was addressed by having pre-determined inclusion, exclusion criteria and distinct definitions. Detection and performance bias were addressed by having at least two rounds of screening individually performed by DHK and SP. Reporting bias was minimized by using PubMed search filters for peer-reviewed published articles of human subjects written in English and removing duplicates.\u003c/p\u003e\n\u003cp\u003eThe Newcastle-Ottawa Scale (NOS), a domain-based approach was used to assess the degree of bias.\u003csup\u003e68\u003c/sup\u003e Scales adapted for case-control and cross-sectional studies were used. Total scores obtained by the scale were converted to AHRQ standards or as done in previous studies to reflect the quality of each paper: \u0026ldquo;good\u0026rdquo; (green), \u0026ldquo;fair\u0026rdquo; or \u0026ldquo;satisfactory\u0026rdquo; (yellow), and \u0026ldquo;poor\u0026rdquo; or \u0026ldquo;unsatisfactory\u0026rdquo; (red).\u003csup\u003e69\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics Approval.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study does not require ethical approval as it involves a review of publicly available research and utilized anonymized original data.\u003c/p\u003e\n\u003cdiv\u003e \u0026nbsp;\u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 1\u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003eStudy Characteristics\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eStudy\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCountry\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eExposure/\u003c/p\u003e\n \u003cp\u003eDesign\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eStudy Size/\u003c/p\u003e\n \u003cp\u003eTime Period\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eOutcome\u003c/p\u003e\n \u003cp\u003eof Interest\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eRelevant Findings\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eAlmadi, 2014\u003c/strong\u003e \u003csup\u003e\u003cstrong\u003e70\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSaudi Arabia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmoking\u003c/p\u003e\n \u003cp\u003eCohort Study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4 shopping centers,\u003c/p\u003e\n \u003cp\u003eRiyadh / N\u0026thinsp;=\u0026thinsp;1,265\u003c/p\u003e\n \u003cp\u003eDec. 2012-Jan. 2013\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eGERD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026bull; Higher prevalence of GERD in smokers (51.63% vs. 44.41%), but not significant (p\u0026thinsp;=\u0026thinsp;0.09)\u003c/p\u003e\n \u003cp\u003e\u0026bull; No significant association between GERD and smoking (OR: 1.34; 95% CI: 0.95\u0026ndash;1.87)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eBaroudi, 2014\u003c/strong\u003e \u003csup\u003e\u003cstrong\u003e71\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTunisia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmoking\u003c/p\u003e\n \u003cp\u003eCase-Control Study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSalah Azaiez Insititue of Oncology\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;348\u003c/p\u003e\n \u003cp\u003e2009\u0026ndash;2010\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eGCa\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026bull; Smoking more than 10 cigarettes a day is significantly associated with an increased risk in gastric cancer (OR: 3.66; 95% CI: 1.82\u0026ndash;7.78).\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eBegovic, 2015\u003c/strong\u003e \u003csup\u003e\u003cstrong\u003e72\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNorth Macedonia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmoking\u003c/p\u003e\n \u003cp\u003eCohort Study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 University Clinics /\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;67\u003c/p\u003e\n \u003cp\u003e2014\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003ePUD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026bull; Smoking is an important risk factor and more than half of ulcer patients were smokers (65.75%).\u003c/p\u003e\n \u003cp\u003e\u0026bull; Percent difference in relation to those who are non-smokers is statistically significant (p\u0026thinsp;=\u0026thinsp;0.0000).\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eChuang, 2019\u003c/strong\u003e \u003csup\u003e\u003cstrong\u003e73\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTaiwan\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmoking\u003c/p\u003e\n \u003cp\u003eCross-Sectional Study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4 hospitals in SW Taiwan /\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;8,135\u003c/p\u003e\n \u003cp\u003eApr. 2008-Dec. 2013\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eE / BE / ECa / PUD / GCa\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026bull; Current tobacco use was a significant risk factor for RE (aOR: 1.26; 95% CI: 1.09\u0026ndash;1.46), BE (aOR: 1.47; 95% CI: 1.08-2.00) and PUD (1.79; 95% CI: 1.52\u0026ndash;2.10), but nonsignificant for ESCC (aOR: 1.40; 95% CI: 0.57\u0026ndash;3.43) and GC (aOR: 1.24; 95% CI: 0.53\u0026ndash;2.91).\u003c/p\u003e\n \u003cp\u003e\u0026bull; Higher cumulative amounts of tobacco use were at higher risk for PUD (aOR: 1.92; 95% CI: 1.60\u0026ndash;2.31)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eCrews, 2016\u003c/strong\u003e \u003csup\u003e\u003cstrong\u003e74\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmoking\u003c/p\u003e\n \u003cp\u003eCohort Study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOlmsted County, MN\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;205\u003c/p\u003e\n \u003cp\u003eApr. 2011-Oct. 2013\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eE / BE\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026bull; In a univariate analysis, ever tobacco use was not a significant risk factor for EE/BE (OR: 0.9; 95% CI: 0.5\u0026ndash;1.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eDore, 2016\u003c/strong\u003e \u003csup\u003e\u003cstrong\u003e75\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eItaly\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmoking\u003c/p\u003e\n \u003cp\u003eCohort Study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSassari, Sardinia /\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;5156\u003c/p\u003e\n \u003cp\u003eJan. 2002-Dec. 2013\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eBE / GERD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026bull; Adjusted ORs of BE and GERD for current smokers were 0.447 (95% CI; 0.199\u0026ndash;1.002) and 1.392 (95% CI: 1.085\u0026ndash;1.787), respectively.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eEtemadi, 2017\u003c/strong\u003e \u003csup\u003e\u003cstrong\u003e76\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIran\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmoking / Waterpipe Smoking\u003c/p\u003e\n \u003cp\u003eCohort Study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eValashahr, Fars /\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;9264\u003c/p\u003e\n \u003cp\u003e2012\u0026ndash;2017\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eGERD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026bull; Strongest associations of waterpipe smoking were with \u0026lsquo;severe and frequent reflux\u0026rsquo; (OR: 1.30; 95% CI: 1.08\u0026ndash;1.56)\u003c/p\u003e\n \u003cp\u003e\u0026bull; Former use had a stronger association with \u0026lsquo;severe reflux\u0026rsquo; and (OR: 1.29; 95% CI: 1.06\u0026ndash;1.56) and current use with \u0026lsquo;frequent reflux\u0026rsquo; (OR: 1.18; 95% CI: 1.03\u0026ndash;1.36).\u003c/p\u003e\n \u003cp\u003e\u0026bull; Current cigarette use was a significant risk factor for \u0026ldquo;any reflux\u0026rdquo; among men (OR: 1.20; 95% CI: 1.02\u0026ndash;1.40)\u003c/p\u003e\n \u003cp\u003e\u0026bull; Increases in reflux prevalence associated with waterpipe use duration and intensity.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eFiliberti, 2015\u003c/strong\u003e \u003csup\u003e\u003cstrong\u003e77\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eItaly\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmoking\u003c/p\u003e\n \u003cp\u003eCase-Control Study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12 endoscopic units\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;1420\u003c/p\u003e\n \u003cp\u003eMar. 2009-Oct. 2012\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eE / BE\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026bull; Associations shown between smoking and BE that was independent of intensity, age at initiation, GERD and dependent of duration and years since cessation\u003c/p\u003e\n \u003cp\u003e\u0026bull; Among current smokers who smoke\u0026thinsp;\u0026gt;\u0026thinsp;18 cigarettes/day, ORs for RE and BE were 1.31 (95% CI: 0.80\u0026ndash;2.17) and 1.86 (95% CI: 0.98\u0026ndash;3.16), respectively.\u003c/p\u003e\n \u003cp\u003e\u0026bull; Risk of BE significantly increased for those who had smoked for \u0026gt;\u0026thinsp;32 years (OR: 2.44; 95% CI; 1.33\u0026ndash;4.45) and those whom\u0026thinsp;\u0026lt;\u0026thinsp;9 years have passed since quitting (OR: 2.11; 95% CI: 1.19\u0026ndash;3.72)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eGhoshal, 2017\u003c/strong\u003e \u003csup\u003e\u003cstrong\u003e78\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIndia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmoking\u003c/p\u003e\n \u003cp\u003eCross-Sectional Study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUttar Pradesh, Jaunpur District /\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;2876\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eGERD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026bull; On univariate analysis, tobacco smoking (105 [35.2%] vs. 672 [27.1%]) was associated with GERD.\u003c/p\u003e\n \u003cp\u003e\u0026bull; On multivariate analysis, tobacco smoking (OR: 1.36; 95% CI: 0.99\u0026ndash;1.88) was associated with GERD\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eJayalekshmi, 2015\u003c/strong\u003e \u003csup\u003e\u003cstrong\u003e79\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIndia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmoking\u003c/p\u003e\n \u003cp\u003eCohort Study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eKarunagappally Cohort, Kerala /\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;65553 men\u003c/p\u003e\n \u003cp\u003e1990\u0026ndash;2009\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eGCa\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026bull; Bidi smoking was significantly associated with GCa risk (RR: 1.6; 95% CI: 1.0-2.5; P\u0026thinsp;=\u0026thinsp;0.042), but cigarette smoking was not (RR: 0.8; 95% CI: 0.5\u0026ndash;1.2)\u003c/p\u003e\n \u003cp\u003e\u0026bull; Bidi smoking increased risk of GCa among never cigarette smokers (RR: 2.2, 95% CI: 1.3-4.0)\u003c/p\u003e\n \u003cp\u003e\u0026bull; GCa risk increased with the number of bidis smoked daily (P\u0026thinsp;=\u0026thinsp;0.012) and with duration of bidi smoking (P\u0026thinsp;=\u0026thinsp;0.036)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eJayalekshmi, 2021\u003c/strong\u003e \u003csup\u003e\u003cstrong\u003e80\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIndia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmoking\u003c/p\u003e\n \u003cp\u003eCohort Study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eKarunagappally Cohort, Kerala /\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;65528 men\u003c/p\u003e\n \u003cp\u003eJan. 1990-Dec. 2013\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eECa\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026bull; RRs for current bidi and cigarette smokers were 1.4 (95% CI: 0.98\u0026ndash;2.12) and 1.3 (95% CI: 0.9\u0026ndash;1.8), respectively.\u003c/p\u003e\n \u003cp\u003e\u0026bull; Higher risks for ESCC observed for current bidi smokers (RR: 2.2; 95% CI: 1.3\u0026ndash;3.8) and cigarette smokers (RR: 1.6; 95% CI: 1.0-2.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eKayamba, 2015\u003c/strong\u003e \u003csup\u003e\u003cstrong\u003e81\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eZambia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmoking\u003c/p\u003e\n \u003cp\u003eCase-Control Study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUniversity Teaching Hospital, Lusaka / N\u0026thinsp;=\u0026thinsp;100\u003c/p\u003e\n \u003cp\u003eOct. 2013-May 2014\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eECa (ESCC)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026bull; Ever smokers showed greater risk of developing ESCC (OR: 8.0; 95% CI: 2.8\u0026ndash;22.7)\u003c/p\u003e\n \u003cp\u003e\u0026bull; Much greater proportion of cases than controls (38% vs 0%) were current smokers (p\u0026thinsp;\u0026lt;\u0026thinsp;0.000)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eKim, Chang, 2019\u003c/strong\u003e \u003csup\u003e\u003cstrong\u003e82\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSouth Korea\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmoking\u003c/p\u003e\n \u003cp\u003eCohort Study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eKangbuk Samsung Hospital, Seoul /\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;199235\u003c/p\u003e\n \u003cp\u003eJan. 2011-Dec. 2017\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eGCa (IM)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026bull; For current smokers, the multivariable-adjusted HR for men and women were 1.51 (95% CI: 1.41\u0026ndash;1.61) and 0.94 (0.73\u0026ndash;1.22), respectively.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eKim, Jang, 2018\u003c/strong\u003e \u003csup\u003e\u003cstrong\u003e83\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSouth Korea\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmoking\u003c/p\u003e\n \u003cp\u003eCohort Study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;2368\u003c/p\u003e\n \u003cp\u003eMar. 2013-Dec. 2015\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eGERD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026bull; Former smokers showed a significantly greater risk of GERD (OR: 1.93; 95% CI: 1.12\u0026ndash;3.35).\u003c/p\u003e\n \u003cp\u003e\u0026bull; Current smokers showed a non-significantly greater risk of GERD (OR: 2.31; 95% CI: 0.94\u0026ndash;5.66).\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eKim, Jung, 2019\u003c/strong\u003e \u003csup\u003e\u003cstrong\u003e84\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSouth Korea\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmoking\u003c/p\u003e\n \u003cp\u003eCross-Sectional Study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEwha Womans University Mokdong Hospital / N\u0026thinsp;=\u0026thinsp;10158\u003c/p\u003e\n \u003cp\u003eJan. 2015-Dec. 2016\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eE / GERD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026bull; Among men, smokers yielded ORs for RE and GERD of 1.67 (95% CI: 1.30\u0026ndash;2.16) and 1.48 (95% CI: 0.85\u0026ndash;2.57), respectively.\u003c/p\u003e\n \u003cp\u003e\u0026bull; Among women, smokers yielded ORs for RE and GERD of 3.47 (95% CI: 1.61\u0026ndash;7.48) and 1.35 (95% CI: 0.68\u0026ndash;2.67), respectively.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eKoca, 2015\u003c/strong\u003e \u003csup\u003e\u003cstrong\u003e85\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTurkey\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmoking\u003c/p\u003e\n \u003cp\u003eCase-Control Study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eErzurum Regional Training and Research Hospital, Anatolia / N\u0026thinsp;=\u0026thinsp;408\u003c/p\u003e\n \u003cp\u003eJan. 2008-Mar. 2014\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eECa\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026bull; Smoking (X\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;7.629; p\u0026thinsp;=\u0026thinsp;0.022) was significantly higher in the patient group than the control group.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eKoutlas, 2018\u003c/strong\u003e \u003csup\u003e\u003cstrong\u003e86\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmoking\u003c/p\u003e\n \u003cp\u003eCase-Control Study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUniversity of North Carolina /\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;340\u003c/p\u003e\n \u003cp\u003e2011\u0026ndash;2015\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eE\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026bull; EE cases were less likely to have ever smoked cigarettes compared to endoscopy-based non-EE controls (23% vs. 47%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\n \u003cp\u003e\u0026bull; aOR for ever-smoking was 0.47 (95% CI: 0.17\u0026ndash;0.76).\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eLai, 2016\u003c/strong\u003e \u003csup\u003e\u003cstrong\u003e87\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eVietnam\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmoking / Waterpipe Smoking\u003c/p\u003e\n \u003cp\u003eCase-Control Study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 major hospitals, Hanoi /\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;1082\u003c/p\u003e\n \u003cp\u003eFeb. 2003-Apr. 2011\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eGCa\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026bull; WPT smoking was positively associated with GCa risk. Significantly high GCa risk in current WPT smokers (OR: 1.8; 95% CI: 1.3\u0026ndash;2.4)\u003c/p\u003e\n \u003cp\u003e\u0026bull; Current cigarette smoking was not a significant risk factor for GCa (OR: 1.1; 95% CI: 0.8\u0026ndash;1.4)\u003c/p\u003e\n \u003cp\u003e\u0026bull; No significant interaction between effects of WPT and cigarette smoking on GCa risk.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eLe, 2022\u003c/strong\u003e \u003csup\u003e\u003cstrong\u003e88\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eVietnam\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmoking / Waterpipe Smoking\u003c/p\u003e\n \u003cp\u003eCohort Study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 Northern Vietnam Provinces /\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;25619\u003c/p\u003e\n \u003cp\u003e2008\u0026ndash;2019\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eGCa\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026bull; Significantly higher GCa mortality among ever-smokers than never-smokers (aHR: 2.43; 95% CI: 1.35\u0026ndash;4.36)\u003c/p\u003e\n \u003cp\u003e\u0026bull; Exclusive WPT smokers showed the highest risk (HR: 3.22; 95% CI: 1.67\u0026ndash;6.21), followed by smokers of both WPT and cigarette (HR: 1.99; 95% CI: 0.89\u0026ndash;4.63), then exclusive cigarette smokers (HR: 1.90; 95% CI: 0.88\u0026ndash;4.07).\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eLee, 2016\u003c/strong\u003e \u003csup\u003e\u003cstrong\u003e89\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSouth Korea\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmoking\u003c/p\u003e\n \u003cp\u003eCase-Control Study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eKonkuk University Medical Center /\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;2961\u003c/p\u003e\n \u003cp\u003eJan. 2010-Jun. 2014\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eE (Asymptomatic)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026bull; Current smoking was an independent predisposing factor for AEE (OR 1.366; 95% CI: 1.068\u0026ndash;1.748)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eLevenstein, 2017\u003c/strong\u003e \u003csup\u003e\u003cstrong\u003e90\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDenmark\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmoking\u003c/p\u003e\n \u003cp\u003eCohort Study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCopenhagen County /\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;3365\u003c/p\u003e\n \u003cp\u003e1982\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003ePUD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026bull; Age-, gender-, and socioeconomic status-adjusted associations were significant for smoking (HR: 1.8; 95% CI: 1.1\u0026ndash;2.8).\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eLi, Guo, 2022\u003c/strong\u003e \u003csup\u003e\u003cstrong\u003e91\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eChina\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePM\u003csub\u003e2.5\u003c/sub\u003e\u003c/p\u003e\n \u003cp\u003eCross-Sectional\u003c/p\u003e\n \u003cp\u003ePopulation Study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e388 cancer registry institutes, Mainland China\u003c/p\u003e\n \u003cp\u003e2007\u0026ndash;2015\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eECa\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026bull; Significantly positive association between PM\u003csub\u003e2.5\u003c/sub\u003e and EC incidence.\u003c/p\u003e\n \u003cp\u003e\u0026bull; Lag effect of 4 years showed the greatest risk for males and females at 1.32% (95% CI: 1.20\u0026ndash;1.45%) and 2.70% (95% CI: 2.49\u0026ndash;2.92%), respectively.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eLi, Jing\u003c/strong\u003e,\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e2021\u003c/strong\u003e \u003csup\u003e\u003cstrong\u003e92\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eChina\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePM\u003csub\u003e2.5\u003c/sub\u003e\u003c/p\u003e\n \u003cp\u003eCross-Sectional\u003c/p\u003e\n \u003cp\u003ePopulation Study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e213 Prefectural Level Cities, Mainland China\u003c/p\u003e\n \u003cp\u003e2000\u0026ndash;2015\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eECa\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026bull; Stronger association between PM\u003csub\u003e2.5\u003c/sub\u003e and incidence observed in low urbanization groups, and association was stronger for females than males.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eLi, He, 2024\u003c/strong\u003e \u003csup\u003e\u003cstrong\u003e93\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eChina\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePM\u003csub\u003e2.5\u003c/sub\u003e\u003c/p\u003e\n \u003cp\u003eCross-Sectional Study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eJiangsu Province /\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;524019\u003c/p\u003e\n \u003cp\u003e2015\u0026ndash;2020\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eECa/GCa\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026bull; Long-term exposure to black carbon, organic carbon, nitrate, and ammonium was significantly associated with esophageal and stomach cancer.\u003c/p\u003e\n \u003cp\u003e\u0026bull; Sulfate exposure was significantly associated with stomach cancer.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eLin, Wu, 2020\u003c/strong\u003e \u003csup\u003e\u003cstrong\u003e94\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eChina\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmoking\u003c/p\u003e\n \u003cp\u003eCase-Control Study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eXianyou County, Fujian Province /\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;1244\u003c/p\u003e\n \u003cp\u003eMar. 2013-Jan. 2017\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eGCa\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026bull; Current cigarette smoking status was attributed to 83% increased risk of GCa (OR: 1.83, 95% CI: 1.19\u0026ndash;2.80)\u003c/p\u003e\n \u003cp\u003e\u0026bull; Smokers with longer duration of smoking (\u0026ge;\u0026thinsp;20 years) or started at later age (\u0026ge;\u0026thinsp;20 years) had nearly twofold increased risk of GCa vs. nonsmoker (OR: 1.97; 95% CI: 1.28\u0026ndash;3.04, OR: 2.02; 95% CI: 1.30\u0026ndash;3.14, respectively).\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eLin, Shih, 2022*\u003c/strong\u003e \u003csup\u003e\u003cstrong\u003e95\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTaiwan\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePM\u003csub\u003e2.5\u003c/sub\u003e\u003c/p\u003e\n \u003cp\u003eCross-Sectional\u003c/p\u003e\n \u003cp\u003ePopulation Study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEntire Population of Taiwan /\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;23.57 million\u003c/p\u003e\n \u003cp\u003e2010\u0026ndash;2017\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eECa\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026bull; Average number of deaths from esophagus cancer decreases 0.17 (95% CI: -0.22, -0.12) per 100,000 people with increasing average PM\u003csub\u003e2.5\u003c/sub\u003e concentration.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eMartinucci, 2018\u003c/strong\u003e \u003csup\u003e\u003cstrong\u003e96\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eItaly\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmoking\u003c/p\u003e\n \u003cp\u003eCross-Sectional Study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUniversity of Pisa /\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;3012\u003c/p\u003e\n \u003cp\u003eOct. 2016-May 2017\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eGERD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026bull; In the set of students with GERD, percentage of smokers was higher.\u003c/p\u003e\n \u003cp\u003e\u0026bull; In a multivariate analysis, smoking status showed an increased risk of GERD (OR: 1.6; 95% CI: 1.25\u0026ndash;2.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eMatsuzaki, 2015\u003c/strong\u003e \u003csup\u003e\u003cstrong\u003e97\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eJapan\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmoking\u003c/p\u003e\n \u003cp\u003eCase-Control Study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eKeio University Hospital /\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;2608\u003c/p\u003e\n \u003cp\u003eOct. 2012-Nov. 2013\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eE / BE\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026bull; Current smoking showed risks for RE and BE of OR: 1.79 (95% CI: 1.23\u0026ndash;2.60) and OR:1.37 (0.83\u0026ndash;2.26), respectively.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eMiftahussurur, 2018\u003c/strong\u003e \u003csup\u003e\u003cstrong\u003e98\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIndonesia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmoking\u003c/p\u003e\n \u003cp\u003eCase-Control Study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSurabaya /\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;104\u003c/p\u003e\n \u003cp\u003eOct. 2014-Nov. 2015\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eGERD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026bull; Smokers had a significantly higher risk of GERD compared to non-smokers (OR: 3.60; 95% CI: 1.298\u0026ndash;9.955)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eMinami, 2018\u003c/strong\u003e \u003csup\u003e\u003cstrong\u003e99\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eJapan\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmoking\u003c/p\u003e\n \u003cp\u003eCohort Study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMiyagi Cancer Center Hospital /\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;1576\u003c/p\u003e\n \u003cp\u003eJan. 1997-Dec. 2010\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eGCa\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026bull; Current smokers had increased risk of stomach cancer death in a multivariate adjusted model (HR: 1.25; 95% CI: 0.92\u0026ndash;1.69).\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eMlombe, 2015\u003c/strong\u003e \u003csup\u003e\u003cstrong\u003e100\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMalawi\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmoking\u003c/p\u003e\n \u003cp\u003eCase-Control Study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 tertiary teaching hospitals /\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;276\u003c/p\u003e\n \u003cp\u003eJan. 2011-Feb. 2013\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eECa\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026bull; In unadjusted analysis, odds of developing ESCC was 11.2 times higher among smokers than non-smokers, and in adjusted analysis it was 5.4 times higher.\u003c/p\u003e\n \u003cp\u003e\u0026bull; OR: 11.2 (95% CI: 5.2\u0026ndash;24.0) and aOR: 5.4 (2.0-15.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eMoses, 2017\u003c/strong\u003e \u003csup\u003e\u003cstrong\u003e101\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMalawi\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmoking\u003c/p\u003e\n \u003cp\u003eCohort Study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eKamuzu Central Hospital, Lilongwe /\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;172\u003c/p\u003e\n \u003cp\u003eJun. 2009-Sept. 2012\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eECa\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026bull; Esophageal cancer was among the commonest cancers in the cohort (n\u0026thinsp;=\u0026thinsp;172; 34.5%).\u003c/p\u003e\n \u003cp\u003e\u0026bull; Patients with esophageal cancer were more likely to be smokers (OR: 2.02).\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eNavab, 2015\u003c/strong\u003e \u003csup\u003e\u003cstrong\u003e102\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmoking\u003c/p\u003e\n \u003cp\u003eCross-Sectional Study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTertiary care center, PA\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;158\u003c/p\u003e\n \u003cp\u003e1999\u0026ndash;2008\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eBE\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026bull; Correlation coefficients for current and prior tobacco use were 0.73 (95% CI: 0.50\u0026ndash;1.06) and 0.92 (0.64\u0026ndash;1.31), respectively.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eNguyen, 2022\u003c/strong\u003e \u003csup\u003e\u003cstrong\u003e103\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eVietnam\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmoking / Waterpipe Smoking\u003c/p\u003e\n \u003cp\u003eCase-Control Study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBach Mai Hospital /\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;226\u003c/p\u003e\n \u003cp\u003eJan. 2018-Dec. 2018\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eGCa\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026bull; Compared to never tobacco smokers, risk of GCa significantly increased among tobacco smokers (OR: 2.95; 95% CI: 1.26\u0026ndash;6.90, p\u0026thinsp;=\u0026thinsp;0.013)\u003c/p\u003e\n \u003cp\u003e\u0026bull; For types of tobacco, increased risk was observed in exclusively cigarette smokers (OR: 3.26; 95% CI: 1.24\u0026ndash;8.55, p\u0026thinsp;=\u0026thinsp;0.017) and WPT smokers (OR: 2.90; 95% CI: 1.05\u0026ndash;7.97, p\u0026thinsp;=\u0026thinsp;0.039).\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eOkamoto, 2023\u003c/strong\u003e \u003csup\u003e\u003cstrong\u003e104\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eJapan\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmoking\u003c/p\u003e\n \u003cp\u003eCross-Sectional Study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEbina Medical Center, Ebina /\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;965\u003c/p\u003e\n \u003cp\u003eJan. 2015-Jun. 2015\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eRE\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026bull; Compared to never smokers, former and current smokers showed increased risk of RE (OR: 1.5; 95% CI: 0.9\u0026ndash;2.4, p\u0026thinsp;=\u0026thinsp;0.08) and (OR: 2.4; 95% CI: 1.5\u0026ndash;3.9, p\u0026thinsp;=\u0026thinsp;0.01), respectively.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eOkello, 2016\u003c/strong\u003e \u003csup\u003e\u003cstrong\u003e105\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUganda\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmoking\u003c/p\u003e\n \u003cp\u003eCase-Control Study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMbarara Regional Referral Hospital /\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;209\u003c/p\u003e\n \u003cp\u003eJan. 2003-Dec. 2014\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eECa\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026bull; In multivariate analysis, smoking was not statistically associated with ESCC.\u003c/p\u003e\n \u003cp\u003e\u0026bull; According to univariate analysis, smoking was significantly associated with ESCC (OR: 2.93; 95% CI: 1.43\u0026ndash;5.71, p\u0026thinsp;=\u0026thinsp;0.003). On multivariate analysis OR was 1.38 (95% CI: 0.41\u0026ndash;4.67, p\u0026thinsp;=\u0026thinsp;0.600).\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003ePan, 2019\u003c/strong\u003e \u003csup\u003e\u003cstrong\u003e106\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eChina\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmoking\u003c/p\u003e\n \u003cp\u003eCross-Sectional Study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHuai\u0026rsquo;an, Jiangsu Province /\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;11518\u003c/p\u003e\n \u003cp\u003eJan. 2011-Dec. 2017\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eECa\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026bull; Excessive smoking was associated with an increased risk of esophageal precancerous lesions (EPL)\u003c/p\u003e\n \u003cp\u003e\u0026bull; Consuming\u0026thinsp;\u0026gt;\u0026thinsp;30 cigarettes/day was significantly associated with EPL (OR: 1.75; 95% CI: 1.09\u0026ndash;2.80).\u003c/p\u003e\n \u003cp\u003e\u0026bull; Having 40 or more pack-years of cumulative amount of smoking was also significantly associated with EPL (OR: 1.40; 95% CI; 1.03\u0026ndash;1.89).\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003ePark, Kim, Jung, 2022\u003c/strong\u003e \u003csup\u003e\u003cstrong\u003e107\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSouth Korea\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmoking\u003c/p\u003e\n \u003cp\u003eCohort Study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eKorea National Health Insurance Database / N\u0026thinsp;=\u0026thinsp;43380\u003c/p\u003e\n \u003cp\u003e2002\u0026ndash;2013\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003ePUD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026bull; Compared to the never-never group, all other groups had significantly adjusted HRs for gastroduodenal ulcer.\u003c/p\u003e\n \u003cp\u003e\u0026bull; HR for current-current smokers was 1.379 (95% CI: 1.256\u0026ndash;1.513).\u003c/p\u003e\n \u003cp\u003e\u0026bull; Heavy smokers had the highest risk, followed by moderate and light smokers.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003ePark, Kim, Oh, 2022\u003c/strong\u003e \u003csup\u003e\u003cstrong\u003e108\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSouth Korea\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmoking\u003c/p\u003e\n \u003cp\u003eCohort Study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eKorea National Health Insurance Database / N\u0026thinsp;=\u0026thinsp;97700\u003c/p\u003e\n \u003cp\u003e2003\u0026ndash;2014\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eGCa\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026bull; Compared to the never-never group, current smokers had higher HRs for gastric Ca.\u003c/p\u003e\n \u003cp\u003e\u0026bull; HR for current-current smokers was 1.589 (95% CI: 1.355\u0026ndash;1.864).\u003c/p\u003e\n \u003cp\u003e\u0026bull; Risk for gastric cancer was highest in heavy smokers, followed by moderate smokers.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eQuan, 2015\u003c/strong\u003e \u003csup\u003e\u003cstrong\u003e109\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCanada\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePM\u003csub\u003e2.5\u003c/sub\u003e, PM\u003csub\u003e10\u003c/sub\u003e\u003c/p\u003e\n \u003cp\u003eCase-Crossover Study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCalgary (Discovery) and Edmonton (Replication) / N\u0026thinsp;=\u0026thinsp;1374 and 1159\u003c/p\u003e\n \u003cp\u003e2004\u0026ndash;2010\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003ePUD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026bull; When air pollution exposures were assessed as 3-, 5-, and 7- day averages, pollutants were inversely associated with UGIB in the discovery cohort.\u003c/p\u003e\n \u003cp\u003e\u0026bull; 5-day averages of PM\u003csub\u003e2.5\u003c/sub\u003e and PM\u003csub\u003e10\u003c/sub\u003e had ORs of 0.75 (95% CI: 0.61\u0026ndash;0.90) and 0.87 (95% CI: 0.75-1.00), respectively.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eRafiq, 2020\u003c/strong\u003e \u003csup\u003e\u003cstrong\u003e110\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIndia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmoking / Second-Hand Smoking\u003c/p\u003e\n \u003cp\u003eCase-Control Study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eKashmir /\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;2367\u003c/p\u003e\n \u003cp\u003eSept. 2008-Jan. 2012\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eECa\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026bull; Among never-tobacco users, the association between ever exposure to SHS and ECa risk were (OR: 1.32; 95% CI: 0.43\u0026ndash;4.02)\u003c/p\u003e\n \u003cp\u003e\u0026bull; Non-smokers exposed to SHS had OR of 1.25 (95% CI: 0.66\u0026ndash;2.38), whereas active smokers not exposed to SHS had OR of 1.49 (95% CI: 1.08\u0026ndash;2.04).\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eRamos, 2018\u003c/strong\u003e \u003csup\u003e\u003cstrong\u003e111\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBrazil\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmoking\u003c/p\u003e\n \u003cp\u003eCase-Control Study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSao Paolo /\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;739\u003c/p\u003e\n \u003cp\u003e2001\u0026ndash;2007\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eGCa\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026bull; Former and current smokers had ORs of 2.25 (95% CI: 1.53\u0026ndash;3.31) and 2.67 (95% CI: 1.72\u0026ndash;4.13), respectively.\u003c/p\u003e\n \u003cp\u003e\u0026bull; Smoking habit was associated with increased risk in all quartiles of consumption analyzed.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eRao, 2022\u003c/strong\u003e \u003csup\u003e\u003cstrong\u003e112\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eChina\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePM\u003csub\u003e2.5\u003c/sub\u003e\u003c/p\u003e\n \u003cp\u003eCross-Sectional Study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFujian Province /\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;5479\u003c/p\u003e\n \u003cp\u003eJan. 2016-Dec. 2016\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eECa\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026bull; Spatial distribution of hospitalization rate of ECa in 2016 was not consistent with that of concentration of PM\u003csub\u003e2.5\u003c/sub\u003e in same year.\u003c/p\u003e\n \u003cp\u003e\u0026bull; Concentration of PM\u003csub\u003e2.5\u003c/sub\u003e in 2003 and 2004 had strongest correlation with hospitalization rate of ECa in 2016, with Pearson correlation coefficient r value of -0.365.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eSadafi, 2024\u003c/strong\u003e \u003csup\u003e\u003cstrong\u003e113\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIran\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmoking\u003c/p\u003e\n \u003cp\u003eCross-Sectional Study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRavansar /\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;9631\u003c/p\u003e\n \u003cp\u003e2014\u0026ndash;2023\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eGERD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026bull; The odds of GERD among current smokers was 23% higher than non-smokers (OR: 1.23; 95% CI: 1.02\u0026ndash;1.55)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eSchmidt, 2020\u003c/strong\u003e \u003csup\u003e\u003cstrong\u003e114\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGermany\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmoking\u003c/p\u003e\n \u003cp\u003eCase-Control Study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSouthern Germany and Augsburg /\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;587 and 1976\u003c/p\u003e\n \u003cp\u003e2013\u0026ndash;2017\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eBE\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026bull; BE cases were statistically significantly more likely to smoke (32.3% vs 46.1% nonsmokers).\u003c/p\u003e\n \u003cp\u003e\u0026bull; Male patients with BE were significantly more likely to smoke (28.2% vs 38.3% non-smokers)\u003c/p\u003e\n \u003cp\u003e\u0026bull; 67.7% of BE cases were ever-smokers.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eSeo, 2020\u003c/strong\u003e \u003csup\u003e\u003cstrong\u003e115\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSouth Korea\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePM\u003csub\u003e2.5\u003c/sub\u003e, PM\u003csub\u003e10\u003c/sub\u003e\u003c/p\u003e\n \u003cp\u003eCross-Sectional Study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eKorea National Health Insurance Database / N\u0026thinsp;=\u0026thinsp;200000\u003c/p\u003e\n \u003cp\u003e2002\u0026ndash;2017\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eGERD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026bull; The final model of the study significantly predicted GERD-related medical utilization.\u003c/p\u003e\n \u003cp\u003e\u0026bull; In particular, PM\u003csub\u003e2.5\u003c/sub\u003e and CO were identified as risk factors for GERD.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eSewram, 2016\u003c/strong\u003e \u003csup\u003e\u003cstrong\u003e116\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSouth Africa\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmoking\u003c/p\u003e\n \u003cp\u003eCase-Control Study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 major public referral hospitals, East Cape Province / N\u0026thinsp;=\u0026thinsp;1858\u003c/p\u003e\n \u003cp\u003eNov. 2001-Feb. 2003\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eECa\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026bull; For males, ever smokers had 4-fold increased odds compared to never smokers (OR: 4.11; 95% CI: 2.55\u0026ndash;6.65)\u003c/p\u003e\n \u003cp\u003e\u0026bull; For females, ever smokers had 3.5-fold increase odd compared to non-smokers (OR: 3.45; 95% CI: 2.47\u0026ndash;4.82).\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eSimba, 2023\u003c/strong\u003e \u003csup\u003e\u003cstrong\u003e117\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eKenya, Tanzania, Malawi\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmoking\u003c/p\u003e\n \u003cp\u003eCase-Control Study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEldoret, Kenya; Moshi, Tanzania; Blantyre, Malawi / N\u0026thinsp;=\u0026thinsp;623, 1131, 870\u003c/p\u003e\n \u003cp\u003eAug. 2013-May 2020\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eECa\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026bull; Ever-tobacco use was associated with increased ESCC risk in all countries: Tanzania (OR: 3.09; 95% CI: 1.83\u0026ndash;5.23), Malawi (OR: 2.45; 95% CI: 1.80\u0026ndash;3.33), and lesser in Kenya (OR: 1.37; 95% CI: 0.94-2.00). Combined OR: 2.15 (95% CI: 1.72\u0026ndash;2.68)\u003c/p\u003e\n \u003cp\u003e\u0026bull; ESCC risk increased in with tobacco intensity and smoking duration.\u003c/p\u003e\n \u003cp\u003e\u0026bull; In all three countries, smoking tobacco showed increased risk of ESCC (OR: 2.28; 95% CI: 1.80\u0026ndash;2.89).\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eSong, 2024\u003c/strong\u003e \u003csup\u003e\u003cstrong\u003e118\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSouth Korea\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmoking\u003c/p\u003e\n \u003cp\u003eCross-Sectional Study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSeoul National University Bundang Hospital / N\u0026thinsp;=\u0026thinsp;14598\u003c/p\u003e\n \u003cp\u003eMay 2003-Feb. 2020\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eGCa\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026bull; In the univariate analysis smoking was significantly associated with single GCa and SGMC in all patients (OR: 0.971; 95% CI: 0.694\u0026ndash;1.359) and in EGCa and AGCa patients (OR: 1.200; 95% CI: 0.899\u0026ndash;1.602 and OR: 0.468; 95% CI: 0.231\u0026ndash;0.949, respectively)\u003c/p\u003e\n \u003cp\u003e\u0026bull; Multivariate analysis, smoking was significantly associated with single GCa and SGMC in AGCa patients.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eSpreafico, 2017\u003c/strong\u003e \u003csup\u003e\u003cstrong\u003e119\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUS / Canada\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmoking\u003c/p\u003e\n \u003cp\u003eCohort Study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBoston, MA and Toronto, Ontario /\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;564 (235; 329)\u003c/p\u003e\n \u003cp\u003e1999\u0026ndash;2004 \u0026amp; 2006\u0026ndash;2011\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eECa\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026bull; Smoking conferred worse overall survival in the combined Boston-Toronto Cohort with aHR of 1.22 (95% CI: 1.15\u0026ndash;1.43) for each 20 pack-year increase.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eSun, 2023\u003c/strong\u003e \u003csup\u003e\u003cstrong\u003e120\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eChina\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmoking / PM\u003csub\u003e2.5\u003c/sub\u003e\u003c/p\u003e\n \u003cp\u003eCohort Study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eChina Kadoorie Biobank /\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;510125\u003c/p\u003e\n \u003cp\u003e2005\u0026ndash;2017\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eECa\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026bull; A linear concentration-response relationship between long-term PM\u003csub\u003e2.5\u003c/sub\u003e exposure and ECa.\u003c/p\u003e\n \u003cp\u003e\u0026bull; Each 10-\u0026micro;g/m\u003csup\u003e3\u003c/sup\u003e increase in PM\u003csub\u003e2.5\u003c/sub\u003e, the HR for ECa was 1.16 (95% CI:1.04\u0026ndash;1.30)\u003c/p\u003e\n \u003cp\u003e\u0026bull; Using lowest group of PM\u003csub\u003e2.5\u003c/sub\u003e exposure as reference, HRs for other quartile groups, from low to high, were 1.09 (95% CI: 0.86\u0026ndash;1.37), 1.28 (95% CI: 0.98\u0026ndash;1.66), and 1.32 (95% CI: 1.01\u0026ndash;1.72).\u003c/p\u003e\n \u003cp\u003e\u0026bull; Subgroup analyses showed ever smoking had an HR of 1.18 (95% CI: 1.04\u0026ndash;1.35).\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eThrift, 2022\u003c/strong\u003e \u003csup\u003e\u003cstrong\u003e121\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmoking\u003c/p\u003e\n \u003cp\u003eCase-Control Study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHouston, TX /\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;1962\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eGCa (IM)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026bull; Compared to never smokers, current smokers had 2-fold increased risk for gastric intestinal metaplasia (OR: 2.05; 95% CI: 1.47\u0026ndash;2.85).\u003c/p\u003e\n \u003cp\u003e\u0026bull; Among ever smokers, increasing duration and total dose were significantly associated with increased risk (p\u0026thinsp;=\u0026thinsp;0.004 and 0.01, respectively).\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eTsai, 2019\u003c/strong\u003e \u003csup\u003e\u003cstrong\u003e122\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTaiwan\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePM\u003csub\u003e2.5\u003c/sub\u003e, PM\u003csub\u003e10\u003c/sub\u003e\u003c/p\u003e\n \u003cp\u003eCase-Crossover Study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTaipei /\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;23205\u003c/p\u003e\n \u003cp\u003e2009\u0026ndash;2013\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003ePUD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026bull; Increases in both PM\u003csub\u003e2.5\u003c/sub\u003e (OR: 1.14; 95% CI: 1.09\u0026ndash;1.18) and PM\u003csub\u003e10\u003c/sub\u003e (OR: 1.05; 95% CI: 1.01\u0026ndash;1.08) were significantly associated with increased risk of hospital admissions on warm days.\u003c/p\u003e\n \u003cp\u003e\u0026bull; On cool days, only increases in PM\u003csub\u003e10\u003c/sub\u003e were found to be significantly associated with increased risk of hospital admission (OR: 1.04; 95% CI: 1.02\u0026ndash;1.07).\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eWang, Leena, 2016\u003c/strong\u003e \u003csup\u003e\u003cstrong\u003e123\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIndia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmoking\u003c/p\u003e\n \u003cp\u003eCross-Sectional Study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTrivandrum District /\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;1072\u003c/p\u003e\n \u003cp\u003e2010\u0026ndash;2011\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eGERD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026bull; No association between cigarette smoking and risk of GERD.\u003c/p\u003e\n \u003cp\u003e\u0026bull; For the association of ever-smokers and risk of GERD, a mutually-adjusted analysis yielded OR of 0.7 (95% CI: 0.4\u0026ndash;1.2).\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eWang, Katki, 2021\u003c/strong\u003e \u003csup\u003e\u003cstrong\u003e124\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmoking\u003c/p\u003e\n \u003cp\u003eCohort Study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNIH-AARP Cohort /\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;490605\u003c/p\u003e\n \u003cp\u003e1995\u0026ndash;2011\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eECa/GCa\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026bull; For esophageal cancers, current smoking yielded HRs of 5.75 (95% CI: 3.90\u0026ndash;8.49) for ESCC and 3.16 (95% CI: 2.54\u0026ndash;3.92) for EADC.\u003c/p\u003e\n \u003cp\u003e\u0026bull; For gastric cancers, current smoking yielded HRs of 3.16 (95% CI: 2.42\u0026ndash;4.13) for GADC and 1.61 (95% CI: 1.27\u0026ndash;2.05) for GNCA.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eWei, 2021\u003c/strong\u003e \u003csup\u003e\u003cstrong\u003e125\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eChina\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmoking\u003c/p\u003e\n \u003cp\u003eCase-Control Study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFeicheng, Shandong /\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;464\u003c/p\u003e\n \u003cp\u003eJul. 2013-Apr. 2014\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eECa\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026bull; Ever smoking was associated with 3.11-fold increase in ESCC risk (OR: 3.11; 95% CI: 1.63\u0026ndash;6.05)\u003c/p\u003e\n \u003cp\u003e\u0026bull; For each cigarette-years increase in smoking index, ESCC risk increased by 56% (OR: 1.56; 95% CI: 1.18\u0026ndash;2.13).\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eWong, 2016\u003c/strong\u003e \u003csup\u003e\u003cstrong\u003e126\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eChina\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmoking / PM\u003csub\u003e2.5\u003c/sub\u003e\u003c/p\u003e\n \u003cp\u003eCross-Sectional Study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHong Kong /\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;66820\u003c/p\u003e\n \u003cp\u003eJul. 1998-Dec. 2001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003ePUD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026bull; Adjusted HR for PUD hospitalization per 10 \u0026micro;g/m\u003csup\u003e3\u003c/sup\u003e of PM\u003csub\u003e2.5\u003c/sub\u003e was 1.18 (95% CI: 1.02\u0026ndash;1.36).\u003c/p\u003e\n \u003cp\u003e\u0026bull; Associations with PM\u003csub\u003e2.5\u003c/sub\u003e were significant for gastric ulcers (HR: 1.29; 95% CI: 1.09\u0026ndash;1.53) but not for duodenal ulcers (HR: 0.98; 95% CI: 0.78\u0026ndash;1.22)\u003c/p\u003e\n \u003cp\u003e\u0026bull; For other variables, current smokers were to have significantly increased risk for hospitalization of PUD (HR: 1.59; 95% CI: 1.37\u0026ndash;1.84).\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eWu, 2021\u003c/strong\u003e \u003csup\u003e\u003cstrong\u003e127\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eChina\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePM\u003csub\u003e2.5\u003c/sub\u003e / PM\u003csub\u003e10\u003c/sub\u003e\u003c/p\u003e\n \u003cp\u003eEcological Study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYinzhou District, Ningbo City, Zhejiang Province / N\u0026thinsp;=\u0026thinsp;204257\u003c/p\u003e\n \u003cp\u003eJan. 2017-Dec. 2019\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003ePUD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026bull; Cumulative risk ratios for PM\u003csub\u003e2.5\u003c/sub\u003e and PM\u003csub\u003e10\u003c/sub\u003e showed nearly linear adverse effect and gently grew to maximums of 2.40 (95% CI: 1.36\u0026ndash;4.24) and 1.65 (95% CI: 0.98\u0026ndash;2.76), respectively.\u003c/p\u003e\n \u003cp\u003e\u0026bull; Significant associations for both men and women were only observed for PM\u003csub\u003e2.5\u003c/sub\u003e.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eYang, Lin, 2020\u003c/strong\u003e \u003csup\u003e\u003cstrong\u003e128\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eChina\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmoking\u003c/p\u003e\n \u003cp\u003eCase-Control Study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFujian Province /\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;423\u003c/p\u003e\n \u003cp\u003eJan. 2010-Dec. 2016\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eECa\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026bull; Tobacco smoking was related to ESCC risk, but no significant difference in magnitude of its association with respect to macroscopic type of cancer.\u003c/p\u003e\n \u003cp\u003e\u0026bull; Tobacco smoking showed increased risk for ulcerative type ESCC (OR: 2.24; 95% CI: 1.20\u0026ndash;4.19) and medullary type ESCC (OR: 2.56; 95% CI: 1.29\u0026ndash;5.06).\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eYang, Chen, 2017\u003c/strong\u003e \u003csup\u003e\u003cstrong\u003e129\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eChina\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmoking\u003c/p\u003e\n \u003cp\u003eCase-Control Study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTaixing /\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;3314\u003c/p\u003e\n \u003cp\u003eOct. 2010-Sept. 2013\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eECa\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026bull; In a fully adjusted analysis, current smokers had OR of 1.12 (0.88\u0026ndash;1.44) but not significant.\u003c/p\u003e\n \u003cp\u003e\u0026bull; Male heavy smokers (i.e., smoked more than 20 cigarettes/day or 40 pack-years or started smoking early) showed a moderately increased risk for ESCC.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eYates, 2014\u003c/strong\u003e \u003csup\u003e\u003cstrong\u003e130\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUK\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmoking\u003c/p\u003e\n \u003cp\u003eCohort Study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEPIC-Norfolk Cohort\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;24068\u003c/p\u003e\n \u003cp\u003e1993\u0026ndash;1997\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eBE/ECa\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026bull; Hazard ratios for current and former smokers for BE were 1.57 (95% CI: 0.83\u0026ndash;2.96) and 1.38 (95% CI: 0.88\u0026ndash;2.16), respectively.\u003c/p\u003e\n \u003cp\u003e\u0026bull; Hazard ratios for current and formers smokers for EAC were 1.82 (95% CI: 0.81\u0026ndash;4.09) and 1.27 (95% CI: 0.71\u0026ndash;2.27), respectively.\u003c/p\u003e\n \u003cp\u003e\u0026bull; Current and former smoking were not significantly associated with BE and EAC.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eYu, 2021\u003c/strong\u003e \u003csup\u003e\u003cstrong\u003e131\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eChina\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePM\u003csub\u003e2.5\u003c/sub\u003e\u003c/p\u003e\n \u003cp\u003eCross-Sectional Study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eZhejiang Province /\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;647,092\u003c/p\u003e\n \u003cp\u003eJan. 2014-Dec. 2018\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003ePUD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026bull; A potential dose-response relationship was observed between quartile concentrations of PM\u003csub\u003e2.5\u003c/sub\u003e 1 month before gastroscopy and detection of PUD. Subjects in the highest quartile of PM\u003csub\u003e2.5\u003c/sub\u003e exposure displayed significantly higher risk (OR: 1.178; 95% CI: 1.118\u0026ndash;1.242).\u003c/p\u003e\n \u003cp\u003e\u0026bull; The overall estimated OR for the detection of PUDs associated with a 10 \u0026micro;g/m\u003csup\u003e3\u003c/sup\u003e increase in PM\u003csub\u003e2.5\u003c/sub\u003e was 1.050 (95% CI: 1.038\u0026ndash;1.063)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eZacharakis, 2023\u003c/strong\u003e \u003csup\u003e\u003cstrong\u003e132\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSaudi Arabia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmoking\u003c/p\u003e\n \u003cp\u003eCohort Study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAl-Kharj, Riyadh /\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;1080\u003c/p\u003e\n \u003cp\u003eJan. 2017-May 2023\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eGCa\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026bull; Current and former smoking yielded ORs of 4.00 (95% CI: 2.05\u0026ndash;7.81) and 0.79 (95%. CI: 0.28\u0026ndash;2.24), respectively.\u003c/p\u003e\n \u003cp\u003e\u0026bull; Only current smoking was a significant risk factor for GCa (P\u0026thinsp;=\u0026thinsp;0.002)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eZhao, 2017\u003c/strong\u003e \u003csup\u003e\u003cstrong\u003e133\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eChina\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmoking\u003c/p\u003e\n \u003cp\u003eCase-Control Study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4 counties Jiangsu Province /\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;18093\u003c/p\u003e\n \u003cp\u003eJan. 2003-Dec. 2010\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eECa/GCa\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026bull; Tobacco smoking was associated positively with both esophageal (aOR: 1.68; 95% CI: 1.50\u0026ndash;1.87) and stomach cancer (aOR: 1.61; 95% CI: 1.43\u0026ndash;1.81).\u003c/p\u003e\n \u003cp\u003e\u0026bull; There was a significant does-response relationship between pack-years of smoking and risks of esophageal (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and stomach cancer (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e"},{"header":"RESULTS","content":"\u003cp\u003e \u003cb\u003eLiterature Search.\u003c/b\u003e A total of 764 studies were identified from PubMed and reference-list screening, Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. After removal of 222 duplicates, 542 articles were screened. Following application of inclusion criteria, 216 articles were excluded and 326 articles were assessed for eligibility based on exclusion criteria. Application of exclusion criteria involved removal of 141 non-original research articles, 85 translational studies, 27 case reports/series, and 9 pediatric studies for a total of 262 articles. N\u0026thinsp;=\u0026thinsp;64 original research articles were considered eligible and included in this review. Data from screening and extraction are available, \u003cb\u003eSupplemental Tables\u0026nbsp;1\u0026ndash;6.\u003c/b\u003e\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eRisk of bias using NOS was assessed in cohort (N\u0026thinsp;=\u0026thinsp;20), case-control (N\u0026thinsp;=\u0026thinsp;23), and cross-sectional studies (N\u0026thinsp;=\u0026thinsp;18), \u003cb\u003eSupplemental Table\u0026nbsp;7.\u003c/b\u003e Two studies that were case-crossover studies and one study that was an ecological study were unable to be assessed for risk of bias as the NOS and our adaptations did not cover for these types of studies. Scores obtained from the NOS were adapted as in previously published studies to reflect the quality of each paper.\u003csup\u003e69\u003c/sup\u003e Cutoffs for each risk of bias assessment depending on article type can be found within the footnote of \u003cb\u003eSupplemental Table\u0026nbsp;7.\u003c/b\u003e Among cohort studies, N\u0026thinsp;=\u0026thinsp;15 articles were of good quality, N\u0026thinsp;=\u0026thinsp;1 of fair quality, and N\u0026thinsp;=\u0026thinsp;4 of poor quality. Among case-control studies, N\u0026thinsp;=\u0026thinsp;15 were of good quality, N\u0026thinsp;=\u0026thinsp;5 of fair quality, and N\u0026thinsp;=\u0026thinsp;3 of poor quality. Among cross-sectional studies, N\u0026thinsp;=\u0026thinsp;14 were of good quality, N\u0026thinsp;=\u0026thinsp;2 of satisfactory quality, and N\u0026thinsp;=\u0026thinsp;2 of unsatisfactory quality.\u003c/p\u003e \u003cp\u003e \u003cb\u003eStudy Characteristics.\u003c/b\u003e The populations of patients with esophageal or gastric disease included those afflicted with esophagitis (n\u0026thinsp;=\u0026thinsp;8), BE (n\u0026thinsp;=\u0026thinsp;8), ECa (n\u0026thinsp;=\u0026thinsp;24), GERD (n\u0026thinsp;=\u0026thinsp;11), PUD Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Study design per Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Guidelines. PRISMA is an evidence-based minimum set of items for reporting in systematic reviews and meta-analyses.\u003csup\u003e66,67\u003c/sup\u003e\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;9), and GCa (n\u0026thinsp;=\u0026thinsp;16). Studies that focused on any other outcomes did not meet exclusion/inclusion criteria. The exposures that were investigated in particular were smoking, waterpipe smoking, and PM\u003csub\u003e2.5\u003c/sub\u003e/PM\u003csub\u003e10\u003c/sub\u003e exposure. While there were no studies that focused on marijuana smoking or vaping/e-cigarettes that met our inclusion/exclusion criteria we know from the literature that use of cannabinoids and vaping are linked to the development of gastrointestinal disorders.\u003csup\u003e134\u003c/sup\u003e One study investigated the role of exposure to second-hand smoke, in addition to direct cigarette smoke exposure.\u003csup\u003e110\u003c/sup\u003e Most studies produced an odds ratio (OR), risk ratio (RR), correlation coefficient (CC), or hazard ratio (HR) to measure each of the risks associated with their respective exposures for a particular outcome, of which are summarized in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e (see raw data in \u003cb\u003eSupplemental Table\u0026nbsp;8A-E\u003c/b\u003e). Among those studies, some reported using adjusted models in their analyses. Additionally, other studies focused on the percent presentation of risk factors;\u003csup\u003e72,86\u003c/sup\u003e risk by measuring the increase in incidence of the respective disease;\u003csup\u003e91\u0026ndash;93,114\u003c/sup\u003e the differences in mortality with respect to magnitude of exposure\u003csup\u003e95\u003c/sup\u003e, and utilized a novel predictive model to identify risk factors.\u003csup\u003e115\u003c/sup\u003e Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cb\u003eEsophagitis.\u003c/b\u003e Current tobacco use was identified as a significant risk factor for reflux esophagitis (RE).\u003csup\u003e73,77,97,104\u003c/sup\u003e When studying gender-specific differences between smoking and risk of RE, Kim, Jung, et al found that smoking led to greater risks of RE among women compared to men.\u003csup\u003e84\u003c/sup\u003e Associations between smoking and eosinophilic esophagitis (EE) were also investigated. Some studies found that EE were significantly less likely to have ever smoked cigarettes compared to non-EE controls, but smoking was not significantly associated with increased risk of EE.\u003csup\u003e74,86\u003c/sup\u003e Lee, et al, however, identified smoking as a significant risk factor for asymptomatic EE (AEE).\u003csup\u003e89\u003c/sup\u003e\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eBarrett\u0026rsquo;s Esophagus.\u003c/b\u003e Smoking was identified as a risk factor for BE.\u003csup\u003e73,97\u003c/sup\u003e Schmidt, et al found that BE cases were significantly more likely to smoke.\u003csup\u003e114\u003c/sup\u003e Navab, et al found positive correlation between current and prior tobacco use and BE.\u003csup\u003e102\u003c/sup\u003e Etemadi, et al found associations between smoking and BE that were independent of intensity, age at initiation, and GERD, but dependent on duration and years since cessation.\u003csup\u003e76\u003c/sup\u003e Other studies, however, produced conflicting results: some studies found that current and former smoking were not significantly associated with BE.\u003csup\u003e75,130\u003c/sup\u003e\u003c/p\u003e \u003cp\u003e \u003cb\u003eGastroesophageal Reflux Disease.\u003c/b\u003e Multiple studies identified smoking as a risk factor for GERD.\u003csup\u003e75,78,96,98,113\u003c/sup\u003e Kim, Jang, et al interestingly found that former smoking was significantly associated with risk of GERD, while current smoking was not significantly associated.\u003csup\u003e83\u003c/sup\u003e When investigating gender-specific differences on the effects of smoking on the risk of GERD, Kim, Jung, et al found that smoking increased risks in both men and women.\u003csup\u003e84\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eOne study investigated the effects of waterpipe smoking in addition to traditional cigarette smoking on the risk of GERD. Etemadi, et al found that waterpipe smoking was most strongly associated with \u0026ldquo;severe and frequent\u0026rdquo; reflux, and prevalence of the disease was associated with waterpipe use and duration. In addition, they found that cigarette smoking was a significant risk factor of any form of reflux among men.\u003csup\u003e76\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eConversely, some studies noted no significant association between GERD and smoking. Almadi, et al observed a higher prevalence of GERD among smokers than non-smokers, but found no significant difference.\u003csup\u003e70\u003c/sup\u003e Wang, Leena, et al also did not find any association between cigarette smoking and risk of GERD.\u003csup\u003e123\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eOne study, Seo, et al, developed a prediction model that was significantly able to predict GERD-related medical utilization in the South Korean population and identified PM\u003csub\u003e2.5\u003c/sub\u003e as a risk factor for GERD.\u003csup\u003e115\u003c/sup\u003e\u003c/p\u003e \u003cp\u003e \u003cb\u003ePeptic Ulcer Disease.\u003c/b\u003e Chuang, et al identified current tobacco use as a significant risk factor for PUD and that higher cumulative amounts of tobacco use were at higher risk for PUD.\u003csup\u003e73\u003c/sup\u003e Further, Begovic, et al found that more than half of ulcer patients enrolled into their study were smokers, and this difference was significant when compared to the those who were non-smokers.\u003csup\u003e72\u003c/sup\u003e Levenstein, et al observed that age-, gender-, and socioeconomic status-adjusted associations were significant for smoking.\u003csup\u003e90\u003c/sup\u003e\u003c/p\u003e \u003cp\u003ePark, Kim, Jung, et al investigated the role of changes in smoking status in risk of gastroduodenal ulcer. They observed that changes in smoking status from never smoker, quitter, and current smoker, to current smoker in particular had relatively higher HRs than other groups. When comparing smoking amount levels, they found that smokers who smoked\u0026thinsp;\u0026gt;\u0026thinsp;20 pack-years had significantly higher risk than lighter smokers.\u003csup\u003e107\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eOther studies had investigated the role of PM exposure in risk of PUD. Tsai, et al found that increases in both PM\u003csub\u003e2.5\u003c/sub\u003e and PM\u003csub\u003e10\u003c/sub\u003e were significantly associated with increased risk of PUD hospitalizations on warm days, but only PM\u003csub\u003e10\u003c/sub\u003e was significantly associated on cold days.\u003csup\u003e122\u003c/sup\u003e Similarly, Wong, et al found that PUD hospitalization was associated with 10 ug/m\u003csup\u003e3\u003c/sup\u003e increases in PM\u003csub\u003e2.5\u003c/sub\u003e. When investigating different types of ulcers, they found that associations with PM\u003csub\u003e2.5\u003c/sub\u003e were significant for gastric ulcers, but not for duodenal ulcers.\u003csup\u003e126\u003c/sup\u003e Wu, et al observed that cumulative RRs for PM\u003csub\u003e2.5\u003c/sub\u003e and PM\u003csub\u003e10\u003c/sub\u003e showed nearly linear adverse effects.\u003csup\u003e127\u003c/sup\u003e When looking at gender-adjusted differences, significant associations for men and women were only observed for PM\u003csub\u003e2.5\u003c/sub\u003e.\u003c/p\u003e \u003cp\u003eQuan, et al found that when air pollution exposures were assessed over 3-, 5-, and 7-day averages, pollutants were inversely associated with upper gastrointestinal bleeding (UGIB).\u003csup\u003e109\u003c/sup\u003e Yu, et al observed a potential dose-response relationship between quartile concentrations of PM\u003csub\u003e2.5\u003c/sub\u003e one month prior to detection of PUD. Subjects in the highest quartile of PM\u003csub\u003e2.5\u003c/sub\u003e exposure displayed significantly higher risk and the detection of PUD was associated with a 10 ug/m\u003csup\u003e3\u003c/sup\u003e in PM\u003csub\u003e2.5\u003c/sub\u003e.\u003csup\u003e131\u003c/sup\u003e\u003c/p\u003e \u003cp\u003e \u003cb\u003eEsophageal Cancer.\u003c/b\u003e Many studies found associations between smoking and ECa.\u003csup\u003e101,116,133\u003c/sup\u003e Other studies focused on esophageal squamous cell carcinoma and also identified smoking as a risk factor and this risk increased with tobacco intensity and smoking duration, but no significant difference with respect to macroscopic type of cancer, as smoking showed similarly increased risks for both ulcerative type and medullary type eosinophilic squamous cell carcinoma (ESCC).\u003csup\u003e81,85,100,117,125,128\u003c/sup\u003e Jayalekshmi, et al observed higher risks of ESCC for current bidi and cigarette smokers.\u003csup\u003e80\u003c/sup\u003e Conversely, some studies observed non-significant relationship between inhalational exposures and ECa.\u003csup\u003e73,105,129\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eSome studies looked at how smoking affected survival for those afflicted with ECa. Spreafico, et al found that smoking conferred worse overall survival in the combined Boston-Toronto Cohort for each 20 pack-year increase.\u003csup\u003e119\u003c/sup\u003e Other observed how current and former smoking contributed to decreased survival with respect to subtype, specifically ESCC and esophageal adenocarcinoma (EADC).\u003csup\u003e124,130\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eOne study in particular, Rafiq, et al evaluated both smoking and second-hand smoke as a risk factor for ECa, with increased risks associated with either exposure.\u003csup\u003e110\u003c/sup\u003e Another study, Pan, et al focused on associations between smoking and esophageal precancerous lesions (EPL) and found that consuming more than 30 cigarettes/day or having 40 or more pack-years of cumulative smoking was significantly associated with EPL.\u003csup\u003e106\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eOther studies investigated the relationship between PM\u003csub\u003e2.5\u003c/sub\u003e exposure and ECa. Li, Guo, et al observed a significantly positive association between PM\u003csub\u003e2.5\u003c/sub\u003e and ECa incidence. When investigating the corresponding lag effects on ECa incidence, they found that a lag effect of 4 years showed the greatest risk for males and females.\u003csup\u003e91\u003c/sup\u003e Li, Jing, et al examined the modifying effects of urbanization and socioeconomic factors and found a stronger association between PM\u003csub\u003e2.5\u003c/sub\u003e and incidence for low urbanization groups, and this association was stronger for females than males.\u003csup\u003e92\u003c/sup\u003e Li, He, et al identified long-term exposure to black carbon, organic carbon, nitrate, and ammonium to be significantly associated with ECa.\u003csup\u003e93\u003c/sup\u003e Rao, et al found that although spatial distributions of hospitalization rate of ECa in 2016 were not consistent with that of PM\u003csub\u003e2.5\u003c/sub\u003e concentration in the same year, concentrations of PM\u003csub\u003e2.5\u003c/sub\u003e in 2003 and 2004 had the strongest correlations with hospitalization rate in 2016.\u003csup\u003e112\u003c/sup\u003e Sun, et al observed a linear concentration-response relationship between long-term PM\u003csub\u003e2.5\u003c/sub\u003e and ECa.\u003csup\u003e120\u003c/sup\u003e Conversely, Lin, Shih, et al observed that the average number of deaths due to ECa decreases with increasing average PM\u003csub\u003e2.5\u003c/sub\u003e concentration.\u003csup\u003e95\u003c/sup\u003e\u003c/p\u003e \u003cp\u003e \u003cb\u003eGastric Cancer.\u003c/b\u003e As with the previous outcomes, most studies identified smoking as a risk factor for GCa.\u003csup\u003e71,111,132,133\u003c/sup\u003e Current cigarette smoking status was found to be attributed to increased risk of GCa and this risk increased among those with longer durations of smoking or later starting ages of smoking.\u003csup\u003e94\u003c/sup\u003e Current smoking was also found to have increased risk of stomach cancer death.\u003csup\u003e99\u003c/sup\u003e When assessing changes in smoking status, one study found that those who changed to their current status to \u0026ldquo;smoking\u0026rdquo; showed increased risk of GCa and this risk was the highest in heavier smokers.\u003csup\u003e108\u003c/sup\u003e One study found that smoking was only significantly associated with single GCa and synchronous multiple gastric cancer (SGMCa) in advanced gastric cancer (AGCa) patients.\u003csup\u003e118\u003c/sup\u003e Current smoking also showed increased risk for gastric adenocarcinoma (GAC) and gastric non-cardia adenocarcinoma (GNCA).\u003csup\u003e124\u003c/sup\u003e Interestingly, Jayalekshmi, et al found that bidi smoking was significantly associated with GCa risk, but cigarette smoking was not. This risk increased with the number of bidis smoked daily and with duration of bidi smoking.\u003csup\u003e79\u003c/sup\u003e Conversely, Chuang, et al found that tobacco use was a non-significant risk factor for GCa.\u003csup\u003e73\u003c/sup\u003e Other studies found that current smoking increased risks of intestinal metaplasia for both men and women. Further, this risk increased with increasing duration and total dose.\u003csup\u003e82,121\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eSome studies investigated the role of waterpipe smoking in GCa risk. Several studies in Vietnam showed that water pipe smoking was positively associated with GCa risk, but there was no significant interaction between the effects of water pipes and cigarette smoking on GCa risk.\u003csup\u003e87,88,103\u003c/sup\u003e Li, He, et al found that long-term exposure to black carbon, organic carbon, nitrate, ammonium, and sulfate was significantly associated with stomach cancer.\u003csup\u003e93\u003c/sup\u003e\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eIn this systematic review, we investigated the associations between environmental exposures and diseases of the upper gastrointestinal tract. Through a comprehensive review of the available literature, we identified complex relationships between environmental exposures and upper gastrointestinal diseases. Most of the studies showed that exposures including particulate matter, smoking, and waterpipe were significantly associated with higher risk of aerodigestive diseases.\u003c/p\u003e \u003cp\u003eParticulate matter (PM) exposure is a global cause of significant pulmonary morbidity and mortality.\u003csup\u003e6\u0026ndash;46\u003c/sup\u003e Our review supports existing evidence suggesting that exposure to PM may also increase the risk of diseases affecting the upper gastrointestinal tract. Studies included in this review demonstrated links between PM exposure and an increased risk of ECa and PUD, although the underlying mechanisms remain to be fully explained. These findings highlight the importance of considering environmental factors, such as air pollution, in the context of upper gastrointestinal health. PM consists of various harmful compounds which can trigger inflammatory responses, oxidative stress and DNA damage that contribute to the development of cancer and ulceration. Moreover, studies showed that PM may disrupt the gut microbiota, leading to increased risk of gastrointestinal inflammation and cancers.\u003csup\u003e135\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eCigarette smoking has been recognized as a major risk factor for various cancers, including those of the gastrointestinal tract. Consistent with previous research, our review highlights the detrimental effects of smoking on the upper gastrointestinal tract, with a notable association observed between smoking and an elevated risk of Barrett\u0026rsquo;s esophagus, GCa, ECa and PUD. The carcinogenic effect of smoking is attributable to mutations in critical genes caused by tobacco metabolites and chemicals. Smoking is also associated with progression, aggressiveness, and reduced survival rates of existing gastrointestinal cancers. Smoking may be associated with exacerbation of GERD symptoms due to reducing esophageal sphincter tone and increasing gastric acid production.\u003csup\u003e136\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eWaterpipe smoking has increased worldwide due to a perception that it is less harmful than cigarette smoking. However, waterpipe smoke contains tobacco and several toxicants that may increase the risk of developing aerodigestive disease, as identified in our review. Numerous carcinogens have been identified in waterpipe smoke including polycyclic aromatic hydrocarbons (PAHs), volatile aldehydes, and heavy metals, which can cause DNA damage and develop cancer over time.\u003csup\u003e137\u003c/sup\u003e Moreover, emerging evidence suggests that vaping and marijuana use may also impact gastrointestinal health, although further investigation is warranted to better understand the nature of these associations.\u003c/p\u003e \u003cp\u003eGastrointestinal symptoms associated with vaping can occur in more than half of exposed patients.\u003csup\u003e138,139\u003c/sup\u003e The gastrointestinal symptoms are thought to be directly related to the inhalation of nicotine; users of novel nicotine delivery products (vapers) usually take in higher doses of nicotine than tobacco smokers.\u003csup\u003e140\u003c/sup\u003e Nausea, vomiting, diarrhea and abdominal pain are also signs of with E-cigarette or Vaping Product Use\u0026ndash;Associated Lung Injury (EVALI), as indicated in several case reports.\u003csup\u003e141\u003c/sup\u003e In a survey of UK vapers (that met our exclusion criteria), the incidence of the new symptom vomiting amongst \u0026ldquo;current vapers\u0026rdquo; was 13.0% and 21% for nausea. Current vapers using cannabinoid-based substances reported nausea significantly more frequently than other groups. Respondents reporting vomiting/nausea were given the diagnosis of gastritis or gastroenteritis. The incidence of nausea and vomiting was not increased in exclusive vapers compared to concurrent smokers and vapers.\u003csup\u003e142\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eIn tobacco smokers, due to the burning process, nicotine can be transformed into nitrosamines via nitrosation, and many of these nitrosamines, such as nicotine-derived nitrosamine ketone (NNK) and N-nitrosonornicotine (NNN), are potent carcinogens linked to esophageal and stomach cancer.\u003csup\u003e143,144\u003c/sup\u003e Novel delivery devices such as e-cigarettes produce 5% as much nitrosamines compared to standard burning tobacco products, leading to an assumption that e-cigarettes are safer than cigarettes and could be used as cessation aids. However, translational \u003cem\u003ein vitro\u003c/em\u003e and murine studies showed that nicotine from e-cigarette induced carcinogenic DNA-adducts and inhibited DNA repair just like nicotine-derived nitrosamine ketone (NNK). Because it often takes over two decades for tobacco smokers to develop cancer, mice were exposed to e-cigarette vapors for one year and had their organs examined. While cancers were detected in the lungs of the mice due to e-cigarette exposure, cell hyperplasia also occurred in the bladder epithelium, raising the possibility that although e-cigarette exposure is inhalational, it can cause systemic cancers.\u003c/p\u003e \u003cp\u003eFurthermore, the nicotinic acetylcholine receptor (nAChR), a genetic variant of which is consistently linked to lung cancer in large genetic studies, might mediate carcinogenesis through directly binding nicotine (and nitrosamines) in airway epithelium. This mechanism could provide direct carcinogenesis of nicotine and nicotine-metabolites to all cells that express the nAChR, particularly in carriers of the variants that are associated with tobacco smoking and cancer.\u003csup\u003e145\u0026ndash;148\u003c/sup\u003e Following the idea that inhaled nicotine could produce carcinogenic molecules in human users, an untargeted metabolomics analysis of urine demonstrated a trend of increased carcinogen biomarkers in the samples of a relatively small cohort of vapers (n\u0026thinsp;=\u0026thinsp;34 vs. n\u0026thinsp;=\u0026thinsp;45 non-users).\u003csup\u003e149\u003c/sup\u003e\u003c/p\u003e"},{"header":"Limitations","content":"\u003cp\u003eWhile this systematic review provides valuable insights into the associations between environmental exposures and upper gastrointestinal diseases, the included studies vary in design, methodology, and population characteristics, which may introduce heterogeneity and bias. Some studies used adjusted models when calculating ORs or HRs (aOR; aHR). It is possible that these adjustments are complex and vary widely across these studies, further contributing to heterogeneity. Additionally, the majority of studies are observational in nature limiting causal inference and necessitating further research, including prospective cohort studies and mechanistic investigations. This study only relied on the PubMed database for the identification of potentially eligible studies. Our risk of bias assessment (NOS) was able to evaluate the majority but not all studies assessed in this review.\u003c/p\u003e \u003cp\u003eOther limitations revolved around how we defined environmental exposure and aerodigestive disease as a whole. Our study defined environmental exposures as air pollution in the form of particulate matter, cigarette/tobacco smoke, marijuana smoke, vape/e-cigarette aerosols. Due to this, it was not possible to completely cover the entire scope of environmental exposures that afflict society. In addition, our definition of aerodigestive disease focused on diseases of the upper gastrointestinal tract, which comprised of esophagitis, Barrett\u0026rsquo;s esophagus, GERD, PUD, and esophageal/gastric cancer based on the articles we found. It is very likely that there are other aerodigestive diseases that interact strongly with environmental exposures that were not covered by this paper. Due to these definitions and our inclusion/exclusion criteria, we also found no eligible articles that investigated the interactions of marijuana smoke and vape/e-cigarette aerosols with aerodigestive disease.\u003c/p\u003e"},{"header":"Future Research","content":"\u003cp\u003eCurrently, there are no human studies available to clearly define the cancer-inducing potential of non-burning nicotine delivery products such as e-cigarettes. However, this could be due to the very extensive lag time between carcinogen exposure and clinical cancer diagnosis in humans. Future studies could expand our definitions to account for interactions not present within this review, such as those of marijuana smoking, vaping, and those of the lower intestinal tract. Additionally, future studies could assess the contribution of specific occupational exposures to aerodigestive health, as this study only focused on exposures commonly experienced by the general population. Such additional exposures include asbestos, synthetic fiber dust, chrysotile dust, nephrite, and potentially harmful elements (PHEs) which are all commonly present in mining or textile industries and in developing societies in general. Such investigations could yield valuable insights for those whose occupation or geographic location puts them at risk for such diseases, as aerodigestive disease is often not recognized for those working/living under such conditions. In addition, this could identify how specific exposures incite disease in various cohorts.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe implications of these findings are significant from both a public health and clinical perspective. Efforts to reduce exposure to environmental pollutants, such as particular matter, could potentially mitigate the burden of upper gastrointestinal diseases in affected populations. Similarly, targeted interventions aimed at reducing smoking behavior and promoting smoking cessation may help reduce the incidence of BE and malignancy. Furthermore, continued research into the potential health effects of emerging trends, such as vaping and marijuana use, is crucial for informing preventive strategies and improving patient outcomes.\u003c/p\u003e\n\u003cp\u003eThis review provides support for the connection between environmental exposures and digestive health, which is especially important considering that those who have been exposed to environmental/occupational inhalants are generally not covered for their digestive health. We hope that this review will promote further recognition of treatment of digestive disease with inhalational exposure.\u003c/p\u003e\n\u003cp\u003eIn conclusion, this systematic review contributes to our understanding of the interplay between exposure to inhalational exposures and diseases of the upper gastrointestinal tract. By synthesizing existing evidence and identifying knowledge gaps, this study highlights the need for approaches to address environmental risk factors and promote gastrointestinal health.\u003cstrong\u003e\u003cbr\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e"},{"header":"Abbreviation","content":"\u003cp\u003e\u003cstrong\u003eAEE\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/strong\u003eAsymptomatic Erosive Esophagitis\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAGCa\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/strong\u003eAdvanced Gastric Cancer\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAHR\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/strong\u003eAirway Hyperreactivity\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eaOR\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/strong\u003eAdjusted Odds Ratio\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eBE\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/strong\u003eBarrett\u0026rsquo;s Esophagus\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCa\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/strong\u003eCancer\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCC\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/strong\u003eCorrelation Coefficient\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCI\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/strong\u003eConfidence Interval\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eE\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/strong\u003eEsophagitis\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEAC\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/strong\u003eEsophageal Adenocarcinoma\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eECa\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/strong\u003eEsophageal Cancer\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEE\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/strong\u003eEosinophilic Esophagitis\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEPL\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/strong\u003eEsophageal Precancerous Lesions\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eESCC\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/strong\u003eEsophageal Squamous Cell Carcinoma\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eGAC\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/strong\u003eGastric Adenocarcinoma\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eGERD\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/strong\u003eGastroesophageal Reflux Disease\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eGCa\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/strong\u003eGastric Cancer\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eGNCA\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/strong\u003eGastric Non-Cardia Adenocarcinoma\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHR\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/strong\u003eHazard Ratio\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eNOS\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/strong\u003eNew-Castle Ottawa Scale\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOAD\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/strong\u003eObstructive Airway Disease\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOR\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/strong\u003eOdds Ratio\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePAH\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/strong\u003ePolycyclic Aromatic Hydrocarbons\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePEO\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/strong\u003ePopulation, Exposure, Outcome\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePHE\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/strong\u003ePotentially Harmful Elements\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePM \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/strong\u003eParticulate Matter\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePUD\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/strong\u003ePeptic Ulcer Disease\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRE\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/strong\u003eReflux Esophagitis\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRR\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/strong\u003eRisk Ratio\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSGMCa\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/strong\u003eSynchronous Multiple Gastric Cancer\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSHS\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/strong\u003eSecond-Hand Smoke\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eUGIB\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/strong\u003eUpper Gastrointestinal Bleeding\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eWHO\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/strong\u003eWorld Health Organization\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eWPT\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/strong\u003eWaterpipe Tobacco\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eWTC \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/strong\u003eWorld Trade Center\u003cstrong\u003e\u003cbr\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003e\u003cstrong\u003eData Availability\u003c/strong\u003e\u0026nbsp;\u003c/h2\u003e\n\u003cp\u003eAll data generated or analyzed during this study are included in this published article and its supplementary information files.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eFunding Sources:\u003c/strong\u003e This work was supported by CDC/NIOSH U01 -OH012069; -OH011855; -OH011300 (AN); NIH NCATS: \u0026nbsp;UL1TR001445; KL2TR001446 (SK); Stony Wold-Herbert Fund (SK); NIH NIEHS: 1L70HL170444-01 (SK); NIH NIEHS R01ES032808 (ML).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe would like to acknowledge the World Trade Center Health Program and World Trade Center-Exposed 9/11 rescue workers.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eAuthor Information\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors and Affiliations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDepartment of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, New York University Grossman School of Medicine (NYUGSoM); New York (NY), NY, USA\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDaniel Hyun Kim, Sanjiti Podury, Aida Fallah Zadeh, Sophia Kwon, Anna Nolan\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Department of Medicine, Division of Environmental Medicine, NYUGSoM, NY, NY, USA\u003c/p\u003e\n\u003cp\u003eGabrielle Grunig, Anna Nolan\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Department of Population Health, Division of Biostatistics; NYUGSoM, NY, NY, USA\u003c/p\u003e\n\u003cp\u003eMengling Liu\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eContributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDHK, SP, and AN conceived and planned the systematic review. DHK and SP carried out the literature search. DHK, SP, and AN performed screening of articles. DHK carried out data extraction and analysis. DHK took the lead in writing the manuscript. All authors provided critical feedback and helped shape the research, analysis and manuscripts.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eCorresponding Author\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCorrespondence to Anna Nolan\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e\u003c/strong\u003e\u003cstrong\u003eEthics Declaration\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eExposure Science, Available online: https://www.niehs.nih.gov/health/topics/science/exposure. 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T., Hu, Y., Chen, L. C., Park, S. H., Chan, H. W., Xu, J., Wu, X. R., Wang, H., Yang, R., Galdane, K., Jackson, K., Chu, A. \u0026amp; Halzack, E. DNA damage, DNA repair and carcinogenicity: Tobacco smoke versus electronic cigarette aerosol. \u003cem\u003eMutat Res Rev Mutat Res\u003c/em\u003e \u003cstrong\u003e2022, \u003c/strong\u003e \u003cem\u003e789\u003c/em\u003e, 108409, doi:10.1016/j.mrrev.2021.108409.\u003c/li\u003e\n\u003cli\u003eHsiao, Y. C., Matulewicz, R. S., Sherman, S. E., Jaspers, I., Weitzman, M. L., Gordon, T., Liu, C. W., Yang, Y., Lu, K. \u0026amp; Bjurlin, M. A. Untargeted Metabolomics to Characterize the Urinary Chemical Landscape of E-Cigarette Users. \u003cem\u003eChem Res Toxicol\u003c/em\u003e \u003cstrong\u003e2023, \u003c/strong\u003e \u003cem\u003e36\u003c/em\u003e, 630-642, doi:10.1021/acs.chemrestox.2c00346.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Systematic Review, Environmental Exposure, Smoking, Particulate Matter, Aerodigestive Disease","lastPublishedDoi":"10.21203/rs.3.rs-4650430/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4650430/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eEnvironmental exposure-associated disease is an active area of study, especially in the context of increasing global air pollution and use of inhalants. Our group is dedicated to the study of exposure-related inflammation and downstream health effects. While many studies have focused on the impact of inhalants on respiratory sequelae, there is growing evidence of the involvement of other systems including autoimmune, endocrine, and gastrointestinal.\u003c/p\u003e \u003cp\u003eThis systematic review aims to provide a recent update that will underscore the associations between inhalation exposures and upper gastrointestinal disease in the contexts of our evolving environmental exposures. Keywords focused on inhalational exposures and gastrointestinal disease. Primary search identified n\u0026thinsp;=\u0026thinsp;764 studies, of which n\u0026thinsp;=\u0026thinsp;64 met eligibility criteria. In particular, there was support for existing evidence that PM increases the risk of upper gastrointestinal diseases. Smoking was also confirmed to be major risk factor. Interestingly, studies in this review have also identified waterpipe use as a significant risk factor for gastroesophageal reflux and gastric cancer.\u003c/p\u003e \u003cp\u003eOur systematic review identified inhalational exposures as risk factors for aerodigestive disease, further supporting the association between environmental exposure and digestive disease. However, due to limitations on our review\u0026rsquo;s scope, further studies must be done to better understand this interaction.\u003c/p\u003e","manuscriptTitle":"Gastroesophageal Disease and Environmental Exposure: A Systematic Review","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-07-31 09:18:12","doi":"10.21203/rs.3.rs-4650430/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-08-23T07:11:14+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-08-22T16:00:34+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-08-17T15:17:37+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-08-11T20:49:03+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"88084574575778288614318686888303358956","date":"2024-08-11T05:23:37+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"109307393095876627834512898592864046002","date":"2024-08-11T05:03:28+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"204783976535898033609630242858924157687","date":"2024-08-11T03:48:31+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-07-29T14:29:02+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-07-29T14:26:05+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-07-11T14:14:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-07-08T05:05:18+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2024-06-27T17:41:36+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"a7442032-01aa-4e33-98aa-73f9a2e821d8","owner":[],"postedDate":"July 31st, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-07-07T16:11:04+00:00","versionOfRecord":{"articleIdentity":"rs-4650430","link":"https://doi.org/10.1038/s41598-025-06620-7","journal":{"identity":"scientific-reports","isVorOnly":false,"title":"Scientific Reports"},"publishedOn":"2025-07-02 15:57:50","publishedOnDateReadable":"July 2nd, 2025"},"versionCreatedAt":"2024-07-31 09:18:12","video":"","vorDoi":"10.1038/s41598-025-06620-7","vorDoiUrl":"https://doi.org/10.1038/s41598-025-06620-7","workflowStages":[]},"version":"v1","identity":"rs-4650430","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4650430","identity":"rs-4650430","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}