Trends and disparities in mortality from malignant neoplasms of digestive organs and from malignant neoplasms of digestive organs with obesity among U.S. adults aged >45 years from 1999 to 2020 using CDC WONDER data

Trends and disparities in mortality from malignant neoplasms of digestive organs and from malignant neoplasms of digestive organs with obesity among U.S. adults aged >45 years from 1999 to 2020 using CDC WONDER data | 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 and disparities in mortality from malignant neoplasms of digestive organs and from malignant neoplasms of digestive organs with obesity among U.S. adults aged >45 years from 1999 to 2020 using CDC WONDER data Baijia Tan, yihong zeng, shaojie li, Jason Widjaja This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8451314/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 7 You are reading this latest preprint version Abstract Background & Objective: Malignant neoplasms of digestive organs are a leading cause of death among U.S. adults, and obesity is a significant risk factor. Although the overall mortality rate for digestive tract cancers has declined nationally, the long-term trends and distribution disparities in obesity-related digestive tract cancer mortality across demographic subgroups remain unclear. This study aims to analyze the trends and disparities in obesity-related digestive tract cancer mortality among U.S. adults aged ≥ 45 years from 1999 to 2020. Methods Data for individuals aged ≥ 45 years with malignant neoplasms of digestive organs (ICD-10 codes: C15-C26) and with obesity (ICD-10 code: E66) listed as causes of death were extracted from the CDC WONDER database. The Joinpoint Regression Program was used to calculate the age-adjusted mortality rate (AAMR) per 100,000 population, annual percent change (APC), average annual percent change (AAPC), and corresponding 95% confidence intervals (CIs). Results Between 1999 and 2020, a total of 3,371,216 deaths from digestive tract cancers occurred among individuals aged ≥ 45 years, of which 7,303 (0.22%) were obesity-related. The overall AAMR for digestive tract cancers decreased significantly [AAPC = -1.08% (95% CI: -1.13, -1.02)]. In contrast, the AAMR for obesity-related digestive tract cancers increased significantly from 0.17 (1999) to 0.48 (2020) per 100,000 [AAPC = 4.62% (95% CI: 3.94, 5.55)]. This increasing trend was consistent across all subgroups but was particularly pronounced among males (AAPC: 5.91%), non-Hispanic Black individuals (AAPC: 4.75%), and residents of rural areas (AAPC: 5.38%). Conclusion During the study period, while the overall mortality rate for digestive tract cancers decreased among U.S. adults aged ≥ 45 years, the mortality rate for obesity-related digestive tract cancers increased sharply, with significant disparities by sex, race/ethnicity, and geography. These findings underscore the urgency of integrating obesity prevention and control as a crucial component of comprehensive strategies for malignant neoplasms of digestive organs control, particularly through targeted interventions in high-risk populations. Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 1. Introduction Malignant neoplasms of the digestive organs are among the most common cancers globally in terms of both incidence and mortality, encompassing cancers of the esophagus, stomach, colorectum, liver, pancreas, gallbladder, and other sites [ 1 ] . Digestive tract cancers constitute a significant portion of the global cancer burden, particularly in developed countries, where their development is closely linked to various lifestyle and environmental factors [ 2 ] . In the United States, although mortality rates for some malignant neoplasms of digestive organs have declined in recent years, the overall disease burden remains substantial, especially among the elderly [ 3 ] . Concurrently, obesity has become a global public health challenge. In the U.S., adult obesity prevalence has risen steadily over the past decades [ 4 ] . Obesity is not only strongly associated with cardiovascular diseases and type 2 diabetes but is also established as an independent risk factor for several cancers, including various digestive tract malignancies [ 5 ] . Obesity promotes tumor initiation and progression through multiple mechanisms such as chronic inflammation, insulin resistance, and hormonal dysregulation, significantly increasing mortality risk [ 6 ] . While studies have explored associations between obesity and specific malignant neoplasms of digestive organss (e.g., colorectal, liver cancer) [ 7 , 8 ] , research on the long-term trends and population distribution of obesity as a contributing cause of death within overall malignant neoplasms of digestive organs mortality remains limited. Furthermore, systematic nationwide studies elucidating potential disparities in obesity-related malignant neoplasms of digestive organs mortality across different genders, ages, races/ethnicities, geographic regions, and levels of urbanization are lacking [ 9 ] . Therefore, utilizing national mortality data from the U.S. Centers for Disease Control and Prevention (CDC) WONDER database for 1999–2020, this study aimed to analyze the long-term trends in mortality from digestive tract cancers and from obesity-related digestive tract cancers among U.S. adults aged ≥ 45 years. It further investigated disparities by sex, age, race/ethnicity, census region, and urbanization level. The findings are expected to provide scientific evidence for developing targeted public health interventions to reduce the burden of obesity-related digestive tract cancers [ 10 ] . 2. Methods 2.1 Data Acquisition We queried the CDC WONDER database [ 11 ] for publicly available multiple cause-of-death data. We selected data for deaths occurring from 1999 to 2020 among individuals aged ≥ 45 years where malignant neoplasms of digestive organs and obesity were listed as causes of death. Diagnoses were coded using the International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10) [ 12 ] : digestive tract cancers (ICD-10: C15-C26) and obesity (ICD-10: E66). The data included information on sex (male/female), age group (45–54, 55–64, 65–74, 75–84, 85+), race/ethnicity (Non-Hispanic White, Non-Hispanic Black, Non-Hispanic Other, Hispanic), and state of residence. Based on the 2013 U.S. Census classifications, populations were categorized into three urbanization levels: large metropolitan (population ≥ 1 million), medium/small metropolitan (population 50,000–999,999), and rural (population < 50,000). States were grouped into four census regions (Northeast, Midwest, South, West) as defined by the U.S. Census Bureau. Records with missing values were excluded. 2.2 Statistical Analysis The crude mortality rate (CMR) and age-adjusted mortality rate (AAMR) per 100,000 population were calculated. The CMR was calculated by dividing the annual number of deaths related to digestive tract cancers and obesity by the corresponding U.S. population estimate. The AAMR was standardized to the 2000 U.S. standard population to account for changes in age distribution over time. For comparing mortality trends across age groups, CMR was used. Trend analysis was performed using log-linear regression models to calculate the annual percent change (APC) and average annual percent change (AAPC) to assess significant changes in mortality over time. The Joinpoint Regression Program (Joinpoint version 5.4.0, National Cancer Institute, USA) was used to identify significant inflection points (join points) where mortality trends changed. The APC for each segment between join points was calculated with 95% confidence intervals (CI) using a Monte Carlo permutation test. Differences between groups were compared using the two-sample t-test or ANOVA. Statistical significance was set at P < 0.05. 3. Results 3.1. Overall Between 1999 and 2020, there were 3,371,216 deaths from digestive tract cancers among individuals aged ≥ 45 years. Males accounted for 56.35% (1,899,530) and females for 43.65% (1,471,686). By age group, 8.44% (284,450) were aged 45–54, 19.37% (652,847) were 55–64, 26.12% (880,681) were 65–74, 28.07% (946,282) were 75–84, and 17.80% (606,956) were ≥ 85 years. The total number of obesity-related digestive tract cancer deaths among those aged ≥ 45 years was 7,303. Males accounted for 52.43% (3,829) and females for 47.57% (3,474). By age group, 11.50% (840) were 45–54, 28.39% (2,073) were 55–64, 33.97% (2,481) were 65–74, 20.98% (1,532) were 75–84, and 5.16% (377) were ≥ 85 years. 3.2. Annual Trends Overall, the AAMR for digestive tract cancers among individuals aged ≥ 45 years was 129.300 (95% CI: 129.157–129.434) per 100,000, and for obesity-related digestive tract cancers, it was 0.286 (95% CI: 0.280–0.293). In 1999, the AAMR for digestive tract cancers was 147.83 (95% CI: 147.06–148.60), decreasing to 119.31 (95% CI: 118.74–119.87) in 2020. The overall AAMR showed a significant decreasing trend from 1999 to 2020, with an AAPC of -1.08% (95% CI: -1.13 to -1.02, P < 0.05). Specifically, a marked decline occurred from 1999 to 2009 (APC: -1.46%, 95% CI: -1.70 to -1.31, P < 0.05), followed by a slower decline from 2009 to 2020 (APC: -0.73%, 95% CI: -0.85 to -0.55, P < 0.05) (Fig. 1 A). In contrast, the AAMR for obesity-related digestive tract cancers increased from 0.17 (95% CI: 0.14–0.20) in 1999 to 0.48 (95% CI: 0.44–0.51) in 2020, with an AAPC of 4.62% (95% CI: 3.94 to 5.55, P < 0.05) (Fig. 1 B). 3.3. Stratification by Sex The AAMR for digestive tract cancers was consistently and significantly higher in males (167.387, 95% CI: 167.145–167.629) than in females (99.006, 95% CI: 98.845–99.167) (P < 0.05). The AAMR for obesity-related digestive tract cancers was also significantly higher in males (0.305, 95% CI: 0.295–0.315) than in females (0.242, 95% CI: 0.234–0.250) (P < 0.05). In 1999, the AAMR was 192.32 (95% CI: 190.92–193.71) for males and 115.53 (95% CI: 114.65–116.42) for females. By 2020, it had decreased to 154.15 (95% CI: 153.19–155.11) for males and 90.38 (95% CI: 89.71–91.04) for females. From 1999 to 2020, the AAMR for males showed a significant decreasing trend with an AAPC of -1.13% (95% CI: -1.18 to -1.06, P < 0.05): a sharp decline from 1999 to 2007 (APC: -1.58%, 95% CI: -1.95 to -1.37, P < 0.05) followed by a slower decline from 2007 to 2020 (APC: -0.85%, 95% CI: -0.94 to -0.71, P < 0.05). The AAMR for females also decreased significantly with an AAPC of -1.22% (95% CI: -1.31 to -1.14, P < 0.05): a sharp decline from 1999 to 2011 (APC: -1.63%, 95% CI: -1.91 to -1.47, P < 0.05) followed by a slower decline from 2011 to 2020 (APC: -0.68%, 95% CI: -0.91 to -0.21, P < 0.05) (Fig. 2 A). Notably, from 1999 to 2020, the AAMR for obesity-related digestive tract cancers increased significantly in both sexes. For males, it rose from 0.17 (95% CI: 0.13–0.22) in 1999 to 0.57 (95% CI: 0.51–0.62) in 2020, with an AAPC of 5.91% (95% CI: 5.00 to 7.32, P < 0.05). For females, it rose from 0.16 (95% CI: 0.12–0.20) in 1999 to 0.42 (95% CI: 0.38–0.47) in 2020, with an AAPC of 3.88% (95% CI: 2.93 to 5.18, P < 0.05) (Fig. 2 B). 3.4. Stratification by Age Participants were categorized into two age groups: 45–64 years and ≥ 65 years. The AAMR for digestive tract cancers was significantly higher in the ≥ 65 group (264.925, 95% CI: 264.951–265.259) than in the 45–64 group (52.111, 95% CI: 52.005–52.217) (P < 0.05). The AAMR for obesity-related digestive tract cancers was also significantly higher in the ≥ 65 group (0.475, 95% CI: 0.461–0.490) than in the 45–64 group (0.179, 95% CI: 0.172–0.185) (P < 0.05). For the 45–64 age group, the AAMR for digestive tract cancers decreased from 53.63 (95% CI: 53.04–54.21) in 1999 to 51.12 (95% CI: 50.65–51.59) in 2020, with an AAPC of -0.26% (95% CI: -0.34 to -0.19, P < 0.05). Specifically, there was a decreasing trend from 1999 to 2005 (APC: -0.99%, 95% CI: -1.53 to -0.64, P < 0.05), a brief increasing trend from 2005 to 2014 (APC: 0.58%, 95% CI: 0.41 to 0.89, P < 0.05), and a decreasing trend again from 2014 to 2020 (APC: -0.80%, 95% CI: -1.15 to -0.54, P < 0.05). For the ≥ 65 group, the AAMR decreased from 313.37 (95% CI: 311.51–315.24) in 1999 to 239.12 (95% CI: 237.80–240.44) in 2020, with an AAPC of -1.35% (95% CI: -1.41 to -1.29, P < 0.05). A sharp decline occurred from 1999 to 2013 (APC: -1.73%, 95% CI: -1.85 to -1.63, P < 0.05), followed by a slower decline from 2013 to 2020 (APC: -0.58%, 95% CI: -0.83 to -0.22, P < 0.05) (Fig. 3 A). In contrast, the AAMR for obesity-related digestive tract cancers showed an increasing trend in both age groups from 1999 to 2020. The AAPC was 4.79% (95% CI: 3.62 to 6.46, P < 0.05) for the 45–64 group and 4.51% (95% CI: 4.05 to 5.13, P < 0.05) for the ≥ 65 group (Fig. 3 B). 3.5. Stratification by Race/Ethnicity From 1999 to 2020, the AAMR for digestive tract cancers was highest among non-Hispanic Black or African American individuals, followed by non-Hispanic White, Hispanic or Latino, and non-Hispanic Other racial groups. For non-Hispanic Black individuals, the AAMR decreased from 207.31 (95% CI: 204.13–210.48) in 1999 to 147.62 (95% CI: 145.62–149.61) in 2020, with an AAPC of -1.65% (95% CI: -1.72 to -1.58, P < 0.05). For non-Hispanic White individuals, it decreased from 142.66 (95% CI: 141.83–143.49) to 117.72 (95% CI: 117.07–118.38), with an AAPC of -0.98% (95% CI: -1.03 to -0.92, P < 0.05). For Hispanic or Latino individuals, it decreased from 128.59 (95% CI: 125.25–131.92) to 112.12 (95% CI: 110.35–113.89), with an AAPC of -0.73% (95% CI: -0.86 to -0.61, P < 0.05). For the non-Hispanic Other group, it decreased from 132.35 (95% CI: 127.81–136.88) to 99.29 (95% CI: 97.14–101.43), with an AAPC of -1.54% (95% CI: -1.65 to -1.41, P < 0.05) (Fig. 4 A). The AAMR for obesity-related digestive tract cancers was also highest among non-Hispanic Black individuals, increasing from 0.24 (95% CI: 0.15–0.37) in 1999 to 0.63 (95% CI: 0.51–0.76) in 2020, with an AAPC of 4.75% (95% CI: 2.70 to 6.61, P < 0.05). It was followed by non-Hispanic White individuals, increasing from 0.17 (95% CI: 0.14–0.20) to 0.51 (95% CI: 0.47–0.55), with an AAPC of 5.00% (95% CI: 4.21 to 6.06, P < 0.05) (Fig. 4 B). 3.6. Stratification by Census Region Disparities in the AAMR for digestive tract cancers persisted across census regions from 1999 to 2020. In the Northeast, the AAMR decreased from 160.49 (95% CI: 158.73–162.24) to 115.84 (95% CI: 114.54–117.14), with an AAPC of -1.63% (95% CI: -1.69 to -1.55, P < 0.05). In the Midwest, it decreased from 151.09 (95% CI: 149.49–152.70) to 123.25 (95% CI: 122.00–124.49), with an AAPC of -0.99% (95% CI: -1.04 to -0.93, P < 0.05). In the South, it decreased from 142.89 (95% CI: 141.61–144.17) to 121.33 (95% CI: 120.41–122.45), with an AAPC of -0.85% (95% CI: -0.93 to -0.75, P < 0.05). In the West, it decreased from 139.14 (95% CI: 137.46–140.82) to 114.84 (95% CI: 113.67–116.00), with an AAPC of -1.00% (95% CI: -1.08 to -0.90, P < 0.05) (Fig. 5 A). The AAMR for obesity-related digestive tract cancers increased in all census regions from 1999 to 2020. In the Northeast, it increased from 0.14 (95% CI: 0.09–0.20) to 0.48 (95% CI: 0.40–0.57), with an AAPC of 4.63% (95% CI: 3.23 to 6.55, P < 0.05). In the Midwest, it increased from 0.19 (95% CI: 0.13–0.26) to 0.56 (95% CI: 0.47–0.64), with an AAPC of 4.51% (95% CI: 3.05 to 6.60, P < 0.05). In the South, it increased from 0.13 (95% CI: 0.10–0.18) to 0.49 (95% CI: 0.43–0.54), with an AAPC of 5.75% (95% CI: 4.94 to 6.88, P < 0.05). In the West, it increased from 0.16 (95% CI: 0.11–0.23) to 0.48 (95% CI: 0.41–0.55), with an AAPC of 4.09% (95% CI: 3.00 to 5.62, P < 0.05) (Fig. 5 B). 3.7. Stratification by Urbanization Level Throughout the study period, disparities in the AAMR for digestive tract cancers existed across urbanization levels. The overall AAMR was highest in rural areas (134.10, 95% CI: 133.77–134.44), followed by large metropolitan areas (129.29, 95% CI: 129.10–129.48), and then medium/small metropolitan areas (126.88, 95% CI: 126.64–127.13). Specifically, in rural areas, the AAMR decreased from 146.28 (95% CI: 144.51–148.05) in 1999 to 131.29 (95% CI: 129.82–132.77) in 2020, with an AAPC of -0.53% (95% CI: -0.56 to -0.49, P < 0.05). In large metropolitan areas, it decreased from 151.79 (95% CI: 150.68–152.89) to 115.33 (95% CI: 114.57–116.10), with an AAPC of -1.34% (95% CI: -1.38 to -1.28, P < 0.05). In medium/small metropolitan areas, it decreased from 142.37 (95% CI: 141.00–143.74) to 120.27 (95% CI: 119.26–121.29), with an AAPC of -0.91% (95% CI: -1.00 to -0.79, P < 0.05) (Fig. 6 A). Regarding obesity-related digestive tract cancers, the overall AAMR was highest in rural areas (0.38, 95% CI: 0.36–0.40), followed by medium/small metropolitan areas (0.30, 95% CI: 0.29–0.32), and then large metropolitan areas (0.22, 95% CI: 0.21–0.23). Specifically, in rural areas, the AAMR increased from 0.13 (95% CI: 0.08–0.20) in 1999 to 0.72 (95% CI: 0.61–0.83) in 2020, with an AAPC of 5.38% (95% CI: 4.34 to 6.83, P < 0.05). In medium/small metropolitan areas, it increased from 0.17 (95% CI: 0.13–0.23) to 0.56 (95% CI: 0.49–0.63), with an AAPC of 6.05% (95% CI: 5.14 to 7.29, P < 0.05). In large metropolitan areas, it increased from 0.15 (95% CI: 0.11–0.19) to 0.44 (95% CI: 0.39–0.49), with an AAPC of 4.58% (95% CI: 3.39 to 6.32, P < 0.05) (Fig. 6 B). 4. Discussion This study, based on nationwide mortality data from the U.S. CDC WONDER database (1999–2020), systematically analyzed the long-term trends and population disparities in mortality from digestive tract cancers and from obesity-related digestive tract cancers among adults aged ≥ 45 years. The key public health finding is that while the overall mortality rate for digestive tract cancers showed a significant declining trend, the mortality rate for obesity-related digestive tract cancers increased sharply over the 22-year period, with pronounced disparities by sex, race/ethnicity, geographic region, and urbanization level. These results address a gap in the literature regarding long-term trends and population distribution of obesity in relation to overall malignant neoplasms of digestive organs mortality, providing critical evidence for optimizing cancer control strategies. Our findings show that the AAMR for digestive tract cancers among U.S. adults aged ≥ 45 years declined at an average annual rate of 1.08% from 1999 to 2020, with the rate of decline slowing after 2009 (APC changing from − 1.46% to -0.73%). This trend aligns with overall progress in U.S. cancer control [ 3 ] . Contributing factors likely include: 1) Increased screening for malignant neoplasms of digestive organss, particularly improved colorectal cancer screening via colonoscopy, leading to early detection and intervention [ 13 , 14 ] ; 2) Advances in treatment, such as targeted therapies and immunotherapy for cancers like colorectal and pancreatic cancer, improving prognosis for advanced-stage patients [ 15 , 16 ] ; 3) Effective control of traditional risk factors like smoking and excessive alcohol consumption, indirectly reducing incidence and mortality for related cancers (e.g., esophageal, stomach) [ 17 , 18 ] . The slowing decline post-2009 may be associated with an aging population [ 19 ] and the counteracting effect of certain risk factors (e.g., obesity) [ 20 ] , suggesting diminishing marginal returns from traditional control measures and the need for new intervention targets. In stark contrast, the AAMR for obesity-related digestive tract cancers increased from 0.17 per 100,000 in 1999 [ 4 ] to 0.48 per 100,000 in 2020, with an average annual growth rate of 4.62% and no apparent inflection point. This phenomenon can be explained by two core drivers: First, the continuous rise in U.S. adult obesity prevalence provides a "fertile ground" for cancer development—according to CDC data, U.S. adult obesity prevalence reached 41.9% in 2020, nearly double that of 1999. Second, obesity promotes malignant neoplasms of digestive organs initiation and progression through multiple pathways, including chronic low-grade inflammation (adipose tissue secretion of pro-inflammatory cytokines like IL-6 and TNF-α inducing cell malignancy) [ 21 , 22 ] , insulin resistance and hyperinsulinemia (activation of the insulin-like growth factor-1 (IGF-1) pathway promoting tumor cell proliferation and angiogenesis) [ 23 ] , and hormonal dysregulation (e.g., elevated estrogen levels associated with increased colorectal and liver cancer risk) [ 24 ] . Furthermore, obesity may reduce treatment response rates and increase recurrence risk for malignant neoplasms of digestive organss, thereby elevating mortality probability, which could also contribute to the rising mortality trend [ 25 , 26 ] . The study found that males had significantly higher AAMRs for both overall and obesity-related digestive tract cancers than females, and the annual growth rate for obesity-related cancers (AAPC = 5.91%) far exceeded that for females (AAPC = 3.88%). This disparity may stem from sex-related physiological and behavioral heterogeneity: 1) A higher prevalence of abdominal obesity among obese males, which is more strongly linked to insulin resistance and inflammation, causing more significant damage to the digestive mucosa [ 27 , 28 ] ; 2) Male dietary patterns (e.g., higher red and processed meat intake), combined with higher rates of alcohol consumption and smoking, may synergize with obesity to further amplify cancer risk [ 29 , 30 ] ; 3) Hormonal differences, where male androgen levels might enhance obesity-related cancer risk by modulating metabolic pathways, while female estrogen may offer some protective effect against certain malignant neoplasms of digestive organss (e.g., colorectal cancer) [ 31 , 32 ] . Non-Hispanic Black individuals consistently had the highest AAMR for overall digestive tract cancers, but the rate of decline (AAPC=-1.65%) was faster than for non-Hispanic White individuals (AAPC=-0.98%) [ 33 ] . However, non-Hispanic Black individuals also had the highest AAMR for obesity-related malignant neoplasms of digestive organss, with a sharp acceleration in growth rate after 2018 (APC = 27.18%). This reflects persistent racial health inequities in the U.S.: 1) The obesity prevalence among non-Hispanic Black adults (49.6%) is significantly higher than other groups, often accompanied by comorbidities like hypertension and diabetes, further increasing cancer risk [ 34 , 35 ] ; 2) Lower healthcare access, including lower rates of malignant neoplasms of digestive organs screening and guideline-concordant treatment among non-Hispanic Black individuals, leading to worse outcomes for obesity-related cancer patients [ 36 , 37 ] ; 3) Lower socioeconomic status, associated with dietary patterns high in energy-dense, nutrient-poor foods and limited opportunities for physical activity, hindering effective weight control [ 38 , 39 ] . Notably, the annual growth rate for obesity-related cancers among non-Hispanic White individuals (AAPC = 5.00%) was slightly higher than for non-Hispanic Black individuals (AAPC = 4.75%), suggesting a rapidly accumulating risk in the White population alongside the general rise in obesity prevalence [ 40 ] . Geographically, the South had the highest annual growth rate for obesity-related malignant neoplasms of digestive organss (AAPC = 5.75%), consistent with the region's high obesity prevalence and unhealthy dietary patterns (e.g., high intake of fried foods and sugary beverages) [ 41 ] . Regarding urbanization, rural areas had a significantly higher AAMR for obesity-related cancers (0.38 per 100,000) than large metropolitan areas (0.22 per 100,000), with an annual growth rate of 5.38%. Medium/small metropolitan areas had the fastest growth rate (AAPC = 6.05%). This disparity is primarily rooted in inequitable public health resources: 1) Weaker health awareness, insufficient dissemination of obesity prevention knowledge, and lower participation in weight management behaviors in rural areas [ 42 ] ; 2) Disadvantaged food environments, with limited access to fresh fruits and vegetables and higher availability of processed foods and fast food in rural areas, contributing to high obesity rates [ 43 , 44 ] ; 3) Scarce healthcare resources, including lower screening coverage for malignant neoplasms of digestive organss and suboptimal management of obesity-related comorbidities (e.g., diabetes, fatty liver disease), indirectly promoting cancer progression [ 45 , 46 ] ; 4) Lack of exercise facilities and safe spaces for physical activity in rural areas, leading to generally lower activity levels. Additionally, the sharp increase in the obesity-related cancer growth rate in large metropolitan areas after 2018 (APC = 20.66%) might be related to rapid lifestyle changes associated with urbanization (e.g., sedentary behavior, proliferation of food delivery services), indicating new challenges for obesity-related cancer control even in well-resourced areas. 5. Limitations This study has several limitations that should be acknowledged: 1) The data are based on ICD codes from death certificates, which may be subject to classification bias. Some obesity-related malignant neoplasms of digestive organs deaths might be missed if obesity was not recorded as a cause of death, or coding errors might exist. 2) Lack of individual-level information, such as Body Mass Index (BMI) category, waist circumference, lifestyle factors (diet, physical activity), socioeconomic status, and comorbidities, precluding further analysis of their moderating effects on mortality trends. 3) The analysis did not distinguish between specific sites of digestive tract cancer (e.g., colorectal, liver, pancreatic). The impact of obesity likely varies by cancer site, making it difficult to reveal risk profiles for specific cancer types. 4) As an ecological study, it cannot establish causality between obesity and malignant neoplasms of digestive organs mortality, only reflecting population-level association trends. 6. Conclusion This analysis of the U.S. CDC WONDER database from 1999 to 2020 systematically reveals a duality in mortality trends for malignant neoplasms of the digestive organs among adults aged ≥ 45 years: a continued decline in overall mortality contrasted with a sharp increase in obesity-related mortality. This core finding underscores the growing severity of obesity as a key risk factor for digestive tract cancers, with its impact unevenly distributed across demographic subgroups. Specifically, the rapid rise in obesity-related malignant neoplasms of digestive organs mortality (AAPC: 4.62%) coincides with the concurrent upward trend in U.S. adult obesity prevalence, suggesting that the obesity epidemic is a major contextual driver. This increasing trend is particularly pronounced among males, non-Hispanic Black individuals, and residents of rural areas, reflecting disparities in health risks across gender, racial, and socioeconomic dimensions. These differences are likely linked to varying exposures to compound risk factors (e.g., unhealthy diet, physical inactivity), disparities in healthcare access, and gaps in the management of chronic conditions. Despite overall progress in screening, diagnosis, and treatment for malignant neoplasms of digestive organss, this study indicates that obesity—a modifiable risk factor—is partially offsetting the benefits of these public health achievements and poses a new, significant challenge. Therefore, integrating obesity prevention and control into the core of national comprehensive cancer control strategies is an urgent priority. Declarations Conflict of interest The authors declare no competing interests. Ethics approval Not applicable for a CDC wonder analysis article. 9. Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Author Contribution All authors contributed to this study. 7. 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Ann Surg Oncol 2020,27(6):1724–5. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 04 Feb, 2026 Reviewers agreed at journal 02 Feb, 2026 Reviewers invited by journal 21 Jan, 2026 Editor invited by journal 30 Dec, 2025 Editor assigned by journal 29 Dec, 2025 Submission checks completed at journal 29 Dec, 2025 First submitted to journal 25 Dec, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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1","display":"","copyAsset":false,"role":"figure","size":945197,"visible":true,"origin":"","legend":"\u003cp\u003e(A) Overall malignant neoplasms of digestive organs AAMRs per 1,000,000 in the United States, 1999 to 2020.\u003c/p\u003e\n\u003cp\u003e(B) Overall malignant neoplasms of digestive organs with obesity related AAMRs per 1,000,000 in the United States, 1999 to 2020.\u003c/p\u003e","description":"","filename":"image1.png","url":"https://assets-eu.researchsquare.com/files/rs-8451314/v1/2d196bb222729ff29dd487da.png"},{"id":100925519,"identity":"508e1fb7-80ef-4df0-96e2-c78d4608ec73","added_by":"auto","created_at":"2026-01-22 22:09:29","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1379034,"visible":true,"origin":"","legend":"\u003cp\u003e(A) Sex-stratified malignant neoplasms of digestive organs AAMRs per 1,000,000 in the United States, 1999 to 2020.\u003c/p\u003e\n\u003cp\u003e(B) Sex-stratified malignant neoplasms of digestive organswith obesity related AAMRs per 1,000,000 in the United States, 1999 to 2020.\u003c/p\u003e","description":"","filename":"image2.png","url":"https://assets-eu.researchsquare.com/files/rs-8451314/v1/a9e66e1e3fbcbd7f1b8164d6.png"},{"id":100950568,"identity":"64b00d76-ea72-442f-a01e-1393f270f920","added_by":"auto","created_at":"2026-01-23 07:08:37","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":1430045,"visible":true,"origin":"","legend":"\u003cp\u003e(A) Age-stratified malignant neoplasms of digestive organsAAMRs per 1,000,000 in the United States, 1999 to 2020.\u003c/p\u003e\n\u003cp\u003e(B) Age-stratified malignant neoplasms of digestive organswith obesity related AAMRs per 1,000,000 in the United States, 1999 to 2020.\u003c/p\u003e","description":"","filename":"image3.png","url":"https://assets-eu.researchsquare.com/files/rs-8451314/v1/cc1e86fdacd2b04334a0ef81.png"},{"id":100925541,"identity":"2a68f3ad-8c1e-418c-9b9f-46c523733ed3","added_by":"auto","created_at":"2026-01-22 22:09:31","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":1499823,"visible":true,"origin":"","legend":"\u003cp\u003e(A) Race-stratified malignant neoplasms of digestive organsAAMRs per 1,000,000 in the United States, 1999 to 2020.\u003c/p\u003e\n\u003cp\u003e(B) Race-stratified malignant neoplasms of digestive organswith obesity related AAMRs per 1,000,000 in the United States, 1999 to 2020.\u003c/p\u003e","description":"","filename":"image4.png","url":"https://assets-eu.researchsquare.com/files/rs-8451314/v1/ca2966d41d68d7c8660414d9.png"},{"id":100925532,"identity":"e185d119-28c3-427f-b519-056e221e48f2","added_by":"auto","created_at":"2026-01-22 22:09:29","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":1651843,"visible":true,"origin":"","legend":"\u003cp\u003e(A) Malignant neoplasms of digestive organs related AAMRs per 1,000,000 stratified by census regions in the United States, 1999 to 2020.\u003c/p\u003e\n\u003cp\u003e(B) Malignant neoplasms of digestive organs with obesity related AAMRs per 1,000,000 stratified by census regions in the United States, 1999 to 2020.\u003c/p\u003e","description":"","filename":"image5.png","url":"https://assets-eu.researchsquare.com/files/rs-8451314/v1/ff4b5818631baefec4df2cae.png"},{"id":100951728,"identity":"5dc1469a-92ea-4094-8316-32773393cf7c","added_by":"auto","created_at":"2026-01-23 07:11:09","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":1497138,"visible":true,"origin":"","legend":"\u003cp\u003e(A) Malignant neoplasms of digestive organs related AAMRs per 1,000,000 stratified by urbanization in the United States, 1999 to 2020.\u003c/p\u003e\n\u003cp\u003e(B) Malignant neoplasms of digestive organs with obesity related AAMRs per 1,000,000 stratified by urbanization in the United States, 1999 to 2020.\u003c/p\u003e","description":"","filename":"image6.png","url":"https://assets-eu.researchsquare.com/files/rs-8451314/v1/694a0a8132931ad831d2638b.png"},{"id":101296587,"identity":"52a625d8-e223-4356-ba93-5b950b3f8c0e","added_by":"auto","created_at":"2026-01-28 09:16:29","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":8066225,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8451314/v1/dd9033c1-c662-49d2-a15c-c0c1fbeeb93b.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Trends and disparities in mortality from malignant neoplasms of digestive organs and from malignant neoplasms of digestive organs with obesity among U.S. adults aged \u003e45 years from 1999 to 2020 using CDC WONDER data","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eMalignant neoplasms of the digestive organs are among the most common cancers globally in terms of both incidence and mortality, encompassing cancers of the esophagus, stomach, colorectum, liver, pancreas, gallbladder, and other sites\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e. Digestive tract cancers constitute a significant portion of the global cancer burden, particularly in developed countries, where their development is closely linked to various lifestyle and environmental factors\u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e. In the United States, although mortality rates for some malignant neoplasms of digestive organs have declined in recent years, the overall disease burden remains substantial, especially among the elderly\u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eConcurrently, obesity has become a global public health challenge. In the U.S., adult obesity prevalence has risen steadily over the past decades\u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e. Obesity is not only strongly associated with cardiovascular diseases and type 2 diabetes but is also established as an independent risk factor for several cancers, including various digestive tract malignancies\u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e. Obesity promotes tumor initiation and progression through multiple mechanisms such as chronic inflammation, insulin resistance, and hormonal dysregulation, significantly increasing mortality risk\u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eWhile studies have explored associations between obesity and specific malignant neoplasms of digestive organss (e.g., colorectal, liver cancer)\u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e, research on the long-term trends and population distribution of obesity as a contributing cause of death within overall malignant neoplasms of digestive organs mortality remains limited. Furthermore, systematic nationwide studies elucidating potential disparities in obesity-related malignant neoplasms of digestive organs mortality across different genders, ages, races/ethnicities, geographic regions, and levels of urbanization are lacking\u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eTherefore, utilizing national mortality data from the U.S. Centers for Disease Control and Prevention (CDC) WONDER database for 1999\u0026ndash;2020, this study aimed to analyze the long-term trends in mortality from digestive tract cancers and from obesity-related digestive tract cancers among U.S. adults aged\u0026thinsp;\u0026ge;\u0026thinsp;45 years. It further investigated disparities by sex, age, race/ethnicity, census region, and urbanization level. The findings are expected to provide scientific evidence for developing targeted public health interventions to reduce the burden of obesity-related digestive tract cancers\u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e"},{"header":"2. Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Data Acquisition\u003c/h2\u003e \u003cp\u003eWe queried the CDC WONDER database\u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e for publicly available multiple cause-of-death data. We selected data for deaths occurring from 1999 to 2020 among individuals aged\u0026thinsp;\u0026ge;\u0026thinsp;45 years where malignant neoplasms of digestive organs and obesity were listed as causes of death. Diagnoses were coded using the International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10)\u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e: digestive tract cancers (ICD-10: C15-C26) and obesity (ICD-10: E66). The data included information on sex (male/female), age group (45\u0026ndash;54, 55\u0026ndash;64, 65\u0026ndash;74, 75\u0026ndash;84, 85+), race/ethnicity (Non-Hispanic White, Non-Hispanic Black, Non-Hispanic Other, Hispanic), and state of residence. Based on the 2013 U.S. Census classifications, populations were categorized into three urbanization levels: large metropolitan (population\u0026thinsp;\u0026ge;\u0026thinsp;1\u0026nbsp;million), medium/small metropolitan (population 50,000\u0026ndash;999,999), and rural (population\u0026thinsp;\u0026lt;\u0026thinsp;50,000). States were grouped into four census regions (Northeast, Midwest, South, West) as defined by the U.S. Census Bureau. Records with missing values were excluded.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Statistical Analysis\u003c/h2\u003e \u003cp\u003eThe crude mortality rate (CMR) and age-adjusted mortality rate (AAMR) per 100,000 population were calculated. The CMR was calculated by dividing the annual number of deaths related to digestive tract cancers and obesity by the corresponding U.S. population estimate. The AAMR was standardized to the 2000 U.S. standard population to account for changes in age distribution over time. For comparing mortality trends across age groups, CMR was used. Trend analysis was performed using log-linear regression models to calculate the annual percent change (APC) and average annual percent change (AAPC) to assess significant changes in mortality over time. The Joinpoint Regression Program (Joinpoint version 5.4.0, National Cancer Institute, USA) was used to identify significant inflection points (join points) where mortality trends changed. The APC for each segment between join points was calculated with 95% confidence intervals (CI) using a Monte Carlo permutation test. Differences between groups were compared using the two-sample t-test or ANOVA. Statistical significance was set at P\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results","content":"\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e3.1. Overall\u003c/h2\u003e \u003cp\u003eBetween 1999 and 2020, there were 3,371,216 deaths from digestive tract cancers among individuals aged\u0026thinsp;\u0026ge;\u0026thinsp;45 years. Males accounted for 56.35% (1,899,530) and females for 43.65% (1,471,686). By age group, 8.44% (284,450) were aged 45\u0026ndash;54, 19.37% (652,847) were 55\u0026ndash;64, 26.12% (880,681) were 65\u0026ndash;74, 28.07% (946,282) were 75\u0026ndash;84, and 17.80% (606,956) were \u0026ge;\u0026thinsp;85 years. The total number of obesity-related digestive tract cancer deaths among those aged\u0026thinsp;\u0026ge;\u0026thinsp;45 years was 7,303. Males accounted for 52.43% (3,829) and females for 47.57% (3,474). By age group, 11.50% (840) were 45\u0026ndash;54, 28.39% (2,073) were 55\u0026ndash;64, 33.97% (2,481) were 65\u0026ndash;74, 20.98% (1,532) were 75\u0026ndash;84, and 5.16% (377) were \u0026ge;\u0026thinsp;85 years.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e3.2. Annual Trends\u003c/h2\u003e \u003cp\u003eOverall, the AAMR for digestive tract cancers among individuals aged\u0026thinsp;\u0026ge;\u0026thinsp;45 years was 129.300 (95% CI: 129.157\u0026ndash;129.434) per 100,000, and for obesity-related digestive tract cancers, it was 0.286 (95% CI: 0.280\u0026ndash;0.293). In 1999, the AAMR for digestive tract cancers was 147.83 (95% CI: 147.06\u0026ndash;148.60), decreasing to 119.31 (95% CI: 118.74\u0026ndash;119.87) in 2020. The overall AAMR showed a significant decreasing trend from 1999 to 2020, with an AAPC of -1.08% (95% CI: -1.13 to -1.02, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Specifically, a marked decline occurred from 1999 to 2009 (APC: -1.46%, 95% CI: -1.70 to -1.31, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05), followed by a slower decline from 2009 to 2020 (APC: -0.73%, 95% CI: -0.85 to -0.55, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA). In contrast, the AAMR for obesity-related digestive tract cancers increased from 0.17 (95% CI: 0.14\u0026ndash;0.20) in 1999 to 0.48 (95% CI: 0.44\u0026ndash;0.51) in 2020, with an AAPC of 4.62% (95% CI: 3.94 to 5.55, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e3.3. Stratification by Sex\u003c/h2\u003e \u003cp\u003eThe AAMR for digestive tract cancers was consistently and significantly higher in males (167.387, 95% CI: 167.145\u0026ndash;167.629) than in females (99.006, 95% CI: 98.845\u0026ndash;99.167) (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). The AAMR for obesity-related digestive tract cancers was also significantly higher in males (0.305, 95% CI: 0.295\u0026ndash;0.315) than in females (0.242, 95% CI: 0.234\u0026ndash;0.250) (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e \u003cp\u003eIn 1999, the AAMR was 192.32 (95% CI: 190.92\u0026ndash;193.71) for males and 115.53 (95% CI: 114.65\u0026ndash;116.42) for females. By 2020, it had decreased to 154.15 (95% CI: 153.19\u0026ndash;155.11) for males and 90.38 (95% CI: 89.71\u0026ndash;91.04) for females. From 1999 to 2020, the AAMR for males showed a significant decreasing trend with an AAPC of -1.13% (95% CI: -1.18 to -1.06, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05): a sharp decline from 1999 to 2007 (APC: -1.58%, 95% CI: -1.95 to -1.37, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05) followed by a slower decline from 2007 to 2020 (APC: -0.85%, 95% CI: -0.94 to -0.71, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). The AAMR for females also decreased significantly with an AAPC of -1.22% (95% CI: -1.31 to -1.14, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05): a sharp decline from 1999 to 2011 (APC: -1.63%, 95% CI: -1.91 to -1.47, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05) followed by a slower decline from 2011 to 2020 (APC: -0.68%, 95% CI: -0.91 to -0.21, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eNotably, from 1999 to 2020, the AAMR for obesity-related digestive tract cancers increased significantly in both sexes. For males, it rose from 0.17 (95% CI: 0.13\u0026ndash;0.22) in 1999 to 0.57 (95% CI: 0.51\u0026ndash;0.62) in 2020, with an AAPC of 5.91% (95% CI: 5.00 to 7.32, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). For females, it rose from 0.16 (95% CI: 0.12\u0026ndash;0.20) in 1999 to 0.42 (95% CI: 0.38\u0026ndash;0.47) in 2020, with an AAPC of 3.88% (95% CI: 2.93 to 5.18, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e3.4. Stratification by Age\u003c/h2\u003e \u003cp\u003eParticipants were categorized into two age groups: 45\u0026ndash;64 years and \u0026ge;\u0026thinsp;65 years. The AAMR for digestive tract cancers was significantly higher in the \u0026ge;\u0026thinsp;65 group (264.925, 95% CI: 264.951\u0026ndash;265.259) than in the 45\u0026ndash;64 group (52.111, 95% CI: 52.005\u0026ndash;52.217) (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). The AAMR for obesity-related digestive tract cancers was also significantly higher in the \u0026ge;\u0026thinsp;65 group (0.475, 95% CI: 0.461\u0026ndash;0.490) than in the 45\u0026ndash;64 group (0.179, 95% CI: 0.172\u0026ndash;0.185) (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e \u003cp\u003eFor the 45\u0026ndash;64 age group, the AAMR for digestive tract cancers decreased from 53.63 (95% CI: 53.04\u0026ndash;54.21) in 1999 to 51.12 (95% CI: 50.65\u0026ndash;51.59) in 2020, with an AAPC of -0.26% (95% CI: -0.34 to -0.19, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Specifically, there was a decreasing trend from 1999 to 2005 (APC: -0.99%, 95% CI: -1.53 to -0.64, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05), a brief increasing trend from 2005 to 2014 (APC: 0.58%, 95% CI: 0.41 to 0.89, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05), and a decreasing trend again from 2014 to 2020 (APC: -0.80%, 95% CI: -1.15 to -0.54, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). For the \u0026ge;\u0026thinsp;65 group, the AAMR decreased from 313.37 (95% CI: 311.51\u0026ndash;315.24) in 1999 to 239.12 (95% CI: 237.80\u0026ndash;240.44) in 2020, with an AAPC of -1.35% (95% CI: -1.41 to -1.29, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). A sharp decline occurred from 1999 to 2013 (APC: -1.73%, 95% CI: -1.85 to -1.63, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05), followed by a slower decline from 2013 to 2020 (APC: -0.58%, 95% CI: -0.83 to -0.22, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eA).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eIn contrast, the AAMR for obesity-related digestive tract cancers showed an increasing trend in both age groups from 1999 to 2020. The AAPC was 4.79% (95% CI: 3.62 to 6.46, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05) for the 45\u0026ndash;64 group and 4.51% (95% CI: 4.05 to 5.13, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05) for the \u0026ge;\u0026thinsp;65 group (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eB).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003e3.5. Stratification by Race/Ethnicity\u003c/h2\u003e \u003cp\u003eFrom 1999 to 2020, the AAMR for digestive tract cancers was highest among non-Hispanic Black or African American individuals, followed by non-Hispanic White, Hispanic or Latino, and non-Hispanic Other racial groups. For non-Hispanic Black individuals, the AAMR decreased from 207.31 (95% CI: 204.13\u0026ndash;210.48) in 1999 to 147.62 (95% CI: 145.62\u0026ndash;149.61) in 2020, with an AAPC of -1.65% (95% CI: -1.72 to -1.58, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). For non-Hispanic White individuals, it decreased from 142.66 (95% CI: 141.83\u0026ndash;143.49) to 117.72 (95% CI: 117.07\u0026ndash;118.38), with an AAPC of -0.98% (95% CI: -1.03 to -0.92, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). For Hispanic or Latino individuals, it decreased from 128.59 (95% CI: 125.25\u0026ndash;131.92) to 112.12 (95% CI: 110.35\u0026ndash;113.89), with an AAPC of -0.73% (95% CI: -0.86 to -0.61, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). For the non-Hispanic Other group, it decreased from 132.35 (95% CI: 127.81\u0026ndash;136.88) to 99.29 (95% CI: 97.14\u0026ndash;101.43), with an AAPC of -1.54% (95% CI: -1.65 to -1.41, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05) (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eA).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe AAMR for obesity-related digestive tract cancers was also highest among non-Hispanic Black individuals, increasing from 0.24 (95% CI: 0.15\u0026ndash;0.37) in 1999 to 0.63 (95% CI: 0.51\u0026ndash;0.76) in 2020, with an AAPC of 4.75% (95% CI: 2.70 to 6.61, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). It was followed by non-Hispanic White individuals, increasing from 0.17 (95% CI: 0.14\u0026ndash;0.20) to 0.51 (95% CI: 0.47\u0026ndash;0.55), with an AAPC of 5.00% (95% CI: 4.21 to 6.06, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05) (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eB).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003e3.6. Stratification by Census Region\u003c/h2\u003e \u003cp\u003eDisparities in the AAMR for digestive tract cancers persisted across census regions from 1999 to 2020. In the Northeast, the AAMR decreased from 160.49 (95% CI: 158.73\u0026ndash;162.24) to 115.84 (95% CI: 114.54\u0026ndash;117.14), with an AAPC of -1.63% (95% CI: -1.69 to -1.55, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). In the Midwest, it decreased from 151.09 (95% CI: 149.49\u0026ndash;152.70) to 123.25 (95% CI: 122.00\u0026ndash;124.49), with an AAPC of -0.99% (95% CI: -1.04 to -0.93, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). In the South, it decreased from 142.89 (95% CI: 141.61\u0026ndash;144.17) to 121.33 (95% CI: 120.41\u0026ndash;122.45), with an AAPC of -0.85% (95% CI: -0.93 to -0.75, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). In the West, it decreased from 139.14 (95% CI: 137.46\u0026ndash;140.82) to 114.84 (95% CI: 113.67\u0026ndash;116.00), with an AAPC of -1.00% (95% CI: -1.08 to -0.90, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05) (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eA).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe AAMR for obesity-related digestive tract cancers increased in all census regions from 1999 to 2020. In the Northeast, it increased from 0.14 (95% CI: 0.09\u0026ndash;0.20) to 0.48 (95% CI: 0.40\u0026ndash;0.57), with an AAPC of 4.63% (95% CI: 3.23 to 6.55, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). In the Midwest, it increased from 0.19 (95% CI: 0.13\u0026ndash;0.26) to 0.56 (95% CI: 0.47\u0026ndash;0.64), with an AAPC of 4.51% (95% CI: 3.05 to 6.60, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). In the South, it increased from 0.13 (95% CI: 0.10\u0026ndash;0.18) to 0.49 (95% CI: 0.43\u0026ndash;0.54), with an AAPC of 5.75% (95% CI: 4.94 to 6.88, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). In the West, it increased from 0.16 (95% CI: 0.11\u0026ndash;0.23) to 0.48 (95% CI: 0.41\u0026ndash;0.55), with an AAPC of 4.09% (95% CI: 3.00 to 5.62, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05) (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eB).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003e3.7. Stratification by Urbanization Level\u003c/h2\u003e \u003cp\u003eThroughout the study period, disparities in the AAMR for digestive tract cancers existed across urbanization levels. The overall AAMR was highest in rural areas (134.10, 95% CI: 133.77\u0026ndash;134.44), followed by large metropolitan areas (129.29, 95% CI: 129.10\u0026ndash;129.48), and then medium/small metropolitan areas (126.88, 95% CI: 126.64\u0026ndash;127.13). Specifically, in rural areas, the AAMR decreased from 146.28 (95% CI: 144.51\u0026ndash;148.05) in 1999 to 131.29 (95% CI: 129.82\u0026ndash;132.77) in 2020, with an AAPC of -0.53% (95% CI: -0.56 to -0.49, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). In large metropolitan areas, it decreased from 151.79 (95% CI: 150.68\u0026ndash;152.89) to 115.33 (95% CI: 114.57\u0026ndash;116.10), with an AAPC of -1.34% (95% CI: -1.38 to -1.28, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). In medium/small metropolitan areas, it decreased from 142.37 (95% CI: 141.00\u0026ndash;143.74) to 120.27 (95% CI: 119.26\u0026ndash;121.29), with an AAPC of -0.91% (95% CI: -1.00 to -0.79, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05) (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003eA).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eRegarding obesity-related digestive tract cancers, the overall AAMR was highest in rural areas (0.38, 95% CI: 0.36\u0026ndash;0.40), followed by medium/small metropolitan areas (0.30, 95% CI: 0.29\u0026ndash;0.32), and then large metropolitan areas (0.22, 95% CI: 0.21\u0026ndash;0.23). Specifically, in rural areas, the AAMR increased from 0.13 (95% CI: 0.08\u0026ndash;0.20) in 1999 to 0.72 (95% CI: 0.61\u0026ndash;0.83) in 2020, with an AAPC of 5.38% (95% CI: 4.34 to 6.83, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). In medium/small metropolitan areas, it increased from 0.17 (95% CI: 0.13\u0026ndash;0.23) to 0.56 (95% CI: 0.49\u0026ndash;0.63), with an AAPC of 6.05% (95% CI: 5.14 to 7.29, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). In large metropolitan areas, it increased from 0.15 (95% CI: 0.11\u0026ndash;0.19) to 0.44 (95% CI: 0.39\u0026ndash;0.49), with an AAPC of 4.58% (95% CI: 3.39 to 6.32, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05) (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003eB).\u003c/p\u003e \u003c/div\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eThis study, based on nationwide mortality data from the U.S. CDC WONDER database (1999\u0026ndash;2020), systematically analyzed the long-term trends and population disparities in mortality from digestive tract cancers and from obesity-related digestive tract cancers among adults aged\u0026thinsp;\u0026ge;\u0026thinsp;45 years. The key public health finding is that while the overall mortality rate for digestive tract cancers showed a significant declining trend, the mortality rate for obesity-related digestive tract cancers increased sharply over the 22-year period, with pronounced disparities by sex, race/ethnicity, geographic region, and urbanization level. These results address a gap in the literature regarding long-term trends and population distribution of obesity in relation to overall malignant neoplasms of digestive organs mortality, providing critical evidence for optimizing cancer control strategies.\u003c/p\u003e \u003cp\u003eOur findings show that the AAMR for digestive tract cancers among U.S. adults aged\u0026thinsp;\u0026ge;\u0026thinsp;45 years declined at an average annual rate of 1.08% from 1999 to 2020, with the rate of decline slowing after 2009 (APC changing from \u0026minus;\u0026thinsp;1.46% to -0.73%). This trend aligns with overall progress in U.S. cancer control\u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e. Contributing factors likely include: 1) Increased screening for malignant neoplasms of digestive organss, particularly improved colorectal cancer screening via colonoscopy, leading to early detection and intervention\u003csup\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e; 2) Advances in treatment, such as targeted therapies and immunotherapy for cancers like colorectal and pancreatic cancer, improving prognosis for advanced-stage patients\u003csup\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/sup\u003e; 3) Effective control of traditional risk factors like smoking and excessive alcohol consumption, indirectly reducing incidence and mortality for related cancers (e.g., esophageal, stomach)\u003csup\u003e[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/sup\u003e. The slowing decline post-2009 may be associated with an aging population\u003csup\u003e[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/sup\u003e and the counteracting effect of certain risk factors (e.g., obesity)\u003csup\u003e[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e, suggesting diminishing marginal returns from traditional control measures and the need for new intervention targets.\u003c/p\u003e \u003cp\u003eIn stark contrast, the AAMR for obesity-related digestive tract cancers increased from 0.17 per 100,000 in 1999\u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e to 0.48 per 100,000 in 2020, with an average annual growth rate of 4.62% and no apparent inflection point. This phenomenon can be explained by two core drivers: First, the continuous rise in U.S. adult obesity prevalence provides a \"fertile ground\" for cancer development\u0026mdash;according to CDC data, U.S. adult obesity prevalence reached 41.9% in 2020, nearly double that of 1999. Second, obesity promotes malignant neoplasms of digestive organs initiation and progression through multiple pathways, including chronic low-grade inflammation (adipose tissue secretion of pro-inflammatory cytokines like IL-6 and TNF-α inducing cell malignancy)\u003csup\u003e[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/sup\u003e, insulin resistance and hyperinsulinemia (activation of the insulin-like growth factor-1 (IGF-1) pathway promoting tumor cell proliferation and angiogenesis)\u003csup\u003e[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/sup\u003e, and hormonal dysregulation (e.g., elevated estrogen levels associated with increased colorectal and liver cancer risk)\u003csup\u003e[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/sup\u003e. Furthermore, obesity may reduce treatment response rates and increase recurrence risk for malignant neoplasms of digestive organss, thereby elevating mortality probability, which could also contribute to the rising mortality trend\u003csup\u003e[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe study found that males had significantly higher AAMRs for both overall and obesity-related digestive tract cancers than females, and the annual growth rate for obesity-related cancers (AAPC\u0026thinsp;=\u0026thinsp;5.91%) far exceeded that for females (AAPC\u0026thinsp;=\u0026thinsp;3.88%). This disparity may stem from sex-related physiological and behavioral heterogeneity: 1) A higher prevalence of abdominal obesity among obese males, which is more strongly linked to insulin resistance and inflammation, causing more significant damage to the digestive mucosa\u003csup\u003e[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]\u003c/sup\u003e; 2) Male dietary patterns (e.g., higher red and processed meat intake), combined with higher rates of alcohol consumption and smoking, may synergize with obesity to further amplify cancer risk\u003csup\u003e[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]\u003c/sup\u003e; 3) Hormonal differences, where male androgen levels might enhance obesity-related cancer risk by modulating metabolic pathways, while female estrogen may offer some protective effect against certain malignant neoplasms of digestive organss (e.g., colorectal cancer)\u003csup\u003e[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eNon-Hispanic Black individuals consistently had the highest AAMR for overall digestive tract cancers, but the rate of decline (AAPC=-1.65%) was faster than for non-Hispanic White individuals (AAPC=-0.98%)\u003csup\u003e[\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]\u003c/sup\u003e. However, non-Hispanic Black individuals also had the highest AAMR for obesity-related malignant neoplasms of digestive organss, with a sharp acceleration in growth rate after 2018 (APC\u0026thinsp;=\u0026thinsp;27.18%). This reflects persistent racial health inequities in the U.S.: 1) The obesity prevalence among non-Hispanic Black adults (49.6%) is significantly higher than other groups, often accompanied by comorbidities like hypertension and diabetes, further increasing cancer risk\u003csup\u003e[\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]\u003c/sup\u003e; 2) Lower healthcare access, including lower rates of malignant neoplasms of digestive organs screening and guideline-concordant treatment among non-Hispanic Black individuals, leading to worse outcomes for obesity-related cancer patients\u003csup\u003e[\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e, \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]\u003c/sup\u003e; 3) Lower socioeconomic status, associated with dietary patterns high in energy-dense, nutrient-poor foods and limited opportunities for physical activity, hindering effective weight control\u003csup\u003e[\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e, \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]\u003c/sup\u003e. Notably, the annual growth rate for obesity-related cancers among non-Hispanic White individuals (AAPC\u0026thinsp;=\u0026thinsp;5.00%) was slightly higher than for non-Hispanic Black individuals (AAPC\u0026thinsp;=\u0026thinsp;4.75%), suggesting a rapidly accumulating risk in the White population alongside the general rise in obesity prevalence\u003csup\u003e[\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eGeographically, the South had the highest annual growth rate for obesity-related malignant neoplasms of digestive organss (AAPC\u0026thinsp;=\u0026thinsp;5.75%), consistent with the region's high obesity prevalence and unhealthy dietary patterns (e.g., high intake of fried foods and sugary beverages)\u003csup\u003e[\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]\u003c/sup\u003e. Regarding urbanization, rural areas had a significantly higher AAMR for obesity-related cancers (0.38 per 100,000) than large metropolitan areas (0.22 per 100,000), with an annual growth rate of 5.38%. Medium/small metropolitan areas had the fastest growth rate (AAPC\u0026thinsp;=\u0026thinsp;6.05%). This disparity is primarily rooted in inequitable public health resources: 1) Weaker health awareness, insufficient dissemination of obesity prevention knowledge, and lower participation in weight management behaviors in rural areas\u003csup\u003e[\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]\u003c/sup\u003e; 2) Disadvantaged food environments, with limited access to fresh fruits and vegetables and higher availability of processed foods and fast food in rural areas, contributing to high obesity rates\u003csup\u003e[\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e, \u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e]\u003c/sup\u003e; 3) Scarce healthcare resources, including lower screening coverage for malignant neoplasms of digestive organss and suboptimal management of obesity-related comorbidities (e.g., diabetes, fatty liver disease), indirectly promoting cancer progression\u003csup\u003e[\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e, \u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e]\u003c/sup\u003e; 4) Lack of exercise facilities and safe spaces for physical activity in rural areas, leading to generally lower activity levels. Additionally, the sharp increase in the obesity-related cancer growth rate in large metropolitan areas after 2018 (APC\u0026thinsp;=\u0026thinsp;20.66%) might be related to rapid lifestyle changes associated with urbanization (e.g., sedentary behavior, proliferation of food delivery services), indicating new challenges for obesity-related cancer control even in well-resourced areas.\u003c/p\u003e"},{"header":"5. Limitations","content":"\u003cp\u003eThis study has several limitations that should be acknowledged: 1) The data are based on ICD codes from death certificates, which may be subject to classification bias. Some obesity-related malignant neoplasms of digestive organs deaths might be missed if obesity was not recorded as a cause of death, or coding errors might exist. 2) Lack of individual-level information, such as Body Mass Index (BMI) category, waist circumference, lifestyle factors (diet, physical activity), socioeconomic status, and comorbidities, precluding further analysis of their moderating effects on mortality trends. 3) The analysis did not distinguish between specific sites of digestive tract cancer (e.g., colorectal, liver, pancreatic). The impact of obesity likely varies by cancer site, making it difficult to reveal risk profiles for specific cancer types. 4) As an ecological study, it cannot establish causality between obesity and malignant neoplasms of digestive organs mortality, only reflecting population-level association trends.\u003c/p\u003e"},{"header":"6. Conclusion","content":"\u003cp\u003eThis analysis of the U.S. CDC WONDER database from 1999 to 2020 systematically reveals a duality in mortality trends for malignant neoplasms of the digestive organs among adults aged\u0026thinsp;\u0026ge;\u0026thinsp;45 years: a continued decline in overall mortality contrasted with a sharp increase in obesity-related mortality. This core finding underscores the growing severity of obesity as a key risk factor for digestive tract cancers, with its impact unevenly distributed across demographic subgroups.\u003c/p\u003e \u003cp\u003eSpecifically, the rapid rise in obesity-related malignant neoplasms of digestive organs mortality (AAPC: 4.62%) coincides with the concurrent upward trend in U.S. adult obesity prevalence, suggesting that the obesity epidemic is a major contextual driver. This increasing trend is particularly pronounced among males, non-Hispanic Black individuals, and residents of rural areas, reflecting disparities in health risks across gender, racial, and socioeconomic dimensions. These differences are likely linked to varying exposures to compound risk factors (e.g., unhealthy diet, physical inactivity), disparities in healthcare access, and gaps in the management of chronic conditions.\u003c/p\u003e \u003cp\u003eDespite overall progress in screening, diagnosis, and treatment for malignant neoplasms of digestive organss, this study indicates that obesity\u0026mdash;a modifiable risk factor\u0026mdash;is partially offsetting the benefits of these public health achievements and poses a new, significant challenge. Therefore, integrating obesity prevention and control into the core of national comprehensive cancer control strategies is an urgent priority.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003cstrong\u003eConflict of interest\u003c/strong\u003e \u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eEthics approval\u003c/strong\u003e \u003cp\u003eNot applicable for a CDC wonder analysis article.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003e9. Funding\u003c/h2\u003e \u003cp\u003eThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eAll authors contributed to this study.\u003c/p\u003e\u003ch2\u003e7. Acknowledgements\u003c/h2\u003e \u003cp\u003eThe authors acknowledge using the CDC WONDER database to provide the data utilized in this study.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe data supporting the findings of this study are available within the article.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eSung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries[J]. CA Cancer J Clin. 2021;71(3):209\u0026ndash;49.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eArnold M, Abnet CC, Neale RE et al. Global Burden of 5 Major Types of Gastrointestinal Cancer[J]. Gastroenterology,2020,159(1):335\u0026ndash;49.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSiegel RL, Kratzer TB, Giaquinto AN, et al. Cancer statistics, 2025[J]. 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Ann Surg Oncol 2020,27(6):1724\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"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":"bmc-gastroenterology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmge","sideBox":"Learn more about [BMC Gastroenterology](http://bmcgastroenterol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmge/default.aspx","title":"BMC Gastroenterology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-8451314/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8451314/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground \u0026amp; Objective:\u003c/h2\u003e \u003cp\u003eMalignant neoplasms of digestive organs are a leading cause of death among U.S. adults, and obesity is a significant risk factor. Although the overall mortality rate for digestive tract cancers has declined nationally, the long-term trends and distribution disparities in obesity-related digestive tract cancer mortality across demographic subgroups remain unclear. This study aims to analyze the trends and disparities in obesity-related digestive tract cancer mortality among U.S. adults aged\u0026thinsp;\u0026ge;\u0026thinsp;45 years from 1999 to 2020.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eData for individuals aged\u0026thinsp;\u0026ge;\u0026thinsp;45 years with malignant neoplasms of digestive organs (ICD-10 codes: C15-C26) and with obesity (ICD-10 code: E66) listed as causes of death were extracted from the CDC WONDER database. The Joinpoint Regression Program was used to calculate the age-adjusted mortality rate (AAMR) per 100,000 population, annual percent change (APC), average annual percent change (AAPC), and corresponding 95% confidence intervals (CIs).\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eBetween 1999 and 2020, a total of 3,371,216 deaths from digestive tract cancers occurred among individuals aged\u0026thinsp;\u0026ge;\u0026thinsp;45 years, of which 7,303 (0.22%) were obesity-related. The overall AAMR for digestive tract cancers decreased significantly [AAPC = -1.08% (95% CI: -1.13, -1.02)]. In contrast, the AAMR for obesity-related digestive tract cancers increased significantly from 0.17 (1999) to 0.48 (2020) per 100,000 [AAPC\u0026thinsp;=\u0026thinsp;4.62% (95% CI: 3.94, 5.55)]. This increasing trend was consistent across all subgroups but was particularly pronounced among males (AAPC: 5.91%), non-Hispanic Black individuals (AAPC: 4.75%), and residents of rural areas (AAPC: 5.38%).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eDuring the study period, while the overall mortality rate for digestive tract cancers decreased among U.S. adults aged\u0026thinsp;\u0026ge;\u0026thinsp;45 years, the mortality rate for obesity-related digestive tract cancers increased sharply, with significant disparities by sex, race/ethnicity, and geography. These findings underscore the urgency of integrating obesity prevention and control as a crucial component of comprehensive strategies for malignant neoplasms of digestive organs control, particularly through targeted interventions in high-risk populations.\u003c/p\u003e","manuscriptTitle":"Trends and disparities in mortality from malignant neoplasms of digestive organs and from malignant neoplasms of digestive organs with obesity among U.S. adults aged \u0026gt;45 years from 1999 to 2020 using CDC WONDER data","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-22 22:09:22","doi":"10.21203/rs.3.rs-8451314/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-02-04T19:07:43+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"216938107459544267188933811278466281759","date":"2026-02-02T07:24:29+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-01-21T05:17:57+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-12-30T15:48:40+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-12-29T07:10:59+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-12-29T07:10:03+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Gastroenterology","date":"2025-12-26T01:01:07+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-gastroenterology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmge","sideBox":"Learn more about [BMC Gastroenterology](http://bmcgastroenterol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmge/default.aspx","title":"BMC Gastroenterology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"ac68505d-a8a8-4de7-bfa5-72a0f690fb19","owner":[],"postedDate":"January 22nd, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-01-22T22:09:22+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-22 22:09:22","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8451314","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8451314","identity":"rs-8451314","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}