Trends in Gastric Cancer Mortality in the US: A Population-Based Analysis, 1999-2023

Trends in Gastric Cancer Mortality in the US: A Population-Based Analysis, 1999-2023 | 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 Trends in Gastric Cancer Mortality in the US: A Population-Based Analysis, 1999-2023 Sardar Muhammad Imran Khan, Hafsa Shahid, Noor Fatima, Muneeb Khawar, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6327806/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 Purpose Gastric cancer is a leading cause of mortality worldwide, with pronounced variations in outcomes across populations. This study investigates U.S. trends in age-adjusted mortality rates (AAMRs) for gastric cancer from 1999 to 2023, examining differences by sex, race, region, and urbanization to uncover critical patterns and inequities. Methods Data were extracted from the CDC WONDER database using ICD-10 code C16 to identify gastric cancer-related deaths in adults aged 25 and older. AAMRs per 1,000,000 population were calculated and stratified by year, sex, race/ethnicity, geographic region, and urban-rural classification. Trends were analyzed using Joinpoint regression to determine annual percentage changes (APC) and 95% confidence intervals (CI). Statistical significance was set at p < 0.05. Results From 1999 to 2023, there were 312,300 gastric cancer deaths (185,391 men, 126,909 women). Overall, AAMRs declined consistently, with APCs of -3.4 for the period 1999 to 2007, -2.2 for 2007 to 2018, and − 1.2 for 2018 to 2023. Men showed a more pronounced decline, with APCs of -3.6 for 1999 to 2009 and − 2.2 for 2009 to 2023, compared to women, who had APCs of -3.1 for 1999 to 2008, -1.9 for 2008 to 2018, and − 0.8 for 2018 to 2023. Non-Hispanic Black populations experienced a decline in AAMR with an APC of -3.3 for 1999 to 2020, while Hispanic/Latino and Asian/Pacific Islander populations showed declines with APCs of -2.8 for 1999 to 2011 and − 3.8 for 1999 to 2020, respectively. Metropolitan areas saw AAMR reductions with APCs of -3.3 for 1999 to 2008 and − 2.2 for 2008 to 2020, while non-metropolitan areas had larger initial declines with an APC of -3.6 for 1999 to 2006 but slower decreases with an APC of -2.0 for 2006 to 2020. Geographically, the Northeast had the highest AAMR (62.9), followed by the West (61.7), South (57.4), and Midwest (50.9). Hawaii recorded the highest state-level AAMR (96.5), while Wyoming had the lowest (36.6). States in the top 90th percentile included Alaska, California, and New York, whereas Utah, Idaho, and Iowa were among the lowest. Conclusion Gastric cancer mortality in the U.S. has declined over the past two decades, but the pace of reduction has slowed in recent years. Significant disparities persist across sex, racial, and geographic groups, underscoring the need for targeted interventions to address these inequities and improve outcomes in vulnerable populations. Temporal trends Gastric Cancer USA population Figures Figure 1 Figure 2 Figure 3 Figure 4 INTRODUCTION Gastric cancer affects over 1 million people worldwide each year, making it a major global health challenge despite medical advancements.( 1 ) This malignancy ranks as the fifth most common cancer globally and the third leading cause of cancer-related deaths.( 2 ) In the United States, while gastric cancer accounts for a smaller proportion of cancer cases, its impact on public health remains significant. Understanding the trends in its incidence and mortality is crucial for developing effective prevention and treatment strategies. Recent studies have shown a decline in age-standardized death rates, reflecting improvements in early detection and treatment.( 3 ) However, certain regions continue to experience high death rates.( 4 ) In the United States, the incidence of gastric cancer has decreased significantly from 1975 to 2020, with a notable reduction in deaths as well.( 5 ) Despite these overall declines, younger individuals and certain ethnic groups, have shown increasing trends.( 6 ) It is predicted that while mortality rates may continue to decline in most countries, the absolute number of deaths could rise due to population growth.( 7 ) Although gastric cancer mortality rates in the U.S. have generally decreased, the pace of reduction in the number of deaths has slowed in recent years, and significant disparities persist across sex, racial, and geographic groups.( 5 , 8 ) This highlights a critical gap in the existing literature, as there is limited data addressing the differences in mortality trends among these subpopulations. The research problem, therefore, lies in the limited understanding of the factors contributing to these disparities and the slowing decline in mortality rates. To address this gap, our study aims to provide a comprehensive analysis of the trends in age-adjusted mortality rates (AAMRs) for gastric cancer in the U.S. from 1999 to 2023. Specifically, we will examine differences by sex, race/ethnicity, geographic region, and urban-rural classification to uncover critical patterns and inequities. By identifying these trends and disparities, our objective is to inform targeted interventions and policies that can effectively address these inequities and improve outcomes for vulnerable populations. METHODS Study design and population This descriptive study used the CDC WONDER (Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research) database to gather data.( 9 ) It focused on the mortality associated with gastric cancer in adults from 1999 to 2023, using the ICD-10 code C16 to identify relevant cases. Mortality data related to gastric cancer were extracted from the Multiple Causes of Death Public Use Death Certificates. The study sample included adults aged 25 and older at the time of death. As the research relied on publicly available government data, institutional review board approval was not necessary. The dataset included cause-of-death information from death certificates across all 50 states and the District of Columbia. The study followed the STROBE guidelines.( 10 ) Data extraction Population characteristics, including size, demographics, urban-rural classification, census region, and states, were extracted for this analysis. Demographic information related to sex and overall trends was collected for the years 1999 to 2023, while data on race, census region, urban-rural classification, states, and age groups was gathered for 1999 to 2020. The race and ethnicity categories included Non-Hispanic (NH) White, NH Black or African American, Hispanic or Latino, NH American Indian or Alaskan Native, and NH Asian or Pacific Islander. Urban-rural classification followed the 2013 U.S. urbanization criteria: areas with populations over one million were designated as major metropolitan, areas with populations between 50,000 and 999,999 as medium or small metropolitan, and those with fewer than 50,000 people as rural.( 11 ) The regional classification followed the U.S. Census Bureau's divisions into Northeast, Midwest, South, and West. Statistical analysis For this analysis, we calculated Age-Adjusted Mortality Rates (AAMRs) per 1000,000 individuals, categorized by year, sex, race or ethnicity, state, and urban-rural classification, along with their 95% confidence intervals (CIs). These AAMRs were determined by comparing gastric cancer deaths to the U.S. 2000 standard population.( 12 ) To examine trends in mortality, we employed the Joinpoint Regression Program (Joinpoint V 5.0.2, National Cancer Institute) to compute the Annual Percent Change (APC) and its 95% CIs for AAMRs. This allowed us to track national trends in gastric cancer mortality.( 13 ) Statistical significance of the APC slopes was tested using two-tailed t-tests to assess whether changes in mortality rates were significantly different from zero. When a statistically significant slope (p-value < 0.05) was observed, the APC was classified as either increasing or decreasing for that period of research study. RESULTS Mortality rates across various demographic groups revealed notable trends throughout the study period. From 1999 to 2023, a total of 312,300 adult deaths (age 25–85+) were attributed to gastric cancer. Of these, 185,391 deaths occurred in men, while 126,909 deaths were recorded in women during the same period (Supplemental Table 1). When stratified by race and ethnicity, from 1999 to 2020, the total number of deaths was as follows: Indigenous populations, including American Indian and Alaska Native individuals, accounted for 2,036 deaths; Asian and Pacific Islander populations experienced 18,566 deaths; Black or African American individuals had 47,570 deaths; White individuals had 171,914 deaths; and Hispanic or Latino populations recorded 35,331 deaths (Supplemental Table 2). Overall, the AAMR showed a consistent decline, with an APC of -3.4 (95% CI: -4.6 to -2.9) from 1999 to 2007, followed by a slower reduction of -2.2 (95% CI: -3.5 to -1.8) from 2007 to 2018 and an even slower decline of -1.2 (95% CI: -2.0 to 0.3) from 2018 to 2023 (Supplemental table 3 and Fig. 1 ). Sex Disparities Between 1999 and 2009, the age-adjusted mortality rate (AAMR) for men declined by - 3.6 (95% CI: -4.0 to -3.3). This decrease continued at a slower rate of -2.2 (95% CI: -2.4 to -2.0) from 2009 to 2023 ( Fig. 1 ) . In contrast, women experienced a slightly smaller overall reduction, with an average annual percentage change (APC) of - 3.1 (95% CI: -4.3 to -2.7) from 1999 to 2008. The decline continued at - 1.9 (95% CI: -3.4 to -1.5) from 2008 to 2018. However, from 2018 to 2023, the trend remained stable ( -0.8, 95% CI: -1.6 to 1.0), indicating little to no significant change during this period. Racial Disparities Among non-Hispanic Black or African American populations, the AAMR declined by - 3.3 (95% CI: -3.5 to -3.0) from 1999 to 2020 ( Fig. 2 , Supplemental Table 4) . Similarly, the non-Hispanic White population exhibited a decline from 1999 to 2008 at an APC of - 3.7 (95% CI: -5.0 to -1.7). However, the rate of decline slowed between 2008 and 2018, with an APC of -2.7 (95% CI: -4.8 to -1.9), followed by a stable trend (-0.7, 95% CI: -2.7 to 0.6) from 2018 onward. The Hispanic or Latino population experienced a decrease of -2.8 (95% CI: -4.4 to -2.4) between 1999 and 2011, followed by a consistent trend (-1.7, 95% CI: -2.1 to 0.2) from 2011 to 2020, suggesting little fluctuation in AAMR during this period. For the American Indian or Alaska Native population, the AAMR declined at an APC of -2.2 (95% CI: -3.0 to -1.3) from 1999 to 2020. The Asian or Pacific Islander population experienced a steady reduction of - 3.8 (95% CI: -4.1 to -3.6) over the same period. Urban-Rural Disparities In metropolitan areas, the AAMR declined by - 3.3 (95% CI: -4.6 to -2.9) from 1999 to 2008, followed by a slower reduction of - 2.2 (95% CI: -2.5 to -1.4) from 2008 to 2020 (Supplemental Table 5 , Fig. 3 ) .Non-metropolitan areas saw a steeper initial decline of - 3.6 (95% CI: -6.4 to -2.7) from 1999 to 2006, but the rate slowed to - 2.0 (95% CI: -2.3 to -0.8) between 2006 and 2020. Census region Disparities The Northeast region experienced an APC of - 3.9 (95% CI: -4.5 to -3.6) from 1999 to 2010, followed by a slower decline of - 2.3 (95% CI: -2.8 to -1.6) from 2010 to 2020 ( Fig. 4 , Supplemental Table 6) .In the Midwest, the AAMR declined at - 3.5 (95% CI: -5.3 to -2.9) from 1999 to 2006 and slowed to - 2.5 (95% CI: -2.7 to -1.5) from 2006 to 2020.A similar trend was observed in the South, where the AAMR declined at - 3.3 (95% CI: -5.9 to -2.5) from 1999 to 2006, followed by a slower decline of - 1.9 (95% CI: -2.2 to -0.7) between 2006 and 2020.The West exhibited the slowest reduction, with an APC of - 3.1 (95% CI: -5.7 to -2.5) from 1999 to 2008. Between 2008 and 2020, the decline slowed further to - 1.8 (95% CI: -2.2 to 0.2), suggesting a stable trend with no significant reduction in AAMR during this period. State-Level Disparities Among all U.S. states, Hawaii had the highest AAMR at 96.5 (95% CI: 92.4–100.5), while Wyoming had the lowest at 36.6 (95% CI: 32.4–40.8) (Supplemental Table 7) .In the 90th percentile for AAMR, states with the highest rates included Alaska (71.3), California (72.8), the District of Columbia (87.2), and New York (70.6). Conversely, states in the lowest 10th percentile indicating the best overall AAMR outcomes were Utah (39.1), Idaho (40.0), Iowa (40.8), and Montana (41.0). DISCUSSION This study aimed to highlight the mortality trends of gastric cancer in the US from 1999 to 2023. There were found to be 312,300 deaths from gastric cancer in adults aged 25 years and older during this period. This study demonstrated an overall decline in mortality across all geographical and racial groups. Key significant findings included increased mortality in men as compared to women and in the non-Hispanic White population. The reasons why mortality is predominant in men are likely multifactorial, but it is thought that men may have more risk factors for gastric cancer which encompass the use of tobacco, poor hygiene and, dietary differences including lower consumption of fruits and vegetables which have shown a reduction over time.( 14 ) Overall, the age-adjusted mortality rate showed a steeper decline from 1997 to 2007, followed by a slower decrease in the subsequent years. This trend is likely influenced by multiple factors, including a reduction in Helicobacter pylori (H. pylori) infection, a major known cause of gastric cancer. Studies have shown that the decline in H. pylori infection has paralleled the decrease in gastric cancer incidence.( 15 ) Other key contributors to this trend include improved food preservation, better dietary habits, and advancements in medical treatment. Ongoing research on treatment strategies in oncology has also played a significant role in reducing mortality rates.( 16 ) There were some marked disparities observed in the racial and ethnic sub-populations. Hispanic/Latino and American Indian/Alaskan Native populations showed slower decline comparatively which may be explained by barriers in access to healthcare and availability of health insurance. In addition, the low economic income settings, decreased health literacy and limited access to medical care may increase the spread of risk factors for gastric cancer.( 17 ) This further signifies the importance of targeted efforts to reduce the disease burden in these vulnerable populations. Mortality rates are higher in certain U.S. states, such as Hawaii and California, due to the larger Asian and Asian Pacific Islander populations. This group has a greater genetic predisposition to gastric cancer, along with higher exposure to risk factors such as increased salt intake and H. Pylori infection. These findings are consistent with those found in 2003 and 2010, that gastric cancer is most prevalent in the Hawaii Area (11.9 and 9.2 per 100,000 persons, respectively).( 18 ) Although no specific reason has been found for this association, it can be because of several local and regional factors. Gastric cancer mortality trends since 1999 show diverging patterns between urban and rural areas, with metropolitan regions experiencing relative increases compared to rural zones. While mortality rates have declined overall in both settings—falling 1.96% annually in urban areas versus 1.43% in rural areas (1999–2020)—the urban-rural gap has widened due to distinct risk profiles. Key drivers of metropolitan increase include dietary factors such as frequent consumption of fried foods (linked to 52% elevated cancer risk) and processed meats, compounded by urban food environments favoring fast-food density.( 19 ) Rural declines, while slower, reflect improved access to Helicobacter pylori screening and reduced tobacco use. Shared improvements stem from nationwide advancements in endoscopic surveillance, minimally invasive surgeries, and targeted therapies. This article also presents gastric cancer-related age-adjusted mortality rates per 100,000 adults stratified by U.S. Census region from 1999 to 2020. The data reveals distinct regional disparities, with the highest mortality rates observed in the western region since 2009, compared to the Northeast region from 2000 to 2009, when compared to other regions. Over the 21 years, all regions showed a gradual decline in mortality rates, though the pace of reduction varied geographically. This pattern likely reflects differences in risk factor prevalence (such as smoking rates, dietary habits, and Helicobacter pylori infection), healthcare access disparities, and regional variations in early detection programs. The West's persistently elevated rates for the last decade may correlate with higher rates of obesity and processed meat consumption, while the Midwest's lower mortality could be attributed to demographic factors and earlier adoption of cancer screening protocols. The convergence of mortality trends across regions in later years suggests potential nationwide improvements in treatment modalities and public health interventions.( 20 ) Although gastric cancer mortality rates are declining across the U.S., the disease remains a significant concern. It is crucial to explore prevention and early detection strategies, similar to those implemented in countries like Japan, Korea, and China, where gastric cancer incidence is higher than in the U.S. Additionally, further research is needed to understand the underlying causes of these disparities, allowing for targeted interventions while also advancing cancer treatment strategies. Declarations Acknowledgement Open Access provided by Qatar National Library Author Contribution Statement S.M.I.K. and H.S. conceptualized the study and developed the study design. N.F. and M.K. contributed to the data extraction and initial analysis. M.W. and A.R. performed the statistical analysis and created the tables. M.I.S. and A.Q. reviewed and contributed to the methodology and interpretation of results. J.I. supervised the analysis and drafted the manuscript. All authors reviewed and provided critical revisions to the manuscript. Funding Statement: This analysis was conducted without any specific financial support or sponsorship. Open Access funding support is acknowledged from Qatar National Library. Conflict of Interest Disclosure: The authors declare no competing financial interests or personal relationships that could have influenced the findings or conclusions of this analysis. Ethics Approval Statement: This CDC analysis is based solely on publicly available data and did not involve direct research with human participants or animals. Therefore, ethical approval was not required. Patient Consent Statement: This analysis does not include direct patient involvement or identifiable personal data; patient consent was not required. Permission to Reproduce Material from Other Sources: No copyrighted material requiring permission for reproduction was used in this analysis. Consent to Publish declaration: Not Applicable Consent to Participate declaration: Not Applicable Trial registration number: Not Applicable References Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018 Nov;68(6):394–424. Nishimuni M, Claro LCL, Braghiroli MIFM. Advancements and challenges in gastric cancer: epidemiology, biomarkers, and therapeutic strategies. Surg Exp Pathol. 2024 Sep 27;7(1):19. Tan N, Wu H, Cao M, Yang F, Yan X, He S, et al. Global, regional, and national burden of early-onset gastric cancer. Cancer Biol Med. 2024 Aug 7;21(8):667–78. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020 Jan;70(1):7–30. Wong MCS, Huang J, Chan PSF, Choi P, Lao XQ, Chan SM, et al. Global Incidence and Mortality of Gastric Cancer, 1980-2018. JAMA Netw Open. 2021 Jul 1;4(7):e2118457. Holowatyj AN, Ulrich CM, Lewis MA. Racial/Ethnic Patterns of Young-Onset Noncardia Gastric Cancer. Cancer Prev Res Phila Pa. 2019 Nov;12(11):771–80. Lin JL, Lin JX, Lin GT, Huang CM, Zheng CH, Xie JW, et al. Global incidence and mortality trends of gastric cancer and predicted mortality of gastric cancer by 2035. BMC Public Health. 2024 Jul 2;24(1):1763. Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA Cancer J Clin. 2022 Jan;72(1):7–33. Multiple Cause of Death, 1999-2020 Request [Internet]. [cited 2025 Feb 4]. Available from: https://wonder.cdc.gov/mcd-icd10.html von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP, et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. J Clin Epidemiol. 2008 Apr;61(4):344–9. Ingram DD, Franco SJ. 2013 NCHS Urban-Rural Classification Scheme for Counties. Vital Health Stat 2. 2014 Apr;(166):1–73. Anderson RN, Rosenberg HM. Age standardization of death rates: implementation of the year 2000 standard. Natl Vital Stat Rep Cent Dis Control Prev Natl Cent Health Stat Natl Vital Stat Syst. 1998 Oct 7;47(3):1–16, 20. Joinpoint Regression Program [Internet]. [cited 2025 Feb 4]. Available from: https://surveillance.cancer.gov/joinpoint/ Torres-Roman JS, Alvarez CS, Guerra-Canchari P, Valcarcel B, Martinez-Herrera JF, Dávila-Hernández CA, et al. Sex and age differences in mortality trends of gastric cancer among Hispanic/Latino populations in the United States, Latin America, and the Caribbean. Lancet Reg Health Am. 2022 Dec;16:100376. Axon A. Helicobacter pylori: what do we still need to know? J Clin Gastroenterol. 2006 Jan;40(1):15–9. Verdecchia A, Corazziari I, Gatta G, Lisi D, Faivre J, Forman D, et al. Explaining gastric cancer survival differences among European countries. Int J Cancer. 2004 May 1;109(5):737–41. Torres J, Correa P, Ferreccio C, Hernandez-Suarez G, Herrero R, Cavazza-Porro M, et al. Gastric cancer incidence and mortality is associated with altitude in the mountainous regions of Pacific Latin America. Cancer Causes Control CCC. 2013 Feb;24(2):249–56. Thrift AP, El-Serag HB. Burden of Gastric Cancer. Clin Gastroenterol Hepatol Off Clin Pract J Am Gastroenterol Assoc. 2020 Mar;18(3):534–42. Ngoan LT, Mizoue T, Fujino Y, Tokui N, Yoshimura T. Dietary factors and stomach cancer mortality. Br J Cancer. 2002 Jul 1;87(1):37–42. Song Y, Liu X, Cheng W, Li H, Zhang D. The global, regional and national burden of stomach cancer and its attributable risk factors from 1990 to 2019. Sci Rep. 2022 Jul 7;12(1):11542. Additional Declarations No competing interests reported. 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2","display":"","copyAsset":false,"role":"figure","size":429878,"visible":true,"origin":"","legend":"\u003cp\u003eGastric cancer–related Age adjusted mortality rate per 1000,000, stratified by race among Adults in the United States from 1999 to 2020\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-6327806/v1/e4c27b25bdbe9de0ceabd550.png"},{"id":82593750,"identity":"937f70ad-7b61-4261-a483-84625cf85b7b","added_by":"auto","created_at":"2025-05-13 08:26:13","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":239013,"visible":true,"origin":"","legend":"\u003cp\u003eGastric cancer –related Age adjusted mortality rate per 1000,000, stratified by urban-rural among Adults in the United States from 1999 to 2020\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-6327806/v1/3737717fb009c889bdedd68e.png"},{"id":82592515,"identity":"095a759e-840c-4093-b8a3-288438d9e35c","added_by":"auto","created_at":"2025-05-13 08:18:13","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":363752,"visible":true,"origin":"","legend":"\u003cp\u003eGastric cancer –related Age adjusted mortality rate per 1000,000, stratified by Census region among Adults in the United States from 1999 to 2020\u003c/p\u003e","description":"","filename":"Figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-6327806/v1/36ab325f4cb2ccba86e58c9c.png"},{"id":87513509,"identity":"b3fe4dc1-e6b0-4ee0-aa7a-f44f3766535d","added_by":"auto","created_at":"2025-07-24 16:01:45","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1971581,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6327806/v1/eb2034e1-2a08-4a51-a42c-2d0d3552ee05.pdf"},{"id":82592511,"identity":"92c084f3-2489-46a0-b792-765e9c74bdc3","added_by":"auto","created_at":"2025-05-13 08:18:13","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":34753,"visible":true,"origin":"","legend":"","description":"","filename":"gastriccasupptable3.docx","url":"https://assets-eu.researchsquare.com/files/rs-6327806/v1/450252ac74b9af00c2aa9e0b.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eTrends in Gastric Cancer Mortality in the US: A Population-Based Analysis, 1999-2023\u003c/p\u003e","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eGastric cancer affects over 1\u0026nbsp;million people worldwide each year, making it a major global health challenge despite medical advancements.(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) This malignancy ranks as the fifth most common cancer globally and the third leading cause of cancer-related deaths.(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) In the United States, while gastric cancer accounts for a smaller proportion of cancer cases, its impact on public health remains significant. Understanding the trends in its incidence and mortality is crucial for developing effective prevention and treatment strategies.\u003c/p\u003e \u003cp\u003eRecent studies have shown a decline in age-standardized death rates, reflecting improvements in early detection and treatment.(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) However, certain regions continue to experience high death rates.(\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) In the United States, the incidence of gastric cancer has decreased significantly from 1975 to 2020, with a notable reduction in deaths as well.(\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e) Despite these overall declines, younger individuals and certain ethnic groups, have shown increasing trends.(\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e) It is predicted that while mortality rates may continue to decline in most countries, the absolute number of deaths could rise due to population growth.(\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eAlthough gastric cancer mortality rates in the U.S. have generally decreased, the pace of reduction in the number of deaths has slowed in recent years, and significant disparities persist across sex, racial, and geographic groups.(\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e) This highlights a critical gap in the existing literature, as there is limited data addressing the differences in mortality trends among these subpopulations. The research problem, therefore, lies in the limited understanding of the factors contributing to these disparities and the slowing decline in mortality rates.\u003c/p\u003e \u003cp\u003eTo address this gap, our study aims to provide a comprehensive analysis of the trends in age-adjusted mortality rates (AAMRs) for gastric cancer in the U.S. from 1999 to 2023. Specifically, we will examine differences by sex, race/ethnicity, geographic region, and urban-rural classification to uncover critical patterns and inequities. By identifying these trends and disparities, our objective is to inform targeted interventions and policies that can effectively address these inequities and improve outcomes for vulnerable populations.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design and population\u003c/h2\u003e \u003cp\u003eThis descriptive study used the CDC WONDER (Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research) database to gather data.(\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e) It focused on the mortality associated with gastric cancer in adults from 1999 to 2023, using the ICD-10 code C16 to identify relevant cases. Mortality data related to gastric cancer were extracted from the Multiple Causes of Death Public Use Death Certificates. The study sample included adults aged 25 and older at the time of death. As the research relied on publicly available government data, institutional review board approval was not necessary. The dataset included cause-of-death information from death certificates across all 50 states and the District of Columbia. The study followed the STROBE guidelines.(\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e)\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eData extraction\u003c/h3\u003e\n\u003cp\u003ePopulation characteristics, including size, demographics, urban-rural classification, census region, and states, were extracted for this analysis. Demographic information related to sex and overall trends was collected for the years 1999 to 2023, while data on race, census region, urban-rural classification, states, and age groups was gathered for 1999 to 2020. The race and ethnicity categories included Non-Hispanic (NH) White, NH Black or African American, Hispanic or Latino, NH American Indian or Alaskan Native, and NH Asian or Pacific Islander.\u003c/p\u003e \u003cp\u003eUrban-rural classification followed the 2013 U.S. urbanization criteria: areas with populations over one million were designated as major metropolitan, areas with populations between 50,000 and 999,999 as medium or small metropolitan, and those with fewer than 50,000 people as rural.(\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e) The regional classification followed the U.S. Census Bureau's divisions into Northeast, Midwest, South, and West.\u003c/p\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eFor this analysis, we calculated Age-Adjusted Mortality Rates (AAMRs) per 1000,000 individuals, categorized by year, sex, race or ethnicity, state, and urban-rural classification, along with their 95% confidence intervals (CIs). These AAMRs were determined by comparing gastric cancer deaths to the U.S. 2000 standard population.(\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eTo examine trends in mortality, we employed the Joinpoint Regression Program (Joinpoint V 5.0.2, National Cancer Institute) to compute the Annual Percent Change (APC) and its 95% CIs for AAMRs. This allowed us to track national trends in gastric cancer mortality.(\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e) Statistical significance of the APC slopes was tested using two-tailed t-tests to assess whether changes in mortality rates were significantly different from zero. When a statistically significant slope (p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05) was observed, the APC was classified as either increasing or decreasing for that period of research study.\u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003cp\u003eMortality rates across various demographic groups revealed notable trends throughout the study period. From 1999 to 2023, a total of 312,300 adult deaths (age 25\u0026ndash;85+) were attributed to gastric cancer. Of these, 185,391 deaths occurred in men, while 126,909 deaths were recorded in women during the same period \u003cb\u003e(Supplemental Table\u0026nbsp;1).\u003c/b\u003e When stratified by race and ethnicity, from 1999 to 2020, the total number of deaths was as follows: Indigenous populations, including American Indian and Alaska Native individuals, accounted for 2,036 deaths; Asian and Pacific Islander populations experienced 18,566 deaths; Black or African American individuals had 47,570 deaths; White individuals had 171,914 deaths; and Hispanic or Latino populations recorded 35,331 deaths \u003cb\u003e(Supplemental Table\u0026nbsp;2).\u003c/b\u003e\u003c/p\u003e \u003cp\u003eOverall, the AAMR showed a consistent decline, with an APC of -3.4 (95% CI: -4.6 to -2.9) from 1999 to 2007, followed by a slower reduction of -2.2 (95% CI: -3.5 to -1.8) from 2007 to 2018 and an even slower decline of -1.2 (95% CI: -2.0 to 0.3) from 2018 to 2023 \u003cb\u003e(Supplemental table 3 and\u003c/b\u003e Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u003cb\u003e).\u003c/b\u003e\u003c/p\u003e \u003cp\u003e \u003c/p\u003e\n\u003ch3\u003eSex Disparities\u003c/h3\u003e\n\u003cp\u003eBetween 1999 and 2009, the age-adjusted mortality rate (AAMR) for men declined by \u003cb\u003e-\u003c/b\u003e3.6 (95% CI: -4.0 to -3.3). This decrease continued at a slower rate of -2.2 (95% CI: -2.4 to -2.0) from 2009 to 2023 \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e.\u003c/p\u003e \u003cp\u003eIn contrast, women experienced a slightly smaller overall reduction, with an average annual percentage change (APC) of \u003cb\u003e-\u003c/b\u003e3.1 (95% CI: -4.3 to -2.7) from 1999 to 2008. The decline continued at \u003cb\u003e-\u003c/b\u003e1.9 (95% CI: -3.4 to -1.5) from 2008 to 2018. However, from 2018 to 2023, the trend remained stable \u003cb\u003e(\u003c/b\u003e-0.8, 95% CI: -1.6 to 1.0), indicating little to no significant change during this period.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eRacial Disparities\u003c/h2\u003e \u003cp\u003eAmong non-Hispanic Black or African American populations, the AAMR declined by \u003cb\u003e-\u003c/b\u003e3.3 (95% CI: -3.5 to -3.0) from 1999 to 2020 \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, \u003cb\u003eSupplemental Table\u0026nbsp;4)\u003c/b\u003e. Similarly, the non-Hispanic White population exhibited a decline from 1999 to 2008 at an APC of \u003cb\u003e-\u003c/b\u003e3.7 (95% CI: -5.0 to -1.7). However, the rate of decline slowed between 2008 and 2018, with an APC of \u003cb\u003e-2.7\u003c/b\u003e (95% CI: -4.8 to -1.9), followed by a stable trend (-0.7, 95% CI: -2.7 to 0.6) from 2018 onward. The Hispanic or Latino population experienced a decrease of -2.8 (95% CI: -4.4 to -2.4) between 1999 and 2011, followed by a consistent trend (-1.7, 95% CI: -2.1 to 0.2) from 2011 to 2020, suggesting little fluctuation in AAMR during this period. For the American Indian or Alaska Native population, the AAMR declined at an APC of -2.2 (95% CI: -3.0 to -1.3) from 1999 to 2020. The Asian or Pacific Islander population experienced a steady reduction of \u003cb\u003e-\u003c/b\u003e3.8 (95% CI: -4.1 to -3.6) over the same period.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eUrban-Rural Disparities\u003c/h3\u003e\n\u003cp\u003eIn metropolitan areas, the AAMR declined by \u003cb\u003e-\u003c/b\u003e3.3 (95% CI: -4.6 to -2.9) from 1999 to 2008, followed by a slower reduction of \u003cb\u003e-\u003c/b\u003e2.2 (95% CI: -2.5 to -1.4) from 2008 to 2020 \u003cb\u003e(Supplemental Table\u0026nbsp;5\u003c/b\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e.Non-metropolitan areas saw a steeper initial decline of \u003cb\u003e-\u003c/b\u003e3.6 (95% CI: -6.4 to -2.7) from 1999 to 2006, but the rate slowed to \u003cb\u003e-\u003c/b\u003e2.0 (95% CI: -2.3 to -0.8) between 2006 and 2020.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e\n\u003ch3\u003eCensus region Disparities\u003c/h3\u003e\n\u003cp\u003eThe Northeast region experienced an APC of \u003cb\u003e-\u003c/b\u003e3.9 (95% CI: -4.5 to -3.6) from 1999 to 2010, followed by a slower decline of \u003cb\u003e-\u003c/b\u003e2.3 (95% CI: -2.8 to -1.6) from 2010 to 2020 \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e, \u003cb\u003eSupplemental Table\u0026nbsp;6)\u003c/b\u003e.In the Midwest, the AAMR declined at \u003cb\u003e-\u003c/b\u003e3.5 (95% CI: -5.3 to -2.9) from 1999 to 2006 and slowed to \u003cb\u003e-\u003c/b\u003e2.5 (95% CI: -2.7 to -1.5) from 2006 to 2020.A similar trend was observed in the South, where the AAMR declined at \u003cb\u003e-\u003c/b\u003e3.3 (95% CI: -5.9 to -2.5) from 1999 to 2006, followed by a slower decline of \u003cb\u003e-\u003c/b\u003e1.9 (95% CI: -2.2 to -0.7) between 2006 and 2020.The West exhibited the slowest reduction, with an APC of \u003cb\u003e-\u003c/b\u003e3.1 (95% CI: -5.7 to -2.5) from 1999 to 2008. Between 2008 and 2020, the decline slowed further to \u003cb\u003e-\u003c/b\u003e1.8 (95% CI: -2.2 to 0.2), suggesting a stable trend with no significant reduction in AAMR during this period.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eState-Level Disparities\u003c/h2\u003e \u003cp\u003eAmong all U.S. states, Hawaii had the highest AAMR at 96.5 (95% CI: 92.4\u0026ndash;100.5), while Wyoming had the lowest at 36.6 (95% CI: 32.4\u0026ndash;40.8) \u003cb\u003e(Supplemental Table\u0026nbsp;7)\u003c/b\u003e.In the 90th percentile for AAMR, states with the highest rates included Alaska (71.3), California (72.8), the District of Columbia (87.2), and New York (70.6). Conversely, states in the lowest 10th percentile indicating the best overall AAMR outcomes were Utah (39.1), Idaho (40.0), Iowa (40.8), and Montana (41.0).\u003c/p\u003e \u003c/div\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThis study aimed to highlight the mortality trends of gastric cancer in the US from 1999 to 2023. There were found to be 312,300 deaths from gastric cancer in adults aged 25 years and older during this period. This study demonstrated an overall decline in mortality across all geographical and racial groups. Key significant findings included increased mortality in men as compared to women and in the non-Hispanic White population.\u003c/p\u003e \u003cp\u003eThe reasons why mortality is predominant in men are likely multifactorial, but it is thought that men may have more risk factors for gastric cancer which encompass the use of tobacco, poor hygiene and, dietary differences including lower consumption of fruits and vegetables which have shown a reduction over time.(\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eOverall, the age-adjusted mortality rate showed a steeper decline from 1997 to 2007, followed by a slower decrease in the subsequent years. This trend is likely influenced by multiple factors, including a reduction in Helicobacter pylori (H. pylori) infection, a major known cause of gastric cancer. Studies have shown that the decline in H. pylori infection has paralleled the decrease in gastric cancer incidence.(\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e) Other key contributors to this trend include improved food preservation, better dietary habits, and advancements in medical treatment. Ongoing research on treatment strategies in oncology has also played a significant role in reducing mortality rates.(\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eThere were some marked disparities observed in the racial and ethnic sub-populations. Hispanic/Latino and American Indian/Alaskan Native populations showed slower decline comparatively which may be explained by barriers in access to healthcare and availability of health insurance. In addition, the low economic income settings, decreased health literacy and limited access to medical care may increase the spread of risk factors for gastric cancer.(\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e) This further signifies the importance of targeted efforts to reduce the disease burden in these vulnerable populations.\u003c/p\u003e \u003cp\u003eMortality rates are higher in certain U.S. states, such as Hawaii and California, due to the larger Asian and Asian Pacific Islander populations. This group has a greater genetic predisposition to gastric cancer, along with higher exposure to risk factors such as increased salt intake and H. Pylori infection. These findings are consistent with those found in 2003 and 2010, that gastric cancer is most prevalent in the Hawaii Area (11.9 and 9.2 per 100,000 persons, respectively).(\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e) Although no specific reason has been found for this association, it can be because of several local and regional factors.\u003c/p\u003e \u003cp\u003eGastric cancer mortality trends since 1999 show diverging patterns between urban and rural areas, with metropolitan regions experiencing relative increases compared to rural zones. While mortality rates have declined overall in both settings\u0026mdash;falling 1.96% annually in urban areas versus 1.43% in rural areas (1999\u0026ndash;2020)\u0026mdash;the urban-rural gap has widened due to distinct risk profiles. Key drivers of metropolitan increase include dietary factors such as frequent consumption of fried foods (linked to 52% elevated cancer risk) and processed meats, compounded by urban food environments favoring fast-food density.(\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e) Rural declines, while slower, reflect improved access to Helicobacter pylori screening and reduced tobacco use. Shared improvements stem from nationwide advancements in endoscopic surveillance, minimally invasive surgeries, and targeted therapies.\u003c/p\u003e \u003cp\u003eThis article also presents gastric cancer-related age-adjusted mortality rates per 100,000 adults stratified by U.S. Census region from 1999 to 2020. The data reveals distinct regional disparities, with the highest mortality rates observed in the western region since 2009,\u003c/p\u003e \u003cp\u003ecompared to the Northeast region from 2000 to 2009, when compared to other regions. Over the 21 years, all regions showed a gradual decline in mortality rates, though the pace of reduction varied geographically. This pattern likely reflects differences in risk factor prevalence (such as smoking rates, dietary habits, and Helicobacter pylori infection), healthcare access disparities, and regional variations in early detection programs. The West's persistently elevated rates for the last decade may correlate with higher rates of obesity and processed meat consumption, while the Midwest's lower mortality could be attributed to demographic factors and earlier adoption of cancer screening protocols. The convergence of mortality trends across regions in later years suggests potential nationwide improvements in treatment modalities and public health interventions.(\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eAlthough gastric cancer mortality rates are declining across the U.S., the disease remains a significant concern. It is crucial to explore prevention and early detection strategies, similar to those implemented in countries like Japan, Korea, and China, where gastric cancer incidence is higher than in the U.S. Additionally, further research is needed to understand the underlying causes of these disparities, allowing for targeted interventions while also advancing cancer treatment strategies.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOpen Access provided by Qatar National Library\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contribution Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eS.M.I.K. and H.S. conceptualized the study and developed the study design. N.F. and M.K. contributed to the data extraction and initial analysis. M.W. and A.R. performed the statistical analysis and created the tables. M.I.S. and A.Q. reviewed and contributed to the methodology and interpretation of results. J.I. supervised the analysis and drafted the manuscript. All authors reviewed and provided critical revisions to the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding Statement:\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eThis analysis was conducted without any specific financial support or sponsorship. Open Access funding support is acknowledged from Qatar National Library.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest Disclosure:\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eThe authors declare no competing financial interests or personal relationships that could have influenced the findings or conclusions of this analysis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics Approval Statement:\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eThis CDC analysis is based solely on publicly available data and did not involve direct research with human participants or animals. Therefore, ethical approval was not required.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePatient Consent Statement:\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eThis analysis does not include direct patient involvement or identifiable personal data; patient consent was not required.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePermission to Reproduce Material from Other Sources:\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eNo copyrighted material requiring permission for reproduction was used in this analysis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to Publish declaration:\u003c/strong\u003e Not Applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to Participate declaration:\u003c/strong\u003e Not Applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTrial registration number:\u003c/strong\u003e Not Applicable\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018 Nov;68(6):394\u0026ndash;424.\u003c/li\u003e\n\u003cli\u003eNishimuni M, Claro LCL, Braghiroli MIFM. Advancements and challenges in gastric cancer: epidemiology, biomarkers, and therapeutic strategies. Surg Exp Pathol. 2024 Sep 27;7(1):19. \u003c/li\u003e\n\u003cli\u003eTan N, Wu H, Cao M, Yang F, Yan X, He S, et al. Global, regional, and national burden of early-onset gastric cancer. Cancer Biol Med. 2024 Aug 7;21(8):667\u0026ndash;78. \u003c/li\u003e\n\u003cli\u003eSiegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020 Jan;70(1):7\u0026ndash;30. \u003c/li\u003e\n\u003cli\u003eWong MCS, Huang J, Chan PSF, Choi P, Lao XQ, Chan SM, et al. Global Incidence and Mortality of Gastric Cancer, 1980-2018. JAMA Netw Open. 2021 Jul 1;4(7):e2118457. \u003c/li\u003e\n\u003cli\u003eHolowatyj AN, Ulrich CM, Lewis MA. Racial/Ethnic Patterns of Young-Onset Noncardia Gastric Cancer. Cancer Prev Res Phila Pa. 2019 Nov;12(11):771\u0026ndash;80. \u003c/li\u003e\n\u003cli\u003eLin JL, Lin JX, Lin GT, Huang CM, Zheng CH, Xie JW, et al. Global incidence and mortality trends of gastric cancer and predicted mortality of gastric cancer by 2035. BMC Public Health. 2024 Jul 2;24(1):1763. \u003c/li\u003e\n\u003cli\u003eSiegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA Cancer J Clin. 2022 Jan;72(1):7\u0026ndash;33. \u003c/li\u003e\n\u003cli\u003eMultiple Cause of Death, 1999-2020 Request [Internet]. [cited 2025 Feb 4]. Available from: https://wonder.cdc.gov/mcd-icd10.html\u003c/li\u003e\n\u003cli\u003evon Elm E, Altman DG, Egger M, Pocock SJ, G\u0026oslash;tzsche PC, Vandenbroucke JP, et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. J Clin Epidemiol. 2008 Apr;61(4):344\u0026ndash;9. \u003c/li\u003e\n\u003cli\u003eIngram DD, Franco SJ. 2013 NCHS Urban-Rural Classification Scheme for Counties. Vital Health Stat 2. 2014 Apr;(166):1\u0026ndash;73. \u003c/li\u003e\n\u003cli\u003eAnderson RN, Rosenberg HM. Age standardization of death rates: implementation of the year 2000 standard. Natl Vital Stat Rep Cent Dis Control Prev Natl Cent Health Stat Natl Vital Stat Syst. 1998 Oct 7;47(3):1\u0026ndash;16, 20. \u003c/li\u003e\n\u003cli\u003eJoinpoint Regression Program [Internet]. [cited 2025 Feb 4]. Available from: https://surveillance.cancer.gov/joinpoint/\u003c/li\u003e\n\u003cli\u003eTorres-Roman JS, Alvarez CS, Guerra-Canchari P, Valcarcel B, Martinez-Herrera JF, D\u0026aacute;vila-Hern\u0026aacute;ndez CA, et al. Sex and age differences in mortality trends of gastric cancer among Hispanic/Latino populations in the United States, Latin America, and the Caribbean. Lancet Reg Health Am. 2022 Dec;16:100376. \u003c/li\u003e\n\u003cli\u003eAxon A. Helicobacter pylori: what do we still need to know? J Clin Gastroenterol. 2006 Jan;40(1):15\u0026ndash;9. \u003c/li\u003e\n\u003cli\u003eVerdecchia A, Corazziari I, Gatta G, Lisi D, Faivre J, Forman D, et al. Explaining gastric cancer survival differences among European countries. Int J Cancer. 2004 May 1;109(5):737\u0026ndash;41. \u003c/li\u003e\n\u003cli\u003eTorres J, Correa P, Ferreccio C, Hernandez-Suarez G, Herrero R, Cavazza-Porro M, et al. Gastric cancer incidence and mortality is associated with altitude in the mountainous regions of Pacific Latin America. Cancer Causes Control CCC. 2013 Feb;24(2):249\u0026ndash;56. \u003c/li\u003e\n\u003cli\u003eThrift AP, El-Serag HB. Burden of Gastric Cancer. Clin Gastroenterol Hepatol Off Clin Pract J Am Gastroenterol Assoc. 2020 Mar;18(3):534\u0026ndash;42. \u003c/li\u003e\n\u003cli\u003eNgoan LT, Mizoue T, Fujino Y, Tokui N, Yoshimura T. Dietary factors and stomach cancer mortality. Br J Cancer. 2002 Jul 1;87(1):37\u0026ndash;42. \u003c/li\u003e\n\u003cli\u003eSong Y, Liu X, Cheng W, Li H, Zhang D. The global, regional and national burden of stomach cancer and its attributable risk factors from 1990 to 2019. Sci Rep. 2022 Jul 7;12(1):11542. \u003c/li\u003e\n\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":"Temporal trends, Gastric Cancer, USA population","lastPublishedDoi":"10.21203/rs.3.rs-6327806/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6327806/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eGastric cancer is a leading cause of mortality worldwide, with pronounced variations in outcomes across populations. This study investigates U.S. trends in age-adjusted mortality rates (AAMRs) for gastric cancer from 1999 to 2023, examining differences by sex, race, region, and urbanization to uncover critical patterns and inequities.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eData were extracted from the CDC WONDER database using ICD-10 code C16 to identify gastric cancer-related deaths in adults aged 25 and older. AAMRs per 1,000,000 population were calculated and stratified by year, sex, race/ethnicity, geographic region, and urban-rural classification. Trends were analyzed using Joinpoint regression to determine annual percentage changes (APC) and 95% confidence intervals (CI). Statistical significance was set at p\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eFrom 1999 to 2023, there were 312,300 gastric cancer deaths (185,391 men, 126,909 women). Overall, AAMRs declined consistently, with APCs of -3.4 for the period 1999 to 2007, -2.2 for 2007 to 2018, and \u0026minus;\u0026thinsp;1.2 for 2018 to 2023. Men showed a more pronounced decline, with APCs of -3.6 for 1999 to 2009 and \u0026minus;\u0026thinsp;2.2 for 2009 to 2023, compared to women, who had APCs of -3.1 for 1999 to 2008, -1.9 for 2008 to 2018, and \u0026minus;\u0026thinsp;0.8 for 2018 to 2023. Non-Hispanic Black populations experienced a decline in AAMR with an APC of -3.3 for 1999 to 2020, while Hispanic/Latino and Asian/Pacific Islander populations showed declines with APCs of -2.8 for 1999 to 2011 and \u0026minus;\u0026thinsp;3.8 for 1999 to 2020, respectively. Metropolitan areas saw AAMR reductions with APCs of -3.3 for 1999 to 2008 and \u0026minus;\u0026thinsp;2.2 for 2008 to 2020, while non-metropolitan areas had larger initial declines with an APC of -3.6 for 1999 to 2006 but slower decreases with an APC of -2.0 for 2006 to 2020. Geographically, the Northeast had the highest AAMR (62.9), followed by the West (61.7), South (57.4), and Midwest (50.9). Hawaii recorded the highest state-level AAMR (96.5), while Wyoming had the lowest (36.6). States in the top 90th percentile included Alaska, California, and New York, whereas Utah, Idaho, and Iowa were among the lowest.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eGastric cancer mortality in the U.S. has declined over the past two decades, but the pace of reduction has slowed in recent years. Significant disparities persist across sex, racial, and geographic groups, underscoring the need for targeted interventions to address these inequities and improve outcomes in vulnerable populations.\u003c/p\u003e","manuscriptTitle":"Trends in Gastric Cancer Mortality in the US: A Population-Based Analysis, 1999-2023","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-13 08:18:08","doi":"10.21203/rs.3.rs-6327806/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":"ed20600b-4190-41a6-baa2-5154608943dc","owner":[],"postedDate":"May 13th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-07-24T15:53:37+00:00","versionOfRecord":[],"versionCreatedAt":"2025-05-13 08:18:08","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6327806","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6327806","identity":"rs-6327806","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}