Domestic burning of incense and mosquito coils on the risk of nasopharyngeal carcinoma: Systematic review and meta-analysis

Domestic burning of incense and mosquito coils on the risk of nasopharyngeal carcinoma: Systematic review and meta-analysis | 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 Research Article Domestic burning of incense and mosquito coils on the risk of nasopharyngeal carcinoma: Systematic review and meta-analysis Jia-Xiu Xu, Lap Ah Tse, Ignatius Tak-sun Yu, Shao-Hua Xie This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4874108/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objectives To clarify the association between incense and mosquito coils burning and the risk of nasopharyngeal carcinoma (NPC), we performed this systematic review of epidemiological studies. Methods A search of studies published through October 2022 in MEDLINE and EMBASE databases was performed, supplemented by searches of reference lists, recent reviews, and Chinese databases. The quality of the included studies was assessed with special reference to exposure assessment. Random-effect meta-analysis estimated the pooled odds ratios (OR) and 95% confidence interval (CI) whenever applicable. Results One cohort and 12 case-control studies were identified. The cohort study found no association between incense burning and NPC risk. In meta-analysis of six case-control studies with reasonable quality, the pooled OR for incense burning during adulthood was 1.61 (95% CI 1.43–1.81). Five studies assessed association between exposures to incense smoke during childhood and NPC risk, and the pooled OR was 1.22 (95% CI 0.76–1.96) associated with incense burning at birth and was 1.37 (95% CI 1.10–1.71) for exposure at the age of 10 years. The pooled OR for mosquito coils burning during adulthood was 1.30 (95% CI 1.04–1.62). None of the four previous case-control studies found an increased risk of NPC associated with mosquito coils burning during childhood. Conclusions Our findings suggest an increased NPC risk associated with incense burning and mosquito coils. More epidemiological studies with refined exposure assessment are still warranted. incense mosquito coils nasopharyngeal carcinoma systematic review meta-analysis risk factor Figures Figure 1 Figure 2 1. Introduction Nasopharyngeal carcinoma (NPC) is a malignancy which has fascinated generations of epidemiologists for its distinctive geographical and racial variations in incidence. NPC is rare in most parts of the world with age-adjusted incidence rates less than 1 per 100 000 persons per year irrespective of sex, but high incidence rates of NPC are noted in certain areas, including Southern China and Southeast Asia [ 1 – 5 ] . Although the etiology of NPC has not been completely understood, it has become increasingly clear that NPC is a multi-factorial disease resulting from the joint effects of virus infection, environmental exposures, and genetic susceptibility [ 1 , 6 ]. The unique spatial and ethnic clustering and a decrease in incidence since the 1970s-1980s in Chinese populations in Hong Kong, Taiwan, and Singapore[ 1 , 7 – 10 ] strongly suggest that some environmental exposures related to traditional lifestyles in these high-risk populations could have played a role in the development of NPC. Incense burning, a traditional daily practice in Chinese households, is a powerful producer of carcinogens such as polycyclic aromatic hydrocarbons (PAHs), benzene, and formaldehyde[ 11 , 12 ]. Incense burning has been reported to be the major contributor to PAHs in Hong Kong homes [ 13 ]. Toxicological studies have also shown mutagenic and genotoxic activities of incense smoke condensates in mammalian cells [ 14 , 15 ]. Burning of mosquito coils is a common practice at least several months per year in many households, especially in tropical and sub-tropical countries. Smokes from mosquito coils burning contain considerably high levels of suspected carcinogens including PAHs and formaldehyde [ 16 , 17 ]. Thus, domestic burning of incense and mosquito coils may be risk factor for respiratory tract carcinomas, including those in upper respiratory tract such as NPC. Previous epidemiological studies have examined the associations between domestic burning of incense and mosquito coils and the risk of NPC, though the results remain inconsistent[ 18 – 27 ]. To clarify such associations, we conducted this systematic review of available epidemiological evidence with a comprehensive literature search, quality assessment and a statistical synthesis of available evidence. Needs for future research in light of the methodological issues in previous studies are also discussed hereby. 2. Methods 2.1. Search strategy A comprehensive search of studies published through October 2022 in MEDLINE and Embase databases was performed through the interface provided by Ovid with no language restriction. Briefly, a combination of key words for the exposures (incense or mosquito coils) and the outcome (NPC) were used to identify relevant publications. The full electronic search strategy is presented in Supplemental Table 1. The reference lists of identified articles of and four comprehensive reviews on epidemiology of NPC[ 1 , 5 , 6 , 28 ] were also reviewed to identify additional studies. 2.2. Inclusion criteria Studies meeting the following criteria were included in this review: (1) case-control or cohort epidemiological studies published as original articles; (2) the studied outcome being NPC incidence rather than mortality; (3) the association of incense or mosquito coils burning with NPC risk being examined. In the case of multiple reports on the same population, only the most recent or informative ones would be included. We only included studies which contained the minimum information necessary to estimate the odds ratio (OR) or relative risk (RR) with the reference group of non-users of incense or mosquito coils and a corresponding measure of statistical uncertainty (confidence interval [CI], standard error, variance, chi square and degree of freedom, or P value, etc.) into meta-analysis. 2.3. Assessment of study quality The quality of the included studies was assessed in terms of the major sources of selection bias, information bias and confounding with the help of checklists for appraising studies on risk factors developed by Yu and Tse [ 29 – 31 ]. The essential information regarding selection retrieved from case-control studies mainly included type (whether incident/newly diagnosed) and histological confirmation of cases, source and definition of controls, and response rate; the risk of selection bias in cohort studies was mainly assessed in terms of representativeness of the cohort and the completeness and duration of the follow-up. Retrieved information regarding exposure assessment included that on the exposure period, frequency, duration, intensity and cumulative exposures. For cohort studies, risk of information bias for outcome was assessed on the method of ascertainment (independent blind assessment, record linkage, or self-reported) and whether the follow-up was long enough for NPC to occur. Comparability of cases and controls (risk of confounding) was assessed by examining what potential confounding factors have been considered and controlled for in statistical analyses. The Newcastle-Ottawa Scale (NOS) for assessing the quality of non-randomized studies in meta-analyses was also used to evaluate the quality of selected studies [ 32 ]. The NOS contains eight items which are categorized into three domains, including selection of participants, comparability between groups, and assessment of exposure (case-control studies) or outcome (cohort studies). The NOS allocates stars, raging zero to nine, for quality of non-randomized studies such that studies with higher quality are scored higher stars. 2.4. Meta analysis The software Review Manager 5.4 was used for meta-analysis. Random-effect models were used to obtain pooled estimates of effect size and their 95% Cis. Heterogeneity across studies was assessed based on chi square tests and the I 2 index statistic. Low level of heterogeneity was defined as I 2 ≤ 25%, accompanied by P > 0.10 in the chi square test. Publication bias was assessed by visual inspection of funnel plots. Sensitivity analysis was conducted by removing one study at a time to examine fluctuations of the pooled effect size. A two-sided P value less than 0.05 was considered statistically significant. 3. Results A total of 507 articles were identified in MEDLINE and Embase, and 14 additional studies were identified from reference lists of reviews and articles of interest. After a careful review of titles and abstracts, and full texts if needed, 508 articles were excluded for duplication (7), irrelevance (496), or not being cohort or case-control study (5). Finally, this systematic review included 13 individual studies, among which there were 12 case-control studies [ 18 – 25 , 27 , 33 – 35 ] and 1 cohort study[ 26 ]. The flow chart of study selection is illustrated in Supplemental Fig. 1. Three case-control studies were not included in further meta-analyses for associations between incense burning and NPC risk because two of them did not provide enough data to estimate effect size and uncertainty [ 23 , 24 ] and the other one reported estimates of effect size using participants in all the other exposure groups, instead of non-users of incense, as reference [ 34 ]. 3.1. Cohort study Only one previous cohort study investigated the effect of incense burning on the risk of NPC [ 26 ]. This cohort study included 61 320 Singapore Chinese aged 45–74 years who were recruited between 1993 and 1998 and followed up through 2005. The study quality of this study was reasonably good with NOS quality score of 8 given the methodological strengths, including representativeness of the original cohort (population-based including 85% of eligible individuals), complete follow-up (99.7%), comprehensive and prospective exposure assessment, objective assessment of outcome (91.3% histologically confirmed), and efforts to control for potential confounders (adjusting for age, gender, dialect group, education, body mass index, smoking, drinking, dietary items, and for women, parity). A total of 175 NPC cases were diagnosed during the follow-up; however, the follow-up period (12 years at most) might not be long enough for all potential NPC cases to occur. The association between incense burning and NPC risk were examined based on multiple exposure indicators and no statistically significant associations were found. The adjusted hazard ratios (HRs) for NPC were 0.7 (95% CI: 0.4–1.4) in former users and 0.8 (95% CI 0.5–1.3) for current uses of incense, using never users as the reference group. No exposure-response relations were observed. The HRs were 0.7 (95% CI: 0.3–1.5) for less than daily current use, 1.0 (95% CI: 0.6–1.7) for daily use for 40 years or less, and 1.0 (95% CI: 0.7–1.4) for daily use for over 40 years. 3.2. Case-control studies The 12 identified case-control studies were published between 1966 and 2021, among which 11 were conducted in Chinese population of different geographic areas, including Mainland China, Hong Kong, Taiwan, and Singapore, and the remaining one was conducted in Filipinos. The number of cases ranged 47 to 2533 across individual studies. Only four studies adjusted a set of various potential confounders in multivariate analyses. The majority of these studies obtained NOS quality scores ranging 5 to 8 except for the earliest study published in 1966 with a score of 2 (Supplementary Table 2). More detailed characteristics of the 12 case-control studies are summarized in Tables 1 and 2 . Table 1 Basic characteristics of identified case-control studies First author Year Region Ethnicity Sex (% male) Age (year) Period No. of Cases No. of Controls Sturton 1966 Hong Kong Chinese Cases: 62%; controls: 35% 70% of cases and 35% of controls were under 50 years Oct 1963 - Jun 1965 47 217 Lin 1973 Taiwan Chinese 73% Cases: 46.7 ± 11.5; controls: 46.2 ± 11.4 Dec 1969 - May 1971 343 1017 Geser 1978 Hong Kong Chinese 70% 15–65+; Median: cases 49.1, controls 51.1 Jan 1973 - Feb 1974 150 150 Shanmugaratnam 1978 Singapore Chinese Cases: 70%; controls: 64% Cases: 10–70+, median 47.4; controls: 0–70+, median 46.3 Mar 1966 - Aug 1968 379 1639 Yu 1986 Hong Kong Chinese 64% Under 35; cases: mean 29.2; controls: mean 28.6 Feb 1981 - 250 250 Yu 1988 Guangxi, China Chinese 70% Under 45; cases: mean 36.0; controls: mean 35.8 May 1984 - Nov 1986 128 174 Yu 1990 Guangzhou, China Chinese 68% Under 50 Mar 1983 - Aug 1985 306 306 West 1993 Philippine Filipino 73% 11–83, median 46 Duration of 24 months 104 208 Lee 1994 Singapore Chinese Cases: 73%; controls: 71% Cases: median 37.9; controls: median 38.5 Mar 1988 - Dec 1990 200 406 He 2015 Guangdong Chinese Cases: 73.12%; controls: 70.77༅ Cases: 46.11 ± 10.99; controls: 46.42 ± 11.74 Oct 2005 - Oct 2007 1845 2275 Chen 2021 Guangdong、Guangxi Chinese Cases: 73.4%; controls: 73.5༅ 20–74 2010–2014 2533 2597 Xie 2014 Hong Kong Chinese Cases: 71.9%; controls: 73.4༅ 20–75 Jun 2010-Dec 2012 352 410 Table 2 Characteristics related to validity of identified case-control studies Study Type of cases Histological confirmation Source of controls Response Matched factors Adjusted factors Sturton 1966 N/A N/A Hospital (cancer patients) N/A Stratified by age, and sex Lin 1973 Incident 95.90% Community Cases: 91.9%; controls: 85% Sex, age, and neighborhood Geser 1978 Incident N/A Hospital N/A Sex and age Shanmugaratnam 1978 N/A 100% Hospital N/A Age, sex and interviewer Yu 1986 Incident 98% Community (friend) Cases: 94.0%; controls: 99.2% Sex and age Salted fish intake during weaning and at age of10 year Yu 1988 Incident 100% Community Cases: 90.7%; controls: N/A Sex, age, and race Yu 1990 Incident 100% Community 100% Sex, age, and residence Dietary factors West 1993 Incident 100% Two series: hospital and community Cases: 100%; hospital controls: 100%; community controls: 77% Hospital controls: sex, age, and hospital ward type; community controls: sex, age and neighborhood Education, occupational. exposures, smoking, fresh fish and processed meat intake, and herbal medicine use Lee 1994 Incident N/A Hospital Cases: 88.6%; controls: 92.5% He 2015 N/A N/A Hospital Cases: 94.7%; controls༚95.5% Sex and age Age、sex、education、housing type、cigarette smoking pack-years、salted fish、preserved vegetables、tea、herbal tea、slowcooked soup and family history Chen 2021 Incident 100% Community Cases: 84%; controls༚83༅ Sex, age and geographic area distribution Age、sex、geographic area、education、occupation、first-degree family history、cigarette smoking、tea、oral hygiene and salt-preserved fish Xie 2014 Incident 100% Hospital Cases: 94.4%; controls༚93.8༅ Age, sex and residence Men: age, smoking, environmental tobacco smokes, education, housing type, family history of NPC, intake of dark green vegetables, fruits, vitamins and supplements, drinking herbal tea, occupational exposures, and cooking experience at home; Women: age, ETS, education, and family history N/A: not available Eleven of the 12 studies assessed exposures to incense or mosquito coils smokes during adulthood based on usual or recent practice (4 for incense burning only, 1 for mosquito coils burning only, and 6 for both). Three of the 12 studies, all by research group of Yu et al, also assessed exposures at the age of 10 years and at birth [ 18 – 20 ]. One recent study assessed exposures at the ages of 10, 18, and 30 years [ 27 ]. One study assessed exposures to incense smoke during childhood but did not further clarify the specific period [ 34 ]. Seven studies reported frequency data, but only one out of the twelve case-control studies considered other aspects of exposure, such as intensity and duration [ 21 ](Table 3 ). Table 3 Exposure assessment in the included studies Study Exposure periods Frequency Intensity Duration Cumulative exposure Incense burning Mosquito coils burning Cohort study Friborg 2008 at baseline not assessed yes yes yes yes Case-control studies Sturton 1966 adulthood not assessed no no no no Lin 1973 adulthood not assessed no no no no Geser 1978 adulthood not assessed no no no no Shanmugaratnam 1978 adulthood, childhood adulthood yes no no no Yu 1986 3 years ago, age 10, at birth 3 years ago, age 10, at birth no no no no Yu 1988 at birth, age 10 at birth, age 10 yes no no no Yu 1990 3 years ago, age 10, at birth 3 years ago, age 10, at birth yes no no no West 1993 not assessed adulthood yes no no no Lee 1994 adulthood not assessed no no no no He 2015 adulthood adulthood yes no no no Chen 2021 Ages of 10, 18 and 30, in recent 10 years Ages of 10, 18 and 30, in recent 10 years yes no no no Xie 2014 adulthood adulthood yes yes yes no 3.2.1. Incense burning during adulthood Ten previous case-control studies evaluated the associations between incense burning during adulthood and NPC risk. Among these, three studies simply reported the results as negative or not statistically significant [ 20 , 23 , 24 ], and one study reported estimates of RRs not using non-users of incense as reference [ 34 ]. The remaining 6 studies were included in meta-analysis, generating pooled OR of 1.61 (95% CI: 1.43, 1.81) in random-effect model (Fig. 1 a). The heterogeneity tests suggested low heterogeneity across studies ( P = 0.39, I 2 = 4%). After excluding the earliest study with low quality score, the pooled OR decreased slightly to 1.58 (95% CI: 1.41, 1.78). The funnel plot suggested possible publication bias as one study with the highest OR estimate had the largest standard error (Supplemental Fig. 2), but the pooled OR did not substantially changed in sensitivity analysis excluding this specific study (Supplemental Fig. 3). 3.2.2. Incense burning during childhood Five previous case-control studies, including three studies from the research group of Yu et al, examined the association between incense burning at early ages and NPC risk in Chinese populations of different areas. None of them found statistically significant associations. For exposure at birth, one of these three studies only reported the results as non-significant ( P = 0.14). The pooled OR for NPC risk associated with incense burning at birth combining two studies was 1.22 (95% CI 0.76–1.96) (Fig. 1 b). For exposure at the age of 10 years, two studies described the results as non-significant ( P = 0.34 and P = 0.23). The pooled OR for NPC associated with incense burning at the age of 10 years combining the other two studies was 1.37 (95% CI 1.10–1.71) (Fig. 1 c). 3.2.3. Mosquito coils burning during adulthood Six previous case-control studies reported associations between mosquito coils burning during adulthood and NPC risk. One of these studies only reported the results as negative ( P = 0.39), and thus, was not included in the subsequent meta-analysis. Meta-analysis of the remaining five studies generated a pooled OR of 1.30 (95% CI 1.04–1.62) in random-effects model, with substantial heterogeneity across studies ( P = 0.004, I 2 = 74%) (Fig. 2 ). The pooled OR did not substantially changed in sensitivity analysis removing one study at each time (Supplemental Fig. 4). 3.2.4. Mosquito coils burning during childhood The three case-control studies from the research group of Yu et al examined the associations between mosquito coils burning at early ages and NPC risk, and none of them reported statistically significant findings. Another recent study reported an OR of 0.84 (95% CI 0.75–0.95) for NPC risk associated with mosquito coils burning in summer at the age of 10 years [ 27 ]. 4. Discussion This updated systematic review of existing epidemiological studies investigated the associations of incense and mosquito coils burning with NPC risk. The results revealed increased risk of NPC associated with incense burning during both adulthood and childhood periods and mosquito coils burning during adulthood, but evidence regarding mosquito coils burning during childhood remains limited. The carcinogenic potentials of emissions from incense and mosquito coils burning have been intensively documented in previous literature of environmental chemistry and toxicology. Incense smoke is an important source of residential indoor PMs, including those less than 2.5µm in the diameter (PM 2.5 ) which pose the largest health risks in all types of PMs [ 11 , 36 – 40 ]. It has been reported that incense burning produced PM over 45 mg/g burned, which was dramatically high than that burned for cigarettes (10 mg/g) [ 41 ]. Incense burning also generates various types of VOCs, including benzene, PAHs, and formaldehyde which are confirmed or probable carcinogens to humans [ 42 – 50 ]. Burning of mosquito coils is also a powerful producer of carcinogenic agents, such as PAHs and formaldehyde [ 16 , 17 ]. The emission of PM 2.5 mass from burning one mosquito coil was as high as that from burning 75–137 cigarettes. Burning one mosquito coils would release the same amount of formaldehyde as that from burning 51 cigarettes [ 16 ]. Toxicological studies have shown that PM extracts from incense smoke is mutagenic in the Ames Salmonella test with TA98 and activation and the genotoxicity of certain incense smoke condensates in mammalian cells may be even higher than that of tobacco smoke condensates [ 11 , 14 , 15 ]. Given the fact that inhalation is the primary route of exposure to smokes from incense and mosquito coils burning, burning of incense and mosquito coils may be an important risk factor for malignancies in the respiratory tract including NPC. The pooled results of meta-analysis in the present study showed an increased risk of NPC associated with incense burning. However, the findings should be interpreted with caution given that publication bias was likely to be present. No associations between mosquito coils burning during childhood and the NPC risk were indicated in previous studies. It is possible to be explained by non-differential exposure misclassification regarding exposure in early life, which would have biased the results towards null, and the fact that burning mosquito coils is only an occasional practice in selective seasons, unlike incense burning which is often a long-term daily practice. Epidemiological studies on health effects of environmental pollutants need accurate exposure assessment. Inaccurate exposure assessment can cause exposure misclassification, which may result in biased results and/or loss of study power, in addition to a failure in documenting a clear exposure-response relationship. Because incense and mosquito coils burning was not the primary risk factor of interest in previous case-control studies, the exposure assessment methods concerning burning of incense and mosquito coils were quite crude, e.g. only dichotomized to ever/never-exposed categories or just frequencies of burning. Only one of previous case-control studies considered other important aspects of exposure [ 21 ]. In addition, these studies only used the usual (recent) burning practice for exposure assessment, though several studies also assessed exposures at early ages. Changes of behaviors over time or cumulative exposures were not considered. Even in the cohort study of reasonable study quality, the exposure assessment was based on incense burning practice at baseline only and did not adequately reflect lifetime exposure. Lack of accurate exposure assessment, particularly if non-differential, in previous studies may have diluted the observed associations between domestic incense and mosquito coils burning and NPC risk. Since NPC is a relatively rare disease, cohort study design seems not an efficient method of investigation on risk factors of NPC. The reasonably large cohort study among Singapore Chinese only observed 175 NPC cases during follow-up and might not have adequate statistical power. Thus, case-control studies, especially those in high-risk regions, may continue to be the major designs in investigating the etiology of NPC due to its feasibility and efficiency. The potential risk of selection bias in this systematic review needs to be discussed hereby. A comprehensive searching strategy has been adopted to identify all published studies reporting the associations of interest. Because only a limited number of studies were specifically designed to investigate the associations of incense burning with NPC risk and the majority of these studies were published in earlier periods, several included studies were not identified through electronic searching, suggesting that electronic databases may not be sufficient for identifying studies dating back to early days. Although the original authors were also contacted for detailed information when the published results were not sufficient for meta-analysis, no additional information was obtained mainly because the data records had been destroyed after the completion of their studies. Results of the meta-analyses were probably prone to publication bias because some estimates without statistical significance were not included in meta-analyses. The validity of results in meta-analyses can be affected by that in primary studies. Although 9 of included case-control studies reported considerably high response rates, the remaining 3 did not report response rates, posing a certain risk of selection bias. Three studies did not mention whether recruited cases were incident or prevalent. If incense or mosquito coils burning is associated with poor survival of NPC patients, recruiting prevalent cases might have resulted in underestimated effects of incense or mosquito coils burning because those with poor survival, who were more likely to burn incense or mosquito coils, might have been missed. Seven studies used hospital-based controls, among which one even used cancer patients as controls [ 22 ]. If control participants were diagnosed with diseases associated with incense or mosquito coils burning, the results might have been biased, for which the direction away from the true estimates depends on the specific diseases which control participants were diagnosed with. If incense or mosquito coils burning is associated with an increased risk of diseases which control participants had, the effects of incense or mosquito coils burning might have been underestimated. However, if control participants were affected by some specific diseases (e.g. asthma), they were likely to avoid exposures to smokes, which might have resulted in overestimated effects of incense or mosquito coils burning on NPC risk. Community-based controls were used in 6 of included studies. Two studies also used friend or neighborhood controls and it was possible to cause overmatching and make the estimates towards the null. In addition, even when community-based controls were used, the risk of misclassification of outcomes would be minor given that NPC is rare in the general population. Although the same methods of exposure assessment were used for cases and controls in previous studies, there remains certain risk of misclassification in previous case-control studies because of the retrospective nature of such designs. However, it was probable non-differential since incense burning and mosquito coils burning are not well-established risk factors for NPC. Hence, the resulting bias, if any, would have been towards the null. It is notable that limited efforts have been made to control for potential confounders in most of previous studies. Since incense burning is a traditional practice in some Asian populations, it is probably correlated with some other types of traditional lifestyle. Failure in controlling for potential confounding effects from other risk factors associated with traditional lifestyle may have compromised the validity of the results, leading to over- or under-estimated effects. Overall, results of meta-analyses in this systematic review were possibly subject to bias as a result of the inaccurate magnitude of association reported in the original studies that could have arisen from various sources of bias in those studies. 5. Conclusions In conclusion, although synthesized results of previous studies suggested an increased risk of NPC associated with incense burning and mosquito coils, existing evidence from epidemiological studies remains far from enough to accurately assess such associations. Needs are highlighted for refined exposure assessment methods, good efforts to control for confounders, and increased sample size for an adequate study power in future investigations. Declarations Funding Declaration Author Contribution Jia-Xiu Xu（First Author）:Conceptualization,Formal Analysis,Methodology,Software,Visualization,Writing-Original Draft.Lap Ah Tse:Methodology,Writing-Original Draft.Ignatius Tak-sun Yu:Methodology,Writing-Original Draft.Shao-Hua Xie(Corresponding Author):Conceptualization,Methodology,Project Administration,Supervision,Visualization,Writing-Original Draft,Writing-Review＆Editing. Data Availability Data is provided within the manuscript or supplementary information files References Chang ET, Adami H-O. The Enigmatic Epidemiology of Nasopharyngeal Carcinoma. Cancer Epidemiol Biomarkers Prev. 2006;15(10):1765–77. Busson P, Keryer C, Ooka T, Corbex M. EBV-associated nasopharyngeal carcinomas: from epidemiology to virus-targeting strategies. Trends Microbiol. 2004;12(8):356–60. Zhang Y, Rumgay H, Li M, Cao S, Chen W. 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Workshop 5–Sources of bias in cohort studies. Hong Kong Med J. 2012;18(2):137–8. Yu IT, Tse SL. Workshop 4–Sources of bias in case-referent studies. Hong Kong Med J. 2012;18(1):46–7. Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol. 2010;25(9):603–5. West S, Hildesheim A, Dosemeci M. Non-viral risk factors for nasopharyngeal carcinoma in the philippines: Results from a case‐control study. Int J Cancer. 1993;55(5):722–7. Shanmugaratnam K, Tye Cy Fau -, Goh EH, Goh Eh Fau -, Chia KB, Chia KB. Etiological factors in nasopharyngeal carcinoma: a hospital-based, retrospective, case-control, questionnaire study. IARC Sci Publ. 1978;20:199–212. Geser A, Charnay N, Fau - Day NE, Day Ne Fau - de-The G, de-The GF, Ho HC, Ho HC. Environmental factors in the etiology of nasopharyngeal carcinoma: report on a case-control study in Hong Kong. IARC Sci Publ 1978, 20(213–229). Jetter JJ, Guo Z, McBrian JA, Flynn MR. Characterization of emissions from burning incense. Sci Total Environ. 2002;295(1–3):51–67. Fang G-C, Chu C-C, Wu Y-S, Fu PP-C. Emission characters of particulate concentrations and dry deposition studies for incense burning at a Taiwanese temple. Toxicol Ind Health. 2002;18(4):183–90. Fang G-C, Chang C-N, Wu Y-S, Yang C-J, Chang S-C, Yang IL. Suspended particulate variations and mass size distributions of incense burning at Tzu Yun Yen temple in Taiwan, Taichung. Sci Total Environ. 2002;299(1–3):79–87. Fang G-C, Chang C-N, Chu C-C, Wu Y-S, Pi-Cheng Fu P, Chang S-C, Yang IL. Fine (PM 2.5), coarse (PM 2.5–10), and metallic elements of suspended particulates for incense burning at Tzu Yun Yen temple in central Taiwan. Chemosphere. 2003;51(9):983–91. Brauer M, Hirtle R, Lang B, Ott W. Assessment of indoor fine aerosol contributions from environmental tobacco smoke and cooking with a portable nephelometer. J Expo Sci Environ Epidemiol. 2000;10(2):136–44. Mannix RC, Nguyen KP, Tan EW, Ho EE, Phalen RF. Physical characterization of incense aerosols. Sci Total Environ. 1996;193(2):149–58. Yang T-T, Lin S-T, Lin T-S, Hong W-L. Characterization of polycyclic aromatic hydrocarbon emissions in the particulate phase from burning incenses with various atomic hydrogen/carbon ratios. Sci Total Environ 2012, 414(1879 – 1026 (Electronic)):335–42. Wang B, Lee S, Ho K, Kang Y. Characteristics of emissions of air pollutants from burning of incense in temples, Hong Kong. Sci Total Environ. 2007;377(1):52–60. Schoental R, GlBbard S. Carcinogens in Chinese Incense Smoke. Nature. 1967;216(5115):612–612. Manoukian A, Quivet E, Temime-Roussel B, Nicolas M, Maupetit F, Wortham H. Emission characteristics of air pollutants from incense and candle burning in indoor atmospheres. Environ Sci Pollut Res. 2013;20(7):4659–70. Lin T-C, Chang F-H, Hsieh J-H, Chao H-R, Chao M-R. Characteristics of polycyclic aromatic hydrocarbons and total suspended particulate in indoor and outdoor atmosphere of a Taiwanese temple. J Hazard Mater. 2002;95(1–2):1–12. Lin JM, Wang LH. Gaseous aliphatic aldehydes in Chinese incense smoke. Bull Environ Contam Toxicol. 1994;53(3):374–81. Lee RS, Lin JM. Gaseous Aliphatic Aldehydes in Smoke from Burning Raw Materials of Chinese Joss Sticks. Bull Environ Contam Toxicol. 1996;57(3):361–6. Ho SSH, Yu JZ. Concentrations of formaldehyde and other carbonyls in environments affected by incense burning. J Environ Monit. 2002;4(5):728–33. Guo Z, Jetter JJ, McBrian JA. Rates of Polycyclic Aromatic Hydrocarbon Emissions from Incense. Bull Environ Contam Toxicol. 2004;72(1):186–93. Additional Declarations No competing interests reported. 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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-4874108","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":339245696,"identity":"7a7c7e33-82a4-4b25-84fd-9b1bd9f371fe","order_by":0,"name":"Jia-Xiu Xu","email":"","orcid":"","institution":"Fujian Medical University","correspondingAuthor":false,"prefix":"","firstName":"Jia-Xiu","middleName":"","lastName":"Xu","suffix":""},{"id":339245697,"identity":"c8a36f82-2429-4980-b699-8036a9a93610","order_by":1,"name":"Lap Ah Tse","email":"","orcid":"","institution":"Chinese University of Hong Kong","correspondingAuthor":false,"prefix":"","firstName":"Lap","middleName":"Ah","lastName":"Tse","suffix":""},{"id":339245698,"identity":"fff84983-5543-4d5b-8d28-ec70b7ba8600","order_by":2,"name":"Ignatius Tak-sun Yu","email":"","orcid":"","institution":"Chinese University of Hong Kong","correspondingAuthor":false,"prefix":"","firstName":"Ignatius","middleName":"Tak-sun","lastName":"Yu","suffix":""},{"id":339245699,"identity":"9bbf1ca5-adcc-4da7-a24b-2945b6bcea75","order_by":3,"name":"Shao-Hua Xie","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAyklEQVRIiWNgGAWjYDACCQYGZjCDmYHxYYMBiVqYDUnUwsDAJtlAjA752c0PHxe22TEYHGc+VjmjgMGen5AWgzvHjI1ntiUzSDazpd3cYMCQOJOQVQYSCWbSvG3MDPzMPGY3HxgwJBgcIOSwGenfgFrqGdiY+b8VArXY2xPSwnAjB2TLYZAtbIxAhzFuIOiXGznFxjznjvMA/WIsOcNAInEGEQ7b+JinrFrO4Pzhhx97/tjY8zcQsgYKeKC0BJHqR8EoGAWjYBTgBQCk/TVX27f4UAAAAABJRU5ErkJggg==","orcid":"","institution":"Karolinska Institutet, Karolinska University Hospital","correspondingAuthor":true,"prefix":"","firstName":"Shao-Hua","middleName":"","lastName":"Xie","suffix":""}],"badges":[],"createdAt":"2024-08-07 10:52:09","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4874108/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4874108/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":66123459,"identity":"2c000ad7-9e94-4eb6-ad2d-662b33f44fc1","added_by":"auto","created_at":"2024-10-08 02:27:25","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":607768,"visible":true,"origin":"","legend":"\u003cp\u003eForest plots of pooled odds ratios for nasopharyngeal carcinoma associated with incense burning during adulthood (a), at birth (b) and at the age of 10 years (c) in previous case-control studies.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-4874108/v1/30a9069f3f202009b9a42a47.png"},{"id":66123458,"identity":"d900f975-c66a-479f-bd33-5d7b82daa4d3","added_by":"auto","created_at":"2024-10-08 02:27:25","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":886469,"visible":true,"origin":"","legend":"\u003cp\u003eForest plots of pooled odds ratios for nasopharyngeal carcinoma associated with mosquito coils burning during adulthood in previous case-control studies.\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-4874108/v1/02f75b9597105ce0e65b9027.png"},{"id":79614393,"identity":"deb0c883-6fca-4c0b-bc78-bc9a2c838c20","added_by":"auto","created_at":"2025-03-31 18:46:25","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2619659,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4874108/v1/fda1dabe-ec64-41d4-80d9-b54b9c62dcba.pdf"},{"id":66123460,"identity":"e57f751a-f70c-432e-8427-9336d09c5c2f","added_by":"auto","created_at":"2024-10-08 02:27:25","extension":"pdf","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":312034,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementalMaterials.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4874108/v1/02432360b93484a3eaeeb9bb.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Domestic burning of incense and mosquito coils on the risk of nasopharyngeal carcinoma: Systematic review and meta-analysis","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eNasopharyngeal carcinoma (NPC) is a malignancy which has fascinated generations of epidemiologists for its distinctive geographical and racial variations in incidence. NPC is rare in most parts of the world with age-adjusted incidence rates less than 1 per 100 000 persons per year irrespective of sex, but high incidence rates of NPC are noted in certain areas, including Southern China and Southeast Asia [\u003cspan additionalcitationids=\"CR2 CR3 CR4\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] .\u003c/p\u003e \u003cp\u003eAlthough the etiology of NPC has not been completely understood, it has become increasingly clear that NPC is a multi-factorial disease resulting from the joint effects of virus infection, environmental exposures, and genetic susceptibility [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. The unique spatial and ethnic clustering and a decrease in incidence since the 1970s-1980s in Chinese populations in Hong Kong, Taiwan, and Singapore[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan additionalcitationids=\"CR8 CR9\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] strongly suggest that some environmental exposures related to traditional lifestyles in these high-risk populations could have played a role in the development of NPC.\u003c/p\u003e \u003cp\u003eIncense burning, a traditional daily practice in Chinese households, is a powerful producer of carcinogens such as polycyclic aromatic hydrocarbons (PAHs), benzene, and formaldehyde[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Incense burning has been reported to be the major contributor to PAHs in Hong Kong homes [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Toxicological studies have also shown mutagenic and genotoxic activities of incense smoke condensates in mammalian cells [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Burning of mosquito coils is a common practice at least several months per year in many households, especially in tropical and sub-tropical countries. Smokes from mosquito coils burning contain considerably high levels of suspected carcinogens including PAHs and formaldehyde [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Thus, domestic burning of incense and mosquito coils may be risk factor for respiratory tract carcinomas, including those in upper respiratory tract such as NPC.\u003c/p\u003e \u003cp\u003ePrevious epidemiological studies have examined the associations between domestic burning of incense and mosquito coils and the risk of NPC, though the results remain inconsistent[\u003cspan additionalcitationids=\"CR19 CR20 CR21 CR22 CR23 CR24 CR25 CR26\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. To clarify such associations, we conducted this systematic review of available epidemiological evidence with a comprehensive literature search, quality assessment and a statistical synthesis of available evidence. Needs for future research in light of the methodological issues in previous studies are also discussed hereby.\u003c/p\u003e"},{"header":"2. Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1. Search strategy\u003c/h2\u003e \u003cp\u003eA comprehensive search of studies published through October 2022 in MEDLINE and Embase databases was performed through the interface provided by Ovid with no language restriction. Briefly, a combination of key words for the exposures (incense or mosquito coils) and the outcome (NPC) were used to identify relevant publications. The full electronic search strategy is presented in Supplemental Table\u0026nbsp;1. The reference lists of identified articles of and four comprehensive reviews on epidemiology of NPC[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e] were also reviewed to identify additional studies.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2. Inclusion criteria\u003c/h2\u003e \u003cp\u003eStudies meeting the following criteria were included in this review: (1) case-control or cohort epidemiological studies published as original articles; (2) the studied outcome being NPC incidence rather than mortality; (3) the association of incense or mosquito coils burning with NPC risk being examined. In the case of multiple reports on the same population, only the most recent or informative ones would be included. We only included studies which contained the minimum information necessary to estimate the odds ratio (OR) or relative risk (RR) with the reference group of non-users of incense or mosquito coils and a corresponding measure of statistical uncertainty (confidence interval [CI], standard error, variance, chi square and degree of freedom, or \u003cem\u003eP\u003c/em\u003e value, etc.) into meta-analysis.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3. Assessment of study quality\u003c/h2\u003e \u003cp\u003eThe quality of the included studies was assessed in terms of the major sources of selection bias, information bias and confounding with the help of checklists for appraising studies on risk factors developed by Yu and Tse [\u003cspan additionalcitationids=\"CR30\" citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. The essential information regarding selection retrieved from case-control studies mainly included type (whether incident/newly diagnosed) and histological confirmation of cases, source and definition of controls, and response rate; the risk of selection bias in cohort studies was mainly assessed in terms of representativeness of the cohort and the completeness and duration of the follow-up. Retrieved information regarding exposure assessment included that on the exposure period, frequency, duration, intensity and cumulative exposures. For cohort studies, risk of information bias for outcome was assessed on the method of ascertainment (independent blind assessment, record linkage, or self-reported) and whether the follow-up was long enough for NPC to occur. Comparability of cases and controls (risk of confounding) was assessed by examining what potential confounding factors have been considered and controlled for in statistical analyses.\u003c/p\u003e \u003cp\u003eThe Newcastle-Ottawa Scale (NOS) for assessing the quality of non-randomized studies in meta-analyses was also used to evaluate the quality of selected studies [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. The NOS contains eight items which are categorized into three domains, including selection of participants, comparability between groups, and assessment of exposure (case-control studies) or outcome (cohort studies). The NOS allocates stars, raging zero to nine, for quality of non-randomized studies such that studies with higher quality are scored higher stars.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4. Meta analysis\u003c/h2\u003e \u003cp\u003e The software Review Manager 5.4 was used for meta-analysis. Random-effect models were used to obtain pooled estimates of effect size and their 95% Cis. Heterogeneity across studies was assessed based on chi square tests and the \u003cem\u003eI\u003c/em\u003e\u003csup\u003e\u003cem\u003e2\u003c/em\u003e\u003c/sup\u003e index statistic. Low level of heterogeneity was defined as \u003cem\u003eI\u003c/em\u003e\u003csup\u003e\u003cem\u003e2\u003c/em\u003e\u003c/sup\u003e\u0026thinsp;\u0026le;\u0026thinsp;25%, accompanied by P\u0026thinsp;\u0026gt;\u0026thinsp;0.10 in the chi square test. Publication bias was assessed by visual inspection of funnel plots. Sensitivity analysis was conducted by removing one study at a time to examine fluctuations of the pooled effect size. A two-sided \u003cem\u003eP\u003c/em\u003e value less than 0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results","content":"\u003cp\u003eA total of 507 articles were identified in MEDLINE and Embase, and 14 additional studies were identified from reference lists of reviews and articles of interest. After a careful review of titles and abstracts, and full texts if needed, 508 articles were excluded for duplication (7), irrelevance (496), or not being cohort or case-control study (5). Finally, this systematic review included 13 individual studies, among which there were 12 case-control studies [\u003cspan additionalcitationids=\"CR19 CR20 CR21 CR22 CR23 CR24\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan additionalcitationids=\"CR34\" citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e] and 1 cohort study[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. The flow chart of study selection is illustrated in Supplemental Fig.\u0026nbsp;1. Three case-control studies were not included in further meta-analyses for associations between incense burning and NPC risk because two of them did not provide enough data to estimate effect size and uncertainty [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e] and the other one reported estimates of effect size using participants in all the other exposure groups, instead of non-users of incense, as reference [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e].\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e3.1. Cohort study\u003c/h2\u003e \u003cp\u003eOnly one previous cohort study investigated the effect of incense burning on the risk of NPC [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. This cohort study included 61 320 Singapore Chinese aged 45\u0026ndash;74 years who were recruited between 1993 and 1998 and followed up through 2005. The study quality of this study was reasonably good with NOS quality score of 8 given the methodological strengths, including representativeness of the original cohort (population-based including 85% of eligible individuals), complete follow-up (99.7%), comprehensive and prospective exposure assessment, objective assessment of outcome (91.3% histologically confirmed), and efforts to control for potential confounders (adjusting for age, gender, dialect group, education, body mass index, smoking, drinking, dietary items, and for women, parity). A total of 175 NPC cases were diagnosed during the follow-up; however, the follow-up period (12 years at most) might not be long enough for all potential NPC cases to occur. The association between incense burning and NPC risk were examined based on multiple exposure indicators and no statistically significant associations were found. The adjusted hazard ratios (HRs) for NPC were 0.7 (95% CI: 0.4\u0026ndash;1.4) in former users and 0.8 (95% CI 0.5\u0026ndash;1.3) for current uses of incense, using never users as the reference group. No exposure-response relations were observed. The HRs were 0.7 (95% CI: 0.3\u0026ndash;1.5) for less than daily current use, 1.0 (95% CI: 0.6\u0026ndash;1.7) for daily use for 40 years or less, and 1.0 (95% CI: 0.7\u0026ndash;1.4) for daily use for over 40 years.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e3.2. Case-control studies\u003c/h2\u003e \u003cp\u003eThe 12 identified case-control studies were published between 1966 and 2021, among which 11 were conducted in Chinese population of different geographic areas, including Mainland China, Hong Kong, Taiwan, and Singapore, and the remaining one was conducted in Filipinos. The number of cases ranged 47 to 2533 across individual studies. Only four studies adjusted a set of various potential confounders in multivariate analyses. The majority of these studies obtained NOS quality scores ranging 5 to 8 except for the earliest study published in 1966 with a score of 2 (Supplementary Table\u0026nbsp;2). More detailed characteristics of the 12 case-control studies are summarized in Tables\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e and \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBasic characteristics of identified case-control studies\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"9\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFirst author\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYear\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRegion\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eEthnicity\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSex (% male)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAge (year)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003ePeriod\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNo. of Cases\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNo. of Controls\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSturton\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1966\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eHong Kong\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eChinese\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eCases: 62%; controls: 35%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e70% of cases and 35% of controls were under 50 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eOct 1963 - Jun 1965\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e217\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1973\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTaiwan\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eChinese\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e73%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eCases: 46.7\u0026thinsp;\u0026plusmn;\u0026thinsp;11.5; controls: 46.2\u0026thinsp;\u0026plusmn;\u0026thinsp;11.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eDec 1969 - May 1971\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e343\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1017\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGeser\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1978\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eHong Kong\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eChinese\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e70%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e15\u0026ndash;65+;\u003c/p\u003e \u003cp\u003eMedian: cases 49.1, controls 51.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eJan 1973 - Feb 1974\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e150\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e150\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eShanmugaratnam\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1978\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSingapore\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eChinese\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eCases: 70%; controls: 64%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eCases: 10\u0026ndash;70+, median 47.4; controls: 0\u0026ndash;70+, median 46.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eMar 1966 - Aug 1968\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e379\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1639\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYu\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1986\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eHong Kong\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eChinese\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e64%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eUnder 35; cases: mean 29.2; controls: mean 28.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eFeb 1981 -\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e250\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e250\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYu\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1988\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eGuangxi, China\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eChinese\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e70%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eUnder 45; cases: mean 36.0; controls: mean 35.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eMay 1984 - Nov 1986\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e128\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e174\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYu\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1990\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eGuangzhou, China\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eChinese\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e68%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eUnder 50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eMar 1983 - Aug 1985\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e306\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e306\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWest\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1993\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePhilippine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eFilipino\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e73%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e11\u0026ndash;83, median 46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eDuration of 24 months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e104\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e208\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLee\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1994\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSingapore\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eChinese\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eCases: 73%; controls: 71%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eCases: median 37.9; controls: median 38.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eMar 1988 - Dec 1990\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e200\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e406\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHe\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2015\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eGuangdong\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eChinese\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eCases: 73.12%; controls: 70.77༅\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eCases: 46.11\u0026thinsp;\u0026plusmn;\u0026thinsp;10.99; controls: 46.42\u0026thinsp;\u0026plusmn;\u0026thinsp;11.74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eOct 2005 - Oct 2007\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1845\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e2275\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChen\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2021\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eGuangdong、Guangxi\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eChinese\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eCases: 73.4%; controls: 73.5༅\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e20\u0026ndash;74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2010\u0026ndash;2014\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e2533\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e2597\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eXie\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2014\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eHong Kong\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eChinese\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eCases: 71.9%; controls: 73.4༅\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e20\u0026ndash;75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eJun 2010-Dec 2012\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e352\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e410\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCharacteristics related to validity of identified case-control studies\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStudy\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eType of cases\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eHistological\u003c/p\u003e \u003cp\u003econfirmation\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSource of\u003c/p\u003e \u003cp\u003econtrols\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eResponse\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMatched factors\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eAdjusted factors\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSturton 1966\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN/A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eN/A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHospital\u003c/p\u003e \u003cp\u003e(cancer patients)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eN/A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eStratified by age, and sex\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLin 1973\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIncident\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e95.90%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCommunity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eCases: 91.9%; controls: 85%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSex, age, and neighborhood\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGeser 1978\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIncident\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eN/A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHospital\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eN/A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSex and age\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eShanmugaratnam 1978\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN/A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e100%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHospital\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eN/A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eAge, sex and interviewer\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYu 1986\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIncident\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e98%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCommunity (friend)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eCases: 94.0%; controls: 99.2%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSex and age\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eSalted fish intake during weaning and at age of10 year\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYu 1988\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIncident\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e100%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCommunity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eCases: 90.7%; controls: N/A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSex, age, and race\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYu 1990\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIncident\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e100%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCommunity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e100%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSex, age, and residence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eDietary factors\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWest 1993\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIncident\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e100%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTwo series: hospital and community\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eCases: 100%; hospital controls: 100%; community controls: 77%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eHospital controls: sex, age, and hospital ward type; community controls: sex, age and neighborhood\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eEducation, occupational. exposures, smoking, fresh fish and processed meat intake, and herbal medicine use\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLee 1994\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIncident\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eN/A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHospital\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eCases: 88.6%; controls: 92.5%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHe 2015\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN/A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eN/A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHospital\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eCases: 94.7%; controls༚95.5%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSex and age\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eAge、sex、education、housing type、cigarette smoking pack-years、salted fish、preserved vegetables、tea、herbal tea、slowcooked soup and family history\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChen 2021\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIncident\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e100%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCommunity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eCases: 84%; controls༚83༅\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSex, age and geographic area distribution\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eAge、sex、geographic area、education、occupation、first-degree family history、cigarette smoking、tea、oral hygiene and salt-preserved fish\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eXie 2014\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIncident\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e100%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHospital\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eCases: 94.4%; controls༚93.8༅\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAge, sex and residence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eMen:\u0026nbsp;age, smoking, environmental tobacco smokes, education, housing type, family history of NPC, intake of dark green vegetables, fruits, vitamins and supplements, drinking herbal tea, occupational exposures, and cooking experience at home; Women: age, ETS, education, and family history\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e \u003cp\u003eN/A: not available\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eEleven of the 12 studies assessed exposures to incense or mosquito coils smokes during adulthood based on usual or recent practice (4 for incense burning only, 1 for mosquito coils burning only, and 6 for both). Three of the 12 studies, all by research group of Yu et al, also assessed exposures at the age of 10 years and at birth [\u003cspan additionalcitationids=\"CR19\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. One recent study assessed exposures at the ages of 10, 18, and 30 years [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. One study assessed exposures to incense smoke during childhood but did not further clarify the specific period [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. Seven studies reported frequency data, but only one out of the twelve case-control studies considered other aspects of exposure, such as intensity and duration [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e](Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eExposure assessment in the included studies\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eStudy\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eExposure periods\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eFrequency\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eIntensity\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eDuration\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eCumulative exposure\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIncense burning\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMosquito coils burning\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCohort study\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFriborg 2008\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eat baseline\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003enot assessed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eyes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eyes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eyes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eyes\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCase-control studies\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSturton 1966\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eadulthood\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003enot assessed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eno\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eno\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eno\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eno\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLin 1973\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eadulthood\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003enot assessed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eno\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eno\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eno\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eno\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGeser 1978\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eadulthood\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003enot assessed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eno\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eno\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eno\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eno\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eShanmugaratnam 1978\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eadulthood, childhood\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003eadulthood\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eyes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eno\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eno\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eno\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYu 1986\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 years ago, age 10, at birth\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e3 years ago, age 10, at birth\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eno\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eno\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eno\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eno\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYu 1988\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eat birth, age 10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003eat birth, age 10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eyes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eno\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eno\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eno\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYu 1990\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 years ago, age 10, at birth\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e3 years ago, age 10, at birth\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eyes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eno\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eno\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eno\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWest 1993\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003enot assessed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003eadulthood\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eyes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eno\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eno\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eno\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLee 1994\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eadulthood\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003enot assessed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eno\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eno\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eno\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eno\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHe 2015\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eadulthood\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003eadulthood\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eyes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eno\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eno\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eno\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChen 2021\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAges of 10, 18 and 30, in recent 10 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003eAges of 10, 18 and 30, in recent 10 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eyes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eno\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eno\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eno\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eXie 2014\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eadulthood\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003eadulthood\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eyes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eyes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eyes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eno\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cdiv id=\"Sec10\" class=\"Section3\"\u003e \u003ch2\u003e3.2.1. Incense burning during adulthood\u003c/h2\u003e \u003cp\u003eTen previous case-control studies evaluated the associations between incense burning during adulthood and NPC risk. Among these, three studies simply reported the results as negative or not statistically significant [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e], and one study reported estimates of RRs not using non-users of incense as reference [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. The remaining 6 studies were included in meta-analysis, generating pooled OR of 1.61 (95% CI: 1.43, 1.81) in random-effect model (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ea). The heterogeneity tests suggested low heterogeneity across studies (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.39, \u003cem\u003eI\u003c/em\u003e\u003csup\u003e\u003cem\u003e2\u003c/em\u003e\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;4%). After excluding the earliest study with low quality score, the pooled OR decreased slightly to 1.58 (95% CI: 1.41, 1.78). The funnel plot suggested possible publication bias as one study with the highest OR estimate had the largest standard error (Supplemental Fig.\u0026nbsp;2), but the pooled OR did not substantially changed in sensitivity analysis excluding this specific study (Supplemental Fig.\u0026nbsp;3).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section3\"\u003e \u003ch2\u003e3.2.2. Incense burning during childhood\u003c/h2\u003e \u003cp\u003eFive previous case-control studies, including three studies from the research group of Yu et al, examined the association between incense burning at early ages and NPC risk in Chinese populations of different areas. None of them found statistically significant associations. For exposure at birth, one of these three studies only reported the results as non-significant (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.14). The pooled OR for NPC risk associated with incense burning at birth combining two studies was 1.22 (95% CI 0.76\u0026ndash;1.96) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eb). For exposure at the age of 10 years, two studies described the results as non-significant (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.34 and \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.23). The pooled OR for NPC associated with incense burning at the age of 10 years combining the other two studies was 1.37 (95% CI 1.10\u0026ndash;1.71) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ec).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section3\"\u003e \u003ch2\u003e3.2.3. Mosquito coils burning during adulthood\u003c/h2\u003e \u003cp\u003eSix previous case-control studies reported associations between mosquito coils burning during adulthood and NPC risk. One of these studies only reported the results as negative (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.39), and thus, was not included in the subsequent meta-analysis. Meta-analysis of the remaining five studies generated a pooled OR of 1.30 (95% CI 1.04\u0026ndash;1.62) in random-effects model, with substantial heterogeneity across studies (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.004, \u003cem\u003eI\u003c/em\u003e\u003csup\u003e\u003cem\u003e2\u003c/em\u003e\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;74%) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The pooled OR did not substantially changed in sensitivity analysis removing one study at each time (Supplemental Fig.\u0026nbsp;4).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section3\"\u003e \u003ch2\u003e3.2.4. Mosquito coils burning during childhood\u003c/h2\u003e \u003cp\u003eThe three case-control studies from the research group of Yu et al examined the associations between mosquito coils burning at early ages and NPC risk, and none of them reported statistically significant findings. Another recent study reported an OR of 0.84 (95% CI 0.75\u0026ndash;0.95) for NPC risk associated with mosquito coils burning in summer at the age of 10 years [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eThis updated systematic review of existing epidemiological studies investigated the associations of incense and mosquito coils burning with NPC risk. The results revealed increased risk of NPC associated with incense burning during both adulthood and childhood periods and mosquito coils burning during adulthood, but evidence regarding mosquito coils burning during childhood remains limited.\u003c/p\u003e \u003cp\u003eThe carcinogenic potentials of emissions from incense and mosquito coils burning have been intensively documented in previous literature of environmental chemistry and toxicology. Incense smoke is an important source of residential indoor PMs, including those less than 2.5\u0026micro;m in the diameter (PM\u003csub\u003e2.5\u003c/sub\u003e) which pose the largest health risks in all types of PMs [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan additionalcitationids=\"CR37 CR38 CR39\" citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]. It has been reported that incense burning produced PM over 45 mg/g burned, which was dramatically high than that burned for cigarettes (10 mg/g) [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]. Incense burning also generates various types of VOCs, including benzene, PAHs, and formaldehyde which are confirmed or probable carcinogens to humans [\u003cspan additionalcitationids=\"CR43 CR44 CR45 CR46 CR47 CR48 CR49\" citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e]. Burning of mosquito coils is also a powerful producer of carcinogenic agents, such as PAHs and formaldehyde [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. The emission of PM\u003csub\u003e2.5\u003c/sub\u003e mass from burning one mosquito coil was as high as that from burning 75\u0026ndash;137 cigarettes. Burning one mosquito coils would release the same amount of formaldehyde as that from burning 51 cigarettes [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Toxicological studies have shown that PM extracts from incense smoke is mutagenic in the Ames Salmonella test with TA98 and activation and the genotoxicity of certain incense smoke condensates in mammalian cells may be even higher than that of tobacco smoke condensates [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Given the fact that inhalation is the primary route of exposure to smokes from incense and mosquito coils burning, burning of incense and mosquito coils may be an important risk factor for malignancies in the respiratory tract including NPC.\u003c/p\u003e \u003cp\u003eThe pooled results of meta-analysis in the present study showed an increased risk of NPC associated with incense burning. However, the findings should be interpreted with caution given that publication bias was likely to be present. No associations between mosquito coils burning during childhood and the NPC risk were indicated in previous studies. It is possible to be explained by non-differential exposure misclassification regarding exposure in early life, which would have biased the results towards null, and the fact that burning mosquito coils is only an occasional practice in selective seasons, unlike incense burning which is often a long-term daily practice.\u003c/p\u003e \u003cp\u003eEpidemiological studies on health effects of environmental pollutants need accurate exposure assessment. Inaccurate exposure assessment can cause exposure misclassification, which may result in biased results and/or loss of study power, in addition to a failure in documenting a clear exposure-response relationship. Because incense and mosquito coils burning was not the primary risk factor of interest in previous case-control studies, the exposure assessment methods concerning burning of incense and mosquito coils were quite crude, e.g. only dichotomized to ever/never-exposed categories or just frequencies of burning. Only one of previous case-control studies considered other important aspects of exposure [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. In addition, these studies only used the usual (recent) burning practice for exposure assessment, though several studies also assessed exposures at early ages. Changes of behaviors over time or cumulative exposures were not considered. Even in the cohort study of reasonable study quality, the exposure assessment was based on incense burning practice at baseline only and did not adequately reflect lifetime exposure. Lack of accurate exposure assessment, particularly if non-differential, in previous studies may have diluted the observed associations between domestic incense and mosquito coils burning and NPC risk.\u003c/p\u003e \u003cp\u003eSince NPC is a relatively rare disease, cohort study design seems not an efficient method of investigation on risk factors of NPC. The reasonably large cohort study among Singapore Chinese only observed 175 NPC cases during follow-up and might not have adequate statistical power. Thus, case-control studies, especially those in high-risk regions, may continue to be the major designs in investigating the etiology of NPC due to its feasibility and efficiency.\u003c/p\u003e \u003cp\u003eThe potential risk of selection bias in this systematic review needs to be discussed hereby. A comprehensive searching strategy has been adopted to identify all published studies reporting the associations of interest. Because only a limited number of studies were specifically designed to investigate the associations of incense burning with NPC risk and the majority of these studies were published in earlier periods, several included studies were not identified through electronic searching, suggesting that electronic databases may not be sufficient for identifying studies dating back to early days. Although the original authors were also contacted for detailed information when the published results were not sufficient for meta-analysis, no additional information was obtained mainly because the data records had been destroyed after the completion of their studies. Results of the meta-analyses were probably prone to publication bias because some estimates without statistical significance were not included in meta-analyses.\u003c/p\u003e \u003cp\u003eThe validity of results in meta-analyses can be affected by that in primary studies. Although 9 of included case-control studies reported considerably high response rates, the remaining 3 did not report response rates, posing a certain risk of selection bias. Three studies did not mention whether recruited cases were incident or prevalent. If incense or mosquito coils burning is associated with poor survival of NPC patients, recruiting prevalent cases might have resulted in underestimated effects of incense or mosquito coils burning because those with poor survival, who were more likely to burn incense or mosquito coils, might have been missed. Seven studies used hospital-based controls, among which one even used cancer patients as controls [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. If control participants were diagnosed with diseases associated with incense or mosquito coils burning, the results might have been biased, for which the direction away from the true estimates depends on the specific diseases which control participants were diagnosed with. If incense or mosquito coils burning is associated with an increased risk of diseases which control participants had, the effects of incense or mosquito coils burning might have been underestimated. However, if control participants were affected by some specific diseases (e.g. asthma), they were likely to avoid exposures to smokes, which might have resulted in overestimated effects of incense or mosquito coils burning on NPC risk. Community-based controls were used in 6 of included studies. Two studies also used friend or neighborhood controls and it was possible to cause overmatching and make the estimates towards the null. In addition, even when community-based controls were used, the risk of misclassification of outcomes would be minor given that NPC is rare in the general population. Although the same methods of exposure assessment were used for cases and controls in previous studies, there remains certain risk of misclassification in previous case-control studies because of the retrospective nature of such designs. However, it was probable non-differential since incense burning and mosquito coils burning are not well-established risk factors for NPC. Hence, the resulting bias, if any, would have been towards the null. It is notable that limited efforts have been made to control for potential confounders in most of previous studies. Since incense burning is a traditional practice in some Asian populations, it is probably correlated with some other types of traditional lifestyle. Failure in controlling for potential confounding effects from other risk factors associated with traditional lifestyle may have compromised the validity of the results, leading to over- or under-estimated effects. Overall, results of meta-analyses in this systematic review were possibly subject to bias as a result of the inaccurate magnitude of association reported in the original studies that could have arisen from various sources of bias in those studies.\u003c/p\u003e"},{"header":"5. Conclusions","content":"\u003cp\u003eIn conclusion, although synthesized results of previous studies suggested an increased risk of NPC associated with incense burning and mosquito coils, existing evidence from epidemiological studies remains far from enough to accurately assess such associations. Needs are highlighted for refined exposure assessment methods, good efforts to control for confounders, and increased sample size for an adequate study power in future investigations.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eDeclaration\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eJia-Xiu Xu（First Author）:Conceptualization,Formal Analysis,Methodology,Software,Visualization,Writing-Original Draft.Lap Ah Tse:Methodology,Writing-Original Draft.Ignatius Tak-sun Yu:Methodology,Writing-Original Draft.Shao-Hua Xie(Corresponding Author):Conceptualization,Methodology,Project Administration,Supervision,Visualization,Writing-Original Draft,Writing-Review＆Editing.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eData is provided within the manuscript or supplementary information files\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eChang ET, Adami H-O. 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Gaseous Aliphatic Aldehydes in Smoke from Burning Raw Materials of Chinese Joss Sticks. Bull Environ Contam Toxicol. 1996;57(3):361\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHo SSH, Yu JZ. Concentrations of formaldehyde and other carbonyls in environments affected by incense burning. J Environ Monit. 2002;4(5):728\u0026ndash;33.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGuo Z, Jetter JJ, McBrian JA. Rates of Polycyclic Aromatic Hydrocarbon Emissions from Incense. Bull Environ Contam Toxicol. 2004;72(1):186\u0026ndash;93.\u003c/span\u003e\u003c/li\u003e \u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"incense, mosquito coils, nasopharyngeal carcinoma, systematic review, meta-analysis, risk factor","lastPublishedDoi":"10.21203/rs.3.rs-4874108/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4874108/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjectives\u003c/h2\u003e \u003cp\u003eTo clarify the association between incense and mosquito coils burning and the risk of nasopharyngeal carcinoma (NPC), we performed this systematic review of epidemiological studies.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA search of studies published through October 2022 in MEDLINE and EMBASE databases was performed, supplemented by searches of reference lists, recent reviews, and Chinese databases. The quality of the included studies was assessed with special reference to exposure assessment. Random-effect meta-analysis estimated the pooled odds ratios (OR) and 95% confidence interval (CI) whenever applicable.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eOne cohort and 12 case-control studies were identified. The cohort study found no association between incense burning and NPC risk. In meta-analysis of six case-control studies with reasonable quality, the pooled OR for incense burning during adulthood was 1.61 (95% CI 1.43\u0026ndash;1.81). Five studies assessed association between exposures to incense smoke during childhood and NPC risk, and the pooled OR was 1.22 (95% CI 0.76\u0026ndash;1.96) associated with incense burning at birth and was 1.37 (95% CI 1.10\u0026ndash;1.71) for exposure at the age of 10 years. The pooled OR for mosquito coils burning during adulthood was 1.30 (95% CI 1.04\u0026ndash;1.62). None of the four previous case-control studies found an increased risk of NPC associated with mosquito coils burning during childhood.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eOur findings suggest an increased NPC risk associated with incense burning and mosquito coils. More epidemiological studies with refined exposure assessment are still warranted.\u003c/p\u003e","manuscriptTitle":"Domestic burning of incense and mosquito coils on the risk of nasopharyngeal carcinoma: Systematic review and meta-analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-10-08 02:27:20","doi":"10.21203/rs.3.rs-4874108/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"fb16da0b-1485-4443-ba1d-003f78a63a29","owner":[],"postedDate":"October 8th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-03-31T18:38:14+00:00","versionOfRecord":[],"versionCreatedAt":"2024-10-08 02:27:20","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4874108","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4874108","identity":"rs-4874108","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}