Evolving landscape of geriatric colorectal cancer: Global and regional burden, risk factor dynamics, and future scenarios (the Global Burden of Disease 1990–2040)

Evolving landscape of geriatric colorectal cancer: Global and regional burden, risk factor dynamics, and future scenarios (the Global Burden of Disease 1990–2040) | 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 Evolving landscape of geriatric colorectal cancer: Global and regional burden, risk factor dynamics, and future scenarios (the Global Burden of Disease 1990–2040) Yuwei Huo, Shengde Wu This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7297355/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 Geriatric patients diagnosed with colorectal cancer (GCRC) face elevated rates of mortality and complications; however, yet current guidelines lack randomized controlled trial (RCT) data specifically for individuals aged 75 and above (75+). Although the burden of colorectal cancer in the global population aged 65 and older has decreased, the trends in 75+ colorectal cancer patients have not been studied. This study assessed the prevalence, incidence, mortality, and Disability-Adjusted Life Years (DALYs) of geriatric colorectal cancer at global and national levels from 1990 to 2021, and projects trajectories to 2045. Using data from the 2021 Global Burden of Disease (GBD) study, we calculated age-standardized rates (ASRs) for 204 countries/regions. Joinpoint regression identified time trends through Average Annual Percentage Changes (AAPCs), while Bayesian Age-Period-Cohort models (BAPC) predicted future burdens. Globally, the burden of colorectal cancer in the population aged 75+ has decreased (AAPC of ASDR: −14.832, 95% UI: −15.179 to -14.485). However, the prevalence has significantly increased, with an average annual increase of 4.491 (95% UI: 4.347-4.635), and a much larger increase in males compared to females (9.313 [95% UI: 9.101-9.526] vs. 0.564 [95% UI: 0.380-0.748]). Major risk factors include a diet lacking whole grains, insufficient milk intake, high red meat consumption, and lack of physical exercise, which are the main causes of mortality and DALYs. Predictions indicate that by 2040, the prevalence of GCRC will increase globally, especially among males (with an expected increase of 44% in prevalence from 1990 to 2040). The burden of disease in the geriatric population aged 75+ is expected to continue to rise, with significant gender differences. Public health efforts should focus on changing dietary structures and increasing physical exercise. This study emphasizes the urgent need for intervention strategies targeting geriatric patients to address the evolving epidemiological challenges in colorectal cancer prevention and control. 75+year-old cohort Colorectal cancer Global Burden of Disease Prevalence Incidence Mortality Disability-adjusted life years Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 1. Introduction According to the latest statistics data from the International Agency for Research on Cancer, colorectal cancer (CRC) was the third most prevalent malignancy globally and the second leading cause of cancer-related mortality in 2022 [ 1 ] . The incidence of colorectal cancer increases with age, with approximately 88% of cases occurring in individuals over 50 years old [ 2 ] . Despite the significant progress has been achieved in screening for colorectal cancer in recent decades [ 3 ] , the number of geriatric individuals diagnosed with colorectal cancer increasing year by year owing to the increasing global life expectancy and the rising proportion of the geriatric population [ 4 ] . According to estimates provided by the International Agency for Research on Cancer of the World Health Organization, it is estimated that there will be 1.9 million new cases and 904,000 deaths in 2022. Furthermore, there is a significant global disparity in the burden of CRC, with the incidence in completed transition countries being 3 to 4 times higher than in transitioning countries. The highest incidence rates are found in Europe, Australia and North America. Conversely, Africa, South Asia, and Central Asia have relatively lower incidence rates [ 1 ] . Another study shows that due to socioeconomic inequalities, the mortality rate of colorectal cancer patients in poverty rural areas is 1.2 to 1.6 times higher than in other regions [ 5 ] . The large number of patients presents a significant global health challenge. The heterogeneity of geriatric patients is significant. On one hand, geriatric patients in optimal physical and mental condition may miss opportunities for radical treatment due to overly conservative treatment plans; on the other hand, frail patients may face serious complications when receiving intensive treatment [ 6 ] . This clinical decision-making dilemma as a result of the lack of large-scale cohort studies targeting geriatric patients, leading to a lack of high-quality evidence to support treatment standards [ 7 ] . For example, adjuvant chemotherapy or surgical plans developed based on data from younger patients may not be applicable to geriatric patients with complex comorbidities. Additionally, existing data often focus on traditional endpoint indicators such as survival rates, with inadequate consideration to the disease-associated burden on patients, including quality of life and functional recovery [ 8 ] , resulting in a lack of research on the disease burden of colorectal cancer patients over 75 years old. The Global Burden of Disease (GBD) database, created and managed by the Institute for Health Metrics and Evaluation (IHME), aims to provide detailed global information on diseases, injuries, and risk factors [ 9 ] , offering a unique opportunity. We present the global trends in age standerdized rate of disability-adjusted life years (DALYs), deaths, prevalence and incidence from GCRC between 1990 and 2021 using GBD2021 data and provide forecasts for the burden of GCRC up to 2040. We also conducted decomposition analysis and risk factor analysis to examine the main driving factors behind the changes in GCRC burden, as well as an analysis of health inequalities to determine the relationship between SDI and GCRC burden. This provides a basis for developing geriatric-friendly screening guidelines and stratified treatment strategies. 2. Materials and Methods Data Source The data utilized in this research was obtained from the GBD 2021 database through the Global Health Data Exchange (GHDx) query tool ( https://vizhub.healthdata.org/ gbd-results/), which provides data on the burden of 371 diseases and injuries in 21 GBD regions and 204 countries and territories between 1990 and 2021, including CRC [ 9 ] . The methodologies employed in GBD 2021 have been detailed in previously published articles [ 9 ] . This study complied with the Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER) [ 10 ] . Ethics approval was not required for this study due to the analysis of anonymized and publicly available data. Definition of Geriatric Colorectal Cancer (GCRC) In this study, colorectal cancer (CRC) was identified using ICD-11 codes C18–21, D01.0–D01.2, and D12–D12.9, encompassing both colon and rectal cancer. In accordance with previous studies, Geriatric Colorectal Cancer (GCRC) was defined as diagnoses or prevalences occurring aged 75 years and above [ 11 – 15 ] . In this study, we designated the terms “colon and rectum cancer” as the “cause”, while “incidence”, “deaths”,“prevalence”and “DALYs” were identified as the “measures”. And we collected in 5 age groups ("75–79 years","80–84 years","85–89 years","90–94 years","95 + years"). All data analyses for this investigation were finalized on April 1, 2025. Analyses were stratified by sex, socio-demographic index (SDI), and 21 GBD-defined regions (which were 21 groups of countries/territories that were geographically proximate and epidemiologically similar), such as High-Income North America, Southeast Asia, and Western Sub-Saharan Africa. Estimation of incidence, deaths, prevalence and DALYs The estimates of incidence, deaths, prevalence and disability-adjusted life years (DALYs) for GCRC were derived from the Global Burden of Disease (GBD) 2021 dataset. DALYs were calculated as the sum of years of life lost (YLLs) and years lived with disability (YLDs), with one DALY representing the loss of one year of healthy life. All rates (incidence, prevalence, mortality, and DALYs) were expressed per 100,000 individuals. To account for variations in population age structures across regions and countries—which could distort crude rate comparisons—we employed age-standardized rates (ASRs) using the world standard population from GBD 2021 as the reference [ 16 ] . Specifically, we calculated age-standardized incidence (ASIR), mortality (ASMR), prevalence (ASPR) and DALY (ASDR) rates (per 100,000 population) via this formula: where ai is the age-specific rate in the ith age group, wi is the weight in the same age subgroup of the chosen reference standard population (in which i denotes the ith age class), and A is the total number of age groups [ 17 ] .This approach minimized confounding by age disparities, enabling more accurate cross-regional assessments of the GCRC burden. Risk factors We obtained risk factors data from the GBD 2021 database, which mainly includes three categories: environment/occupational risks, behavioral risks, and metabolic risks. According to previous literature’s evidence, we selected 11 risk factors that have contribution to DALYs and deaths, including 6 dietary related factors(Diet low in whole grains, Diet low in fiber, Diet low in milk, Diet low in calcium, Diet high in red meat, Diet high in processed meat), 3 behavioral related factors(High alcohol use, Smoking, Low physical activity) and 2 metabolic related factors(High fasting plasma glucose, High body-mass index). The contribution percentage of these risk factors to DALYs and mortality will be analyzed visually. Statistical analysis We used the "segment" package in R for joinpoint analysis to assess the average annual percentage change (AAPC) trends of GCRC's ASIR, ASMR, ASPR, and ASDR burden from 1990 to 2021, with the 95% confidence intervals (CIs) for AAPC derived from linear regression models. The specific calculation methods have been described in previous studies [ 18 ] . When both AAPC and its 95% CI are > 0 (or < 0), the result is considered statistically significant, indicating an upward (or downward) trend, while if AAPC or its 95% CI includes 0, the change is deemed statistically insignificant, indicating a stable trend. To understand the contributions of aging, population growth, and epidemiological changes to the variations in incidence, prevalence, mortality, and DALY rates, this study conducted a decomposition analysis to reveal the impacts of these three factors on disease burden changes across different SDI regions. SDI is a composite indicator measuring the level of social development, ranging from 0 to 1, indicating from least developed to most developed. All countries were classified into five categories according to the SDI: Low SDI: SDI 0.85 [ 19 ] . To further assess the impact of socioeconomic levels on disease burden, we used slope index of inequality (SII) and concentration index (CI) to evaluate the absolute and relative inequalities in DALY rates.Slope index of inequality was calculated by regression of the country-level DALYs due to GCRC within populations aged 75+, utilizing a scale that reflects relative positioning based on sociodemographic development, defined by the midpoint of the cumulative class range of the population ranked by the Socio-Demographic Index (SDI). The concentration index of health inequality was calculated by fitting a Lorenz concentration curve to the observed cumulative relative distribution of populations ranked by SDI alongside the disease-related DALYs, and involved numerically integrating the area beneath the curve [ 20 ] . The 95% CI was calculated using the "Boot" package in R language. A larger slope index of inequality indicates that high SDI regions bear a greater disease burden, and vice versa [ 21 ] . The range of the concentration index is from − 1 to 1, where negative values indicate that the disease burden is more prevalent among lower socioeconomic groups, and vice versa [ 22 ] . The Bayesian age-period-cohort (BAPC) model was used to project the burden of GCRC to 2040. We used the "BAPC" and "INLA" packages in R to predict the incidence, mortality, prevalence, and DALY rates of GCRC from 2022 to 2040. The BAPC model is a commonly used method for understanding disease trend changes, based on the classical age-period-cohort model, especially in studies involving age-structured population data and complex cohort effects [ 23 ] .All statistical analyses and visualization were finished using R software (version 4.5.0). 3. Results 3.1. Disease Burden Due to Geriatric Colorectal Cancer by Regions and Countries From 1990 to 2021, the number of cases of GCRC significantly increased, nearly tripling from 1,024,219 (95% UI: 938,349 to 1,103,818) in 1990 to 2,919,947 (95% UI: 2,602,420 to 3,137,886) in 2021, as detailed in Table 1 . The ASIR rose from 244.78 (95% UI: 217.78 to 258.85) per 100,000 to 274.11 (95% UI: 210.71 to 269.75) per 100,000, indicating only a slight increase in incidence (AAPC: 0.090 [95% CI: 0.048 to 0.133], p < 0.001)(Table 1 ). The number of deaths from colorectal cancer was 207,829 (95% UI: 187,252 to 218,367) in 1990, corresponding to an ASMR of 191.71 (95% UI: 170.69 to 203.03) per 100,000; by 2021, the number of deaths from the disease rose to 443,460 (95% UI: 385,191 to 479,790), with the corresponding ASMR decreasing to 156.70 (95% UI: 133.78 to 171.06) per 100,000, indicating a significant downward trend (AAPC: -1.113 [95% CI: -1.138 to -1.089], p < 0.001)(Supplementary Table 1, Fig. 1 ). Over the same period, the ASPR increased from 873.28 (95% UI: 783.73 to 960.16) to 1010.94 (95% UI: 884.13 to 1,095.40) (AAPC: 4.491 [95% CI: 4.347 to 4.635], p < 0.001). The ASDR exhibited a significant downward trend, decreasing from 2,462.35 (95% UI: 2,218.50 to 2,602.57) per 100,000 to 2,000.51 (95% UI: 1,731.58 to 2,177.48) per 100,000 (AAPC: -14.832 [95% CI: -15.179 to -14.485], p < 0.001)(Supplementary Table 1, Fig. 1 ). In 2021, around 2,919,947 (95% UI: 2,602,420 to 3,137,886) colorectal cancer patients worldwide accounted for 5,728,257 (95% UI: 5,038,383 to 6,201,686) DALYs. In terms of gender, in 1990, the global male ASPR rate (957.14 per 100,000 population) was higher than that of females (820.97 per 100,000 population). By 2021, this trend continued, with the male ASPR rising to 1243.06 per 100,000 population, while the female ASRP remained stable, with only a slight increase to 840.72 per 100,000 population(Table 1 , Fig. 1 A). The global male ASIR rate (276.5 per 100,000 population) was higher than that of females (225.1 per 100,000 population). By 2021, the male ASIR continued to rise to 308.78 per 100,000 population, while the female ASIR decreased to 202.88 per 100,000 population(Table 1 , Fig. 1 B). During this period, the ASDR decreased for both genders, with the male ASDR dropping from 2814.1 per 100,000 to 2487.3 per 100,000 (AAPC: -10.573 [95% CI: -11.232 to -9.913], P < 0.001), and the female ASDR decreasing from 2243.7 per 100,000 to 1650.6 per 100,000 (AAPC: -19.099 [95% CI: -19.430 to -18.768], P < 0.001)(Fig. 1 C). Between 1990 and 2021, the number of deaths attributed to GCRC among males increased from 89,009 to 220,890, with the ASMR showing a downward trend, decreasing from 217.12 to 193.50 per 100,000 population (AAPC: -0.715 [95% CI: -0.759 to -0.672], P < 0.001). For females, the number rose from 118,820 to 222,570, and the ASMR showed a more pronounced downward trend compared to males: decreasing from 176.31 to 131.13 per 100,000 population (AAPC: -1.433 [95% CI: -1.469 to -1.397], P < 0.001)(Table 1 , Fig. 1 D). Males accounted for approximately 42.8% of the deaths in 1990, and by 2021, this proportion gradually increased to 49.8%. 3.2 Burden of colorectal cancer in regions Among the 5 SDI regions, the highest ASPR, ASIR, ASMR, and ASDR were observed in the high-SDI region. From 1990 to 2021, ASPR showed an increasing trend across all SDI regions, while ASMR and ASDR exhibited a decreasing trend in the high-SDI and high-middle SDI regions, with the most significant decrease trend was noted in the former region, while the remaining SDI regions showed an increasing trend. ASIR increased in all SDI regions except for the high-SDI region. Among the 21 regions, the highest ASPR was in Australasia(2,301.63/100,000[95% UI: 1,914.34 to 2,664.97]), closely followed by High-income Asia Pacific (2,243.00/100,000 [95% UI: 1,853.27 to 2,533.56]). Western Europe had the highest cases amoung all regions, with 818,023 cases (95% UI: 717,449 to 887,045), accounting for approximately 28.01% (1/4) of the global cases(Table 1 ). The highest ASMR was founded in Central Europe (267.79/100,000 [95% UI: 239.44 to 289.60]), followed by Southern Latin America (224.58/100,000 [95%UI:185.60 to 261.10]) and Western Europe(213.72/100,000 [95% UI: 176.86 to 236.08]). The highest ASIR was in Australasia (442.00/100,000[95% UI: 359.34 to 520.69]),followed by Western Europe (392.74/100,000 [95% UI: 330.44 to 432.33]). The greatest incidence number of GCRC patients was founded in East Asia (175,842 [95%UI:144,279 to 203,627]), closely followed by Western Europe (174,264 [95%UI:146,380 to 191,164]). In 2021, the highest ASDR was in Central Europe (3,499.61/100,000[95% UI: 3,154.45 to 3,777.20]), followed by Southern Latin America (2,863.06/100,000[95% UI: 2,381.49 to 3,326.31]), while the highest DALYs was in East Asia(1,444,133 [95%UI:1,194,325 to 1,689,659]), followed by Western Europe(1,226,711 [95%UI:1,026,464 to 1,348,462])(Table 1 ). 3.3 Country burden of GCRC In 2021, the GCRC prevalence count and ASPR recorded in China, Japan, and the United States were the highest(Supplementary Table 2). China reported 612,442 cases (95% UI 509,330 to 709,364) with an ASPR of 3,966.58 per 100,000 (3,310.82 to 4,594.06). Japan followed with 434,854 cases (362,207 to 478,819) with ASPR of 3,141.68 per 100,000 (2,362.74 to 3,985.97), while the United States recorded 366,053 cases (320,593 to 394,333) with ASPR of 3,088.49 per 100,000 (2,446.85 to 3,889.14). Gambia had the lowest ASPR (56.37/100,000 [95% UI: 41.98 to 74.23]). These three nations—China, Japan, and the United States—recorded the highest total numbers of incident cases of GCRC as well, with respective counts of 168,546 (137,582 to 196,316), 87,720 (69,624 to 98,554), and 72,602 (60,132 to 79,110)(Supplementary Table 3). In terms of ASIR, Netherlands led with 707.21 (573.19 to 833.05), followed by Monaco at 674.79 (495.51 to 889.99), and Bermuda at 659.84 (514.26 to 840.91). Papua New Guinea exhibited the lowest ASIR at 29.57 per 100,000 (95% UI: 20.99 to 40.08). Regarding DALYs, China reported the highest number of cases with 1,374,963 (1,121,844 to 1,623,509), Japan with 550,362 (437,544 to 614,325), and the United States with 453,047 (382,069 to 493,830)(Supplementary Table 4). Conversely, Monaco had the highest ASDR at 4,709.98 (3,477.97 to 6,088.76), followed by Uruguay at 4,593.30 (3,797.01 to 5,399.79) and Croatia at 4,155.30 (3,411.49 to 4,983.01). Bangladesh reported the lowest ASDR at 432.48 per 100,000 (95% UI: 302.46 to 617.79). The first three countries for deaths in terms of ASMR were the same: China with 101,647 deaths (83,034 to 118,761) and an ASMR of 362.72 (298.30 to 429.53), Japan with 46,058 deaths (35,684 to 51,842) and an ASMR of 362.16 (264.00 to 472.89), and the United States with 35,143 deaths (28,959 to 38,553) and an ASMR of 319.51 (261.64 to 383.75). Papua New Guinea had the lowest ASDR at 34.43 per 100,000 (95% UI: 24.48 to 46.81)(Supplementary Table 5). During the period from 1990 to 2021, among 204 countries and regions, 192 countries showed an increasing trend in ASPR, with 30 countries/regions having prevalence cases that doubled or more(Supplementary Table 2, Fig. 2 A). The greatest increase countries were Bermuda (AAPC: 46.86 [95% CI: 43.59 to 50.13]), Republic of Korea (AAPC: 45.03 [95% CI: 43.57 to 46.49]), and Monaco (AAPC: 37.9 [95% CI: 36.84 to 38.96]). The GCRC ASIR increased in 172 countries and regions (Fig. 2 B), with the significant increase of ASIR was observed in Republic of Korea, rising from 171.07 per 100,000 people (95% UI: 135.22 to 210.68) to 395.87 per 100,000 people (95% UI: 290.43 to 515.58), with an AAPC of 7.11 (95% CI: 6.64 to 7.58). While the greatest declines were observed in San Marino (AAPC: -8.41 [95% CI: -9.46 to -7.37]), Austria (AAPC: -4.84 [95% CI: -5.02 to -2.97]), and the United States of America (AAPC: -4.24 [95% CI: -4.44 to -4.04])(Supplementary Table 3). The ASDR of GCRC in 133 countries and territories showed escalating trend (Supplementary Table 4 Fig. 2 C), with Romania experiencing the fastest growth, increasing from 1,374.01 per 100,000 people (95% UI: 1,150.27 to 1,624.26) to 2,933.52 per 100,000 people (95% UI: 2,433.71 to 3,518.88), with an AAPC of 51.41 (95% CI: 48.45 to 54.37). Meanwhile, 71 countries showed a downward trend. San Marino had the fastest decline (AAPC: -82.91 [95% CI: -90.31 to -75.51]), followed by Greenland (AAPC: -71.22 [95% CI: -75.80 to -66.64]) and Germany (AAPC: -66.41 [95% CI: -70.89 to -61.94]). In 71 countries/regions, ASMR showed a decreasing trend(Supplementary Table 5, Fig. 2 D). The greatest declines in ASMR were observed in San Marino (AAPC: -6.89 [95% CI: -7.45 to -6.33]), Germany (AAPC: -5.44 [95% CI: -5.69 to -5.18]), and Greenland (AAPC: -5.21 [95% CI: -5.60 to -4.83]). Meanwhile, Romania showed the greatest increase, from 103.70 (86.10-122.87) per 100,000 to 215.55(178.60-259.16) per 100,000, with an AAPC of 3.66 (95% CI 3.45 to 3.88). 3.4 Decomposition analysis of GCRC Figure 3 shows the impact of population growth, aging, and epidemiological changes on GCRC changes. From 1990 to 2021, the changes in prevalence among the GCRC population were primarily due to population growth. This was more pronounced in high SDI regions as well as low SDI regions, while in middle SDI and high-middle SDI regions, it was influenced by epidemiological changes as well. Notably, while epidemiological changes contributed to the increase in incidence and prevalence, they played a mitigating role in mortality and DALYs rates. 3.5. Health inequalities of GCRC The inequality slope index of DALY rate is positive, indicating that as the SDI increases, the burden borne by GCRC becomes heavier. From 1990 to 2021, the inequality slope decreased from 3143.82 to 2108.51, indicating that the absolute level of inequality is shrinking(Fig. 4 ). The concentration index in ASDR is negative, indicating that both low and high SDI countries bear a greater burden of GCRC. In 2021, the concentration index decreased(Fig. 4 ), the relative level of inequality is shrinking. Figure 5 shows the burden of 11 risk factors on GCRC disease mortality and DALY in 21 GBD regions in 2021. Dietary deficiencies in whole grains(deaths: 17.9%, DALYs: 17.9%), lack of milk(deaths: 14.9%, DALYs: 14.8%), high intake of red meat(deaths: 14.7%, DALYs: 14.8%), and lack of physical exercise(deaths: 9.8%, DALYs: 9.5%) are the main causes of mortality and DALY, while obesity(deaths: 8.8%, DALYs: 8.9%), low calcium intake(deaths: 8.2%, DALYs: 8.2%), high consumption of processed meats(deaths: 5.7%, DALYs: 5.7%), high fasting plasma glucose(deaths: 8.9%, DALYs: 8.9%), low dietary fiber intake(deaths: 1.4%, DALYs: 1.3%), as well as smoking(deaths: 3.1%, DALYs: 3.3%) and drinking(deaths: 4.4%, DALYs: 4.5%) had less contribution to deaths and DALYs. The lack of whole grain nutrition is a common risk across all regions. The impact of different risk factors on mortality and DALY in geriatric patients varies by region, with the main risk factors in high SDI countries including lack of exercise, obesity, and excessive consumption of processed meats, while in low SDI countries, the primary causes are due to lack of milk and calcium. 3.6.Prediction of disease burden of EOCRC from 2022 to 2040 According to the BAPC model prediction, it is expected that from 2022 to 2040, the ASPR will continue to rise. By 2040, the global ASPR is projected to escalate to 1087.4698 [95%CI: 405.7223, 1769.2172](Fig. 6 A), while ASDR, ASMR, and ASIR show a downward trend, decreasing to (240.3985 [95%CI: 98.03321, 382.7638])(Fig. 6 B), (1663.487 [95%CI: 709.2769, 2617.698])(Fig. 6 C) and (128.2597 [95%CI: 58.39403, 198.1253])(Fig. 6 D) by 2040, with gender differences further widening. It is noteworthy that men still bear a heavier GCRC burden, with the ASPR for men rising more significantly in the future (1379.0179 [95%CI: 472.8397, 2285.1960]) compared to women (865.5796 [95%CI: 317.7059, 1413.4533])(Fig. 6 A). 4. Discussion Based on the 2021 GBD database, this study explores the burden and trends of global, regional, and national GCRC (75+) from 1990 to 2021. Over the past 32 years, the number of geriatric individuals suffering from diseases, incidence, mortality, and total DALYs has shown a significant increase globally. Specifically, the number of global GCRC cases has nearly tripled since 1990, accompanied by a notable rise in ASPR, especially among the male population. Through decomposition analysis, we found that population growth is the primary reason for the increase in current cases, followed by changes in epidemiology. Although an increase in both death counts and DALYs, reaching 2.13 fold and 2.02 fold of the original values respectively, the ASMR and ASDR for both sexes show a steady decline. From 1990 to 2021, contrary to the rising trend of EOCRC incidence reported in the literature [ 23 ] , the ASIR trend for geriatric patients remains stable, with female GCRC declining globally. However, the ASIR in males showed an overall upward trend and remained higher than in females. In regions with medium-high and high SDI, ASMR, ASIR, and ASDR show a declining trend, while in low, low-middle, and middle SDI regions, these indicators have been increasing year by year. This association may be attributed to enhanced public health awareness, widespread adoption of early screening programs, improved healthcare standards and optimized health insurance systems in middle-high and high SDI regions [ 24 , 25 ] . It is expected that by 2040, both male and female ASPR will rise, indicating that the burden of geriatric colorectal cancer will gradually increase in the future, which is of significant importance for the formulation of relevant policies regarding the global GCRC burden. During the period from 1990 to 2021, the ASPR grew fastest in the high-income Asia-Pacific region (AAPC: 20.372 [95% CI: 19.430 to 21.315]), followed by East Asia (AAPC: 18.685 [95% CI: 18.328 to 19.041]) and the Caribbean (AAPC: 17.634 [95% CI: 17.053 to 18.215]). Western Europe not only has the highest number of cases but also shows a rapid growth trend in ASPR (AAPC: 11.059 [95% CI: 10.364 to 11.755]). In recent decades, due to multiple concurrent developments - including East Asia's economic growth, improved treatment options for geriatric patients [ 11 ] , and intensified aging trends [ 4 ] ,the burdern of GCRC has futher increased. Western European countries have established population-based CRC screening programs for secondary cancer prevention and this progress has been achieved by systematic invitation of eligible individuals via screening registries [ 26 , 27 ] . Although the number of cases in high SDI regions is the highest among all SDI regions, the rate of increase is not the fastest, and compared to prevalence rates, ASIR, ASMR, and ASDR have shown a declining trend from 1990 to 2021, with the most significant decline in ASDR (AAPC: -33.567 [95% CI: -34.003 to -33.131]). This is attributed to the improvement of public health services, progress in screening strategies, and therapeutic advancements in high-income countries [ 3 ] . Specifically, comprehensive early screening for colorectal cancer helps increase the detection rate of adenomas, thereby preventing their progression to colorectal cancer. As high-income countries gradually recognize the impact of the quality of care for the geriatric on cancer-related outcomes, the prognosis for GCRC patients has significantly improved [ 28 ] . Our study also reveals national-level trends. From 1990 to 2021, among 204 countries and regions, DALYs increased in 127 countries. Additionally, ASPR increased in 190 countries and regions, indicating that the burden of GCRC disease has increased in most countries. Socioeconomic factors such as educational attainment, health promotion initiatives, and preventive healthcare significantly influence these changes. According to statistics from the United States, geriatric colorectal cancer patients account for approximately 44% of the total patient population [ 2 ] . The 90-day postoperative mortality rate increases with age, reaching as high as 15.3% for those over 80 years old [ 29 ] . Moreover, obstructive colorectal cancer generally occurs in individuals aged 75 and older, often leading to complications such as intestinal perforation, septicemia, and bowel necrosis [ 30 , 31 ] . The ASMR and DALYs for GCRC are significantly higher when compared to all age groups: ASMR (156.7 [95% CI: 133.78 to 171.06] vs. 12.3 [95% CI: 11.2 to 13.3]), ASDR (2000.51 [95% CI: 1731.58-2177.48] vs. 283.2 [95% CI: 263.1-303.3]) [32]. Furthermore, these rates are also significantly higher than those in the early-onset colorectal cancer group: ASMR (2.30 [95% CI: 2.09 to 2.51]) and ASDR (115.42 [95% CI: 104.96 to 126.14]) [ 23 ] . On one hand, geriatric individuals are often affected by comorbidities, nutritional deficiencies, and physical impairments, which prevent them from completing necessary treatment regimens. A study conducted by Margalit D N et al. reported patients with deviations had a higher crude mortality rate than those without deviations [ 12 ] . Considering the competitive mortality among geriatric patients, shorter follow-up times, and impaired treatment tolerance [ 32 ] , the exclusion of geriatric patients from randomized clinical trials is another reason for the heavy burden of GCRC [ 7 ] . On the other hand, due to the low willingness of geriatric patients to participate in clinical trials, randomized controlled trials have not provided evidence for this population, leading to a gap in evidence and undermining the external validity of guidelines. It is urgent to strengthen measures aimed at alleviating the burden of GCRC, including expanding geriatric oncology expertise in guidelines, inviting geriatricians to participate in guideline development, improving comprehensive assessments and follow-up treatment plans, conducting thorough geriatric assessments to inform treatment decisions, and implementing targeted interventions to enhance quality of life, especially in China, Japan, the United States, and Germany, the top four countries with the highest incidence, mortality, prevalence, and DALYs. Among various colorectal cancer guidelines, Germany's AWMF guidelines include a dedicated chapter on geriatric oncology, developed based on the opinions of geriatricians [ 13 ] . Interestingly, Germany's GCRC mortality rate has decreased at the second-fastest rate from 1990 to 2021 (AAPC = -5.44 [95% CI: -5.69 to -5.18]), which is 4.8 times the global average (AAPC = -1.113 [95% CI: -1.138 to -1.089]). Similarly, the decline in DALY rates (AAPC: -66.41, 95% CI: -70.89 to -61.94) was 4.5 times faster than the worldwide average (AAPC: -14.832, 95% CI: -15.179 to -14.485). Despite the global decline in ASPR and ASMR, the incidence and mortality rates for males remain consistently higher than for females, and this gap is gradually widening. Some studies suggest that this outcome is due to physiological differences between the sexes [ 33 ] , while others indicate that gender-related sociocultural factors and behaviors, such as smoking, drinking, dietary habits, and BMI, play a role [ 34 ] . Gender mechanisms account for at least 30% of the total impact on CRC incidence [ 35 ] , which explains why the number of male cases exceeds that of females. Unlike premenopausal women, the physiological changes in geriatric women, after the removal of oral contraceptives and the weakening of estrogen's protective effects [ 36 ] , but significant sex-based disparities in GCRC burden still persist. Compared to females, males exhibit higher rates of harmful health risk behaviors, such as smoking, drinking, and obesity, with high BMI being a primary reason for the gender disparity in incidence rates [ 35 ] . Notably, China has the highest number of GCRC cases and disease burden in the world. China has experienced rapid socioeconomic development and urbanization, accompanied by decreased physical activity levels and the prevalence of Western dietary patterns [ 37 ] , making it the country with the highest number of obese individuals [ 38 ] , further exacerbating the disease burden. Our study indicates that screening, diagnosis, and intervention processes should be more focused on males. To further alleviate the burden of GCRC mortality and DALYs, effective policies should be formulated targeting the risk exposure of the geriatric population to minimize risk factors. This study confirms that a lack of whole grain diet, insufficient milk intake, and high red meat consumption are major dietary risk factors contributing to the GCRC burden. Moreover, these factors interact with a lifestyle lacking physical exercise, such as obesity. Adipose tissue is considered a natural reservoir for macrophages and inflammatory cytokines, and long-term exposure to chronic inflammation in obese individuals is believed to contribute to the development of colorectal cancer [ 39 ] . Due to co-occurrence of obesity (requiring prolonged operative time) and muscle atrophy amoung geiatric patients, the risks of both intraoperative bleeding and postoperative infection are significantly elevated [ 40 , 41 ] , further increasing the GCRC burden. This emphasizes the importance of public health interventions aimed at improving dietary habits and lifestyles to reduce the effect of mutiple factors on GCRC risks. Low milk and calcium intake are a major risk factor for CRC mortality in low-income countries. Calcium not only neutralizes bile acids in the intestinal lumen [ 42 ] , reducing intestinal permeability and thereby decreasing the absorption of harmful substances [ 43 ] , but also promotes the differentiation of rectal epithelial tissue [ 44 ] , reducing DNA damage in the rectal mucosa [ 45 ] . Addressing the widespread exposure to this risk factor in this region is necessary. In high-income countries, in addition to dietary factors, a lack of physical activity can be classified as a major risk factor for CRC mortality. The association between lack of physical exercise and colorectal cancer has been confirmed by most studies [ 46 ] . Specific preventive policies should be developed to reduce exposure to these risk factors and alleviate the burden of CRC. Possible interventions include increasing whole grain intake, reducing red meat and processed meat consumption, and raising public awareness of the importance of physical exercise through public health education, especially among populations exposed to modifiable factors. Identifying the main risk factors for exposure in specific regions based on gender and regional stratification can promote the formulation of specific policies to reduce exposure to risk factors in those areas. Our predictive model shows a concerning trend. Using the BAPC model, we predict that the prevalence burden of GCRC will further worsen by 2040, indicating that in the future, GCRC will remain a significant public health issue and challenge. Furthermore, the gender disparity in ASMR and ASDR are becoming increasingly pronounced, with the disease burden for males becoming heavier than for females. In the future, primary and secondary prevention of the disease should be prioritized, and the treatment details in disease guidelines for geriatric colorectal cancer patients, especially male patients, should continue to be refined to generate more clinical evidence and continuously improve care quality. Promoting healthier dietary and exercise habits tailored to different regions and genders is particularly important for alleviating the burden of this disease. This study also bears certain limitations. Firstly, since the data in the GBD database come from different countries and regions, the measurement bias and different treatment plans may be inevitable, which would influence the accuracy of the GCRC burden assessment. Second, due to data source constraints, we could not stratify between colon cancer and rectal cancer. Third, considering the physique variation of the geriatric population, this study did not delve into the impact of frailty assessments (such as Hospital Frailty Risk Score (HFRS), the Secondary Care Administrative Records Frailty (SCARF) index, and frailty syndromes (FS)) on CRC burden [ 47 ] , but these factors may have different impacts on CRC disease burden in different countries and regions. However, these limitations do not change the fact that this study gives a thorough look at the CRC burden among geriatric adults, which is valuable for disease control. 5. Conclusions In conclusion, this study reports the burden of global GCRC from 1990 to 2021. Although the ASMR and ASDR for GCRC have shown a declining trend over the past 32 years, the deaths cases and DALYs attributed to GCRC have doubled, along with the increase in ASPR, exhibited the latest trends and burdern of GCRC at the global. Our research emphasizes that among the geriatric population, males bear a greater burden of GCRC compared to females, highlighting the need for greater attention to screening, diagnosis, and treatment for males. Our findings indicate that a lack of whole grain diet, insufficient milk intake, high red meat consumption, and lack of physical exercise are four prominent risk factors contributing to the DALY and mortality burden of global GCRC in 2021. Targeted primary prevention is necessary to alleviate the burden of GCRC, and The findings from this analysis can contribute to the formulation of healthcare policies for policymakers, optimize healthcare resource allocation, while also aiding in the development of more comprehensive GCRC guidelines for geriatric patients. Abbreviations The following abbreviations are used in this manuscript: GCRC Geriatric Colorectal Cancer SDI Socio-demographic index ASR Age-standardized rate ASPR Age-standardized prevalence rate ASIR Age-standardized incidence rate ASMR Age-standardized mortality rate ASDR Age-standardized DALY rate DALYs Disability-adjusted life years Declarations Supplementary Materials : The following supporting information can be downloaded at: https://www.mdpi.com/article/doi/s1, Table S1: DALYs and death of geriatric colorectal cancer between 1990 and 2021. Table S2: Prevalence of 204 countries and regions.Table S3: Incidence of 204 countries and regions. Table S4: DALYs of 204 countries and regions. Author Contributions: Y.H.: Conceptualization, Visualization, Formal analysis, Writing—original draft, Writing—review and editing. S.W.: Investigation, Checking and modifying the manuscript, Project adminis tration. All authors have read and agreed to the published version of the manuscript. Funding : This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Clinical trial number : not applicable. Institutional Review Board Statement : The study did not require ethical approval. Informed Consent Statement: This was a retrospective, observational cohort study based on open access GBD database. Therefore, consent was not applicable. Data Availability Statement: The datasets used during the current study are available from the corresponding author upon reasonable request. Conflicts of Interest: The authors declare no conflicts of interest. References Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA. Cancer J. Clin., 2024, 74(3): 229-263. Siegel R L, Miller K D, Goding Sauer A, et al. Colorectal cancer statistics, 2020[J]. CA. Cancer J. Clin., 2020, 70(3): 145-164. Li N, Lu B, Luo C, et al. 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Sarno G, Simancas-Racines D, Gargiulo A, et al. Impact of obesity on postoperative complications in colorectal cancer surgery: A systematic review and meta-analysis[J]. Semin. Cancer Biol., 2025: S1044-579X(25)00074-4. Newmark H L, Wargovich M J, Bruce W R. Colon cancer and dietary fat, phosphate, and calcium: a hypothesis[J]. J. Natl. Cancer Inst., 1984, 72(6): 1323-1325. Schepens M A A, ten Bruggencate S J M, Schonewille A J, et al. The protective effect of supplemental calcium on colonic permeability depends on a calcium phosphate-induced increase in luminal buffering capacity[J]. Br. J. Nutr., 2012, 107(7): 950-956. Fedirko V, Bostick R M, Flanders W D, et al. Effects of Vitamin D and Calcium on Proliferation and Differentiation in Normal Colon Mucosa: A Randomized Clinical Trial[J]. Cancer Epidemiol. Biomark. Prev. Publ. Am. Assoc. Cancer Res. Cosponsored Am. Soc. Prev. Oncol., 2009, 18(11): 2933-2941. Fedirko V, Bostick R M, Long Q, et al. Effects of Supplemental Vitamin D and Calcium on Oxidative DNA Damage Marker in Normal Colorectal Mucosa: A Randomized Clinical Trial[J].Cancer Epidemiol. Biomark. Prev. Publ. Am. Assoc. Cancer Res. Cosponsored Am. Soc. Prev. Oncol., 2010, 19(1): 280-291. Stein M J, Baurecht H, Bohmann P, et al. Diurnal timing of physical activity and risk of colorectal cancer in the UK Biobank[J]. BMC Med., 2024, 22(1): 399. Montroni I, Ugolini G, Saur N M, et al. Predicting Functional Recovery and Quality of Life in Older Patients Undergoing Colorectal Cancer Surgery: Real-World Data From the International GOSAFE Study[J]. J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol., 2023, 41(34): 5247-5262. Table Table 1 is available in the Supplementary Files section. Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7297355","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":511496863,"identity":"c9db1af5-97a2-4d4f-92f1-52394c32b5aa","order_by":0,"name":"Yuwei Huo","email":"","orcid":"","institution":"Children's Hospital of Chongqing Medical University","correspondingAuthor":false,"prefix":"","firstName":"Yuwei","middleName":"","lastName":"Huo","suffix":""},{"id":511496864,"identity":"3622b703-d380-4a8d-848f-c39c0a1c11ca","order_by":1,"name":"Shengde Wu","email":"data:image/png;base64,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","orcid":"","institution":"Children's Hospital of Chongqing Medical University","correspondingAuthor":true,"prefix":"","firstName":"Shengde","middleName":"","lastName":"Wu","suffix":""}],"badges":[],"createdAt":"2025-08-05 07:08:34","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7297355/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7297355/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":91193012,"identity":"a2396624-3ec1-4f93-869d-a52dad723f3c","added_by":"auto","created_at":"2025-09-12 14:43:59","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":135707,"visible":true,"origin":"","legend":"\u003cp\u003eTrends of global burden of geriatric colorectal cancer, 1990 to 2021. DALYs, disability-adjusted life-years. Data expressed as age-standardized rates per 100,000 population\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7297355/v1/f8da815f7d0057a99a67ffa3.png"},{"id":91193021,"identity":"1a4ee0fc-32e0-496e-83cf-5ececda0b293","added_by":"auto","created_at":"2025-09-12 14:43:59","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":532025,"visible":true,"origin":"","legend":"\u003cp\u003eGlobal map of the national burden of geriatric colorectal cancer in 2021. ASR, age-standardized rate; DALYs, disability-adjusted life-years. Data expressed as ASRs per 100,000 population.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7297355/v1/23ac43ed01532f3676a8bde1.png"},{"id":91194340,"identity":"bc8f1029-1301-4fd0-8e52-5ed3e38489e1","added_by":"auto","created_at":"2025-09-12 14:51:59","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":100437,"visible":true,"origin":"","legend":"\u003cp\u003eDecomposition analysis of changes in the burden of geriatric colorectal cancer by SDI, 1990 to 2021. DALYs, disability-adjusted life-years; SDI, sociodemographic index. 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DALYs, disability-adjusted life-years; SDI, sociodemographic index.\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-7297355/v1/6e29e855b3adf9ecdddf3351.png"},{"id":91194341,"identity":"380dc4e1-b9e4-4fb5-8986-c159cbb0ce3b","added_by":"auto","created_at":"2025-09-12 14:51:59","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":443805,"visible":true,"origin":"","legend":"\u003cp\u003ePercentage contribution of 11 risk factors to the deaths and DALYs burden of geriatric colorectal cancer on global level and 21 GBD regions in 2021. DALYs: Disability-adjusted life years; GCRC: Geriatric Colorectal Cancer; GBD: Global Burden of Diseases, Injuries, and Risk Factors Study.\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-7297355/v1/d9c778624af8f0fed81d6dae.png"},{"id":91195877,"identity":"0e34d929-af08-4ec3-884f-e25fa9a15f30","added_by":"auto","created_at":"2025-09-12 15:00:00","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":225267,"visible":true,"origin":"","legend":"\u003cp\u003ePredictions of the global burden of geriatric colorectal cancer, 2022 to 2040. DALYs, disability-adjusted life-years\u003c/p\u003e","description":"","filename":"6.png","url":"https://assets-eu.researchsquare.com/files/rs-7297355/v1/15bba2d108212f8633bb40dd.png"},{"id":95227663,"identity":"9849cdc8-274d-4a4a-87e0-cce2e313469e","added_by":"auto","created_at":"2025-11-05 16:32:43","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1986766,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7297355/v1/07da19d5-31cd-4c7c-9aa8-d6024aab09a1.pdf"},{"id":91194339,"identity":"36f68877-b5a4-4c64-b419-a67be3edcc80","added_by":"auto","created_at":"2025-09-12 14:51:59","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":215554,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementarydata.docx","url":"https://assets-eu.researchsquare.com/files/rs-7297355/v1/f17f6cc026341724a107e0f7.docx"},{"id":91194338,"identity":"5d8787da-26b9-4a72-a860-ea2e62e93f21","added_by":"auto","created_at":"2025-09-12 14:51:59","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":24644,"visible":true,"origin":"","legend":"","description":"","filename":"Table1.docx","url":"https://assets-eu.researchsquare.com/files/rs-7297355/v1/d0b8606514cb1d55161f67d5.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Evolving landscape of geriatric colorectal cancer: Global and regional burden, risk factor dynamics, and future scenarios (the Global Burden of Disease 1990–2040)","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eAccording to the latest statistics data from the International Agency for Research on Cancer, colorectal cancer (CRC) was the third most prevalent malignancy globally and the second leading cause of cancer-related mortality in 2022\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e. The incidence of colorectal cancer increases with age, with approximately 88% of cases occurring in individuals over 50 years old\u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e. Despite the significant progress has been achieved in screening for colorectal cancer in recent decades\u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e, the number of geriatric individuals diagnosed with colorectal cancer increasing year by year owing to the increasing global life expectancy and the rising proportion of the geriatric population\u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e. According to estimates provided by the International Agency for Research on Cancer of the World Health Organization, it is estimated that there will be 1.9\u0026nbsp;million new cases and 904,000 deaths in 2022. Furthermore, there is a significant global disparity in the burden of CRC, with the incidence in completed transition countries being 3 to 4 times higher than in transitioning countries. The highest incidence rates are found in Europe, Australia and North America. Conversely, Africa, South Asia, and Central Asia have relatively lower incidence rates\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e. Another study shows that due to socioeconomic inequalities, the mortality rate of colorectal cancer patients in poverty rural areas is 1.2 to 1.6 times higher than in other regions\u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e. The large number of patients presents a significant global health challenge.\u003c/p\u003e\u003cp\u003eThe heterogeneity of geriatric patients is significant. On one hand, geriatric patients in optimal physical and mental condition may miss opportunities for radical treatment due to overly conservative treatment plans; on the other hand, frail patients may face serious complications when receiving intensive treatment\u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e. This clinical decision-making dilemma as a result of the lack of large-scale cohort studies targeting geriatric patients, leading to a lack of high-quality evidence to support treatment standards\u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e. For example, adjuvant chemotherapy or surgical plans developed based on data from younger patients may not be applicable to geriatric patients with complex comorbidities. Additionally, existing data often focus on traditional endpoint indicators such as survival rates, with inadequate consideration to the disease-associated burden on patients, including quality of life and functional recovery\u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e, resulting in a lack of research on the disease burden of colorectal cancer patients over 75 years old. The Global Burden of Disease (GBD) database, created and managed by the Institute for Health Metrics and Evaluation (IHME), aims to provide detailed global information on diseases, injuries, and risk factors\u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e, offering a unique opportunity.\u003c/p\u003e\u003cp\u003eWe present the global trends in age standerdized rate of disability-adjusted life years (DALYs), deaths, prevalence and incidence from GCRC between 1990 and 2021 using GBD2021 data and provide forecasts for the burden of GCRC up to 2040. We also conducted decomposition analysis and risk factor analysis to examine the main driving factors behind the changes in GCRC burden, as well as an analysis of health inequalities to determine the relationship between SDI and GCRC burden. This provides a basis for developing geriatric-friendly screening guidelines and stratified treatment strategies.\u003c/p\u003e"},{"header":"2. Materials and Methods","content":"\u003cp\u003eData Source\u003c/p\u003e\u003cp\u003eThe data utilized in this research was obtained from the GBD 2021 database through the Global Health Data Exchange (GHDx) query tool (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://vizhub.healthdata.org/\u003c/span\u003e\u003cspan address=\"https://vizhub.healthdata.org/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e gbd-results/), which provides data on the burden of 371 diseases and injuries in 21 GBD regions and 204 countries and territories between 1990 and 2021, including CRC\u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e. The methodologies employed in GBD 2021 have been detailed in previously published articles\u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e. This study complied with the Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER) \u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e. Ethics approval was not required for this study due to the analysis of anonymized and publicly available data.\u003c/p\u003e\u003cp\u003eDefinition of Geriatric Colorectal Cancer (GCRC)\u003c/p\u003e\u003cp\u003eIn this study, colorectal cancer (CRC) was identified using ICD-11 codes C18\u0026ndash;21, D01.0\u0026ndash;D01.2, and D12\u0026ndash;D12.9, encompassing both colon and rectal cancer. In accordance with previous studies, Geriatric Colorectal Cancer (GCRC) was defined as diagnoses or prevalences occurring aged 75 years and above\u003csup\u003e[\u003cspan additionalcitationids=\"CR12 CR13 CR14\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e. In this study, we designated the terms \u0026ldquo;colon and rectum cancer\u0026rdquo; as the \u0026ldquo;cause\u0026rdquo;, while \u0026ldquo;incidence\u0026rdquo;, \u0026ldquo;deaths\u0026rdquo;,\u0026ldquo;prevalence\u0026rdquo;and \u0026ldquo;DALYs\u0026rdquo; were identified as the \u0026ldquo;measures\u0026rdquo;. And we collected in 5 age groups (\"75\u0026ndash;79 years\",\"80\u0026ndash;84 years\",\"85\u0026ndash;89 years\",\"90\u0026ndash;94 years\",\"95\u0026thinsp;+\u0026thinsp;years\"). All data analyses for this investigation were finalized on April 1, 2025. Analyses were stratified by sex, socio-demographic index (SDI), and 21 GBD-defined regions (which were 21 groups of countries/territories that were geographically proximate and epidemiologically similar), such as High-Income North America, Southeast Asia, and Western Sub-Saharan Africa.\u003c/p\u003e\u003cp\u003eEstimation of incidence, deaths, prevalence and DALYs\u003c/p\u003e\u003cp\u003eThe estimates of incidence, deaths, prevalence and disability-adjusted life years (DALYs) for GCRC were derived from the Global Burden of Disease (GBD) 2021 dataset. DALYs were calculated as the sum of years of life lost (YLLs) and years lived with disability (YLDs), with one DALY representing the loss of one year of healthy life. All rates (incidence, prevalence, mortality, and DALYs) were expressed per 100,000 individuals. To account for variations in population age structures across regions and countries\u0026mdash;which could distort crude rate comparisons\u0026mdash;we employed age-standardized rates (ASRs) using the world standard population from GBD 2021 as the reference \u003csup\u003e[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/sup\u003e. Specifically, we calculated age-standardized incidence (ASIR), mortality (ASMR), prevalence (ASPR) and DALY (ASDR) rates (per 100,000 population) via this formula:\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003ewhere ai is the age-specific rate in the ith age group, wi is the weight in the same age subgroup of the chosen reference standard population (in which i denotes the ith age class), and A is the total number of age groups\u003csup\u003e[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/sup\u003e.This approach minimized confounding by age disparities, enabling more accurate cross-regional assessments of the GCRC burden.\u003c/p\u003e\u003cp\u003eRisk factors\u003c/p\u003e\u003cp\u003eWe obtained risk factors data from the GBD 2021 database, which mainly includes three categories: environment/occupational risks, behavioral risks, and metabolic risks. According to previous literature\u0026rsquo;s evidence, we selected 11 risk factors that have contribution to DALYs and deaths, including 6 dietary related factors(Diet low in whole grains, Diet low in fiber, Diet low in milk, Diet low in calcium, Diet high in red meat, Diet high in processed meat), 3 behavioral related factors(High alcohol use, Smoking, Low physical activity) and 2 metabolic related factors(High fasting plasma glucose, High body-mass index). The contribution percentage of these risk factors to DALYs and mortality will be analyzed visually.\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStatistical analysis\u003c/h2\u003e\u003cp\u003eWe used the \"segment\" package in R for joinpoint analysis to assess the average annual percentage change (AAPC) trends of GCRC's ASIR, ASMR, ASPR, and ASDR burden from 1990 to 2021, with the 95% confidence intervals (CIs) for AAPC derived from linear regression models. The specific calculation methods have been described in previous studies\u003csup\u003e[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/sup\u003e. When both AAPC and its 95% CI are \u0026gt;\u0026thinsp;0 (or \u0026lt;\u0026thinsp;0), the result is considered statistically significant, indicating an upward (or downward) trend, while if AAPC or its 95% CI includes 0, the change is deemed statistically insignificant, indicating a stable trend.\u003c/p\u003e\u003cp\u003eTo understand the contributions of aging, population growth, and epidemiological changes to the variations in incidence, prevalence, mortality, and DALY rates, this study conducted a decomposition analysis to reveal the impacts of these three factors on disease burden changes across different SDI regions. SDI is a composite indicator measuring the level of social development, ranging from 0 to 1, indicating from least developed to most developed. All countries were classified into five categories according to the SDI: Low SDI: SDI\u0026thinsp;\u0026lt;\u0026thinsp;0.46; Low-middle SDI: 0.46\u0026ndash;0.64; Middle SDI: 0.65\u0026ndash;0.74; High-middle SDI: 0.75\u0026ndash;0.85; High SDI: SDI\u0026thinsp;\u0026gt;\u0026thinsp;0.85\u003csup\u003e[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eTo further assess the impact of socioeconomic levels on disease burden, we used slope index of inequality (SII) and concentration index (CI) to evaluate the absolute and relative inequalities in DALY rates.Slope index of inequality was calculated by regression of the country-level DALYs due to GCRC within populations aged 75+, utilizing a scale that reflects relative positioning based on sociodemographic development, defined by the midpoint of the cumulative class range of the population ranked by the Socio-Demographic Index (SDI). The concentration index of health inequality was calculated by fitting a Lorenz concentration curve to the observed cumulative relative distribution of populations ranked by SDI alongside the disease-related DALYs, and involved numerically integrating the area beneath the curve\u003csup\u003e[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e. The 95% CI was calculated using the \"Boot\" package in R language. A larger slope index of inequality indicates that high SDI regions bear a greater disease burden, and vice versa\u003csup\u003e[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/sup\u003e. The range of the concentration index is from \u0026minus;\u0026thinsp;1 to 1, where negative values indicate that the disease burden is more prevalent among lower socioeconomic groups, and vice versa\u003csup\u003e[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eThe Bayesian age-period-cohort (BAPC) model was used to project the burden of GCRC to 2040. We used the \"BAPC\" and \"INLA\" packages in R to predict the incidence, mortality, prevalence, and DALY rates of GCRC from 2022 to 2040. The BAPC model is a commonly used method for understanding disease trend changes, based on the classical age-period-cohort model, especially in studies involving age-structured population data and complex cohort effects\u003csup\u003e[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/sup\u003e.All statistical analyses and visualization were finished using R software (version 4.5.0).\u003c/p\u003e\u003c/div\u003e"},{"header":"3. Results","content":"\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\n \u003ch2\u003e3.1. Disease Burden Due to Geriatric Colorectal Cancer by Regions and Countries\u003c/h2\u003e\n \u003cp\u003eFrom 1990 to 2021, the number of cases of GCRC significantly increased, nearly tripling from 1,024,219 (95% UI: 938,349 to 1,103,818) in 1990 to 2,919,947 (95% UI: 2,602,420 to 3,137,886) in 2021, as detailed in Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e. The ASIR rose from 244.78 (95% UI: 217.78 to 258.85) per 100,000 to 274.11 (95% UI: 210.71 to 269.75) per 100,000, indicating only a slight increase in incidence (AAPC: 0.090 [95% CI: 0.048 to 0.133], p\u0026thinsp;\u0026lt;\u0026thinsp;0.001)(Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). The number of deaths from colorectal cancer was 207,829 (95% UI: 187,252 to 218,367) in 1990, corresponding to an ASMR of 191.71 (95% UI: 170.69 to 203.03) per 100,000; by 2021, the number of deaths from the disease rose to 443,460 (95% UI: 385,191 to 479,790), with the corresponding ASMR decreasing to 156.70 (95% UI: 133.78 to 171.06) per 100,000, indicating a significant downward trend (AAPC: -1.113 [95% CI: -1.138 to -1.089], p\u0026thinsp;\u0026lt;\u0026thinsp;0.001)(Supplementary Table 1, Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). Over the same period, the ASPR increased from 873.28 (95% UI: 783.73 to 960.16) to 1010.94 (95% UI: 884.13 to 1,095.40) (AAPC: 4.491 [95% CI: 4.347 to 4.635], p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The ASDR exhibited a significant downward trend, decreasing from 2,462.35 (95% UI: 2,218.50 to 2,602.57) per 100,000 to 2,000.51 (95% UI: 1,731.58 to 2,177.48) per 100,000 (AAPC: -14.832 [95% CI: -15.179 to -14.485], p\u0026thinsp;\u0026lt;\u0026thinsp;0.001)(Supplementary Table 1, Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). In 2021, around 2,919,947 (95% UI: 2,602,420 to 3,137,886) colorectal cancer patients worldwide accounted for 5,728,257 (95% UI: 5,038,383 to 6,201,686) DALYs.\u003c/p\u003e\n \u003cp\u003eIn terms of gender, in 1990, the global male ASPR rate (957.14 per 100,000 population) was higher than that of females (820.97 per 100,000 population). By 2021, this trend continued, with the male ASPR rising to 1243.06 per 100,000 population, while the female ASRP remained stable, with only a slight increase to 840.72 per 100,000 population(Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e, Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003eA). The global male ASIR rate (276.5 per 100,000 population) was higher than that of females (225.1 per 100,000 population). By 2021, the male ASIR continued to rise to 308.78 per 100,000 population, while the female ASIR decreased to 202.88 per 100,000 population(Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e, Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003eB). During this period, the ASDR decreased for both genders, with the male ASDR dropping from 2814.1 per 100,000 to 2487.3 per 100,000 (AAPC: -10.573 [95% CI: -11.232 to -9.913], P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and the female ASDR decreasing from 2243.7 per 100,000 to 1650.6 per 100,000 (AAPC: -19.099 [95% CI: -19.430 to -18.768], P\u0026thinsp;\u0026lt;\u0026thinsp;0.001)(Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003eC). Between 1990 and 2021, the number of deaths attributed to GCRC among males increased from 89,009 to 220,890, with the ASMR showing a downward trend, decreasing from 217.12 to 193.50 per 100,000 population (AAPC: -0.715 [95% CI: -0.759 to -0.672], P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). For females, the number rose from 118,820 to 222,570, and the ASMR showed a more pronounced downward trend compared to males: decreasing from 176.31 to 131.13 per 100,000 population (AAPC: -1.433 [95% CI: -1.469 to -1.397], P\u0026thinsp;\u0026lt;\u0026thinsp;0.001)(Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e, Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003eD). Males accounted for approximately 42.8% of the deaths in 1990, and by 2021, this proportion gradually increased to 49.8%.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\n \u003ch2\u003e3.2 Burden of colorectal cancer in regions\u003c/h2\u003e\n \u003cp\u003eAmong the 5 SDI regions, the highest ASPR, ASIR, ASMR, and ASDR were observed in the high-SDI region. From 1990 to 2021, ASPR showed an increasing trend across all SDI regions, while ASMR and ASDR exhibited a decreasing trend in the high-SDI and high-middle SDI regions, with the most significant decrease trend was noted in the former region, while the remaining SDI regions showed an increasing trend. ASIR increased in all SDI regions except for the high-SDI region.\u003c/p\u003e\n \u003cp\u003eAmong the 21 regions, the highest ASPR was in Australasia(2,301.63/100,000[95% UI: 1,914.34 to 2,664.97]), closely followed by High-income Asia Pacific (2,243.00/100,000 [95% UI: 1,853.27 to 2,533.56]). Western Europe had the highest cases amoung all regions, with 818,023 cases (95% UI: 717,449 to 887,045), accounting for approximately 28.01% (1/4) of the global cases(Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). The highest ASMR was founded in Central Europe (267.79/100,000 [95% UI: 239.44 to 289.60]), followed by Southern Latin America (224.58/100,000 [95%UI:185.60 to 261.10]) and Western Europe(213.72/100,000 [95% UI: 176.86 to 236.08]). The highest ASIR was in Australasia (442.00/100,000[95% UI: 359.34 to 520.69]),followed by Western Europe (392.74/100,000 [95% UI: 330.44 to 432.33]). The greatest incidence number of GCRC patients was founded in East Asia (175,842 [95%UI:144,279 to 203,627]), closely followed by Western Europe (174,264 [95%UI:146,380 to 191,164]). In 2021, the highest ASDR was in Central Europe (3,499.61/100,000[95% UI: 3,154.45 to 3,777.20]), followed by Southern Latin America (2,863.06/100,000[95% UI: 2,381.49 to 3,326.31]), while the highest DALYs was in East Asia(1,444,133 [95%UI:1,194,325 to 1,689,659]), followed by Western Europe(1,226,711 [95%UI:1,026,464 to 1,348,462])(Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\n \u003ch2\u003e3.3 Country burden of GCRC\u003c/h2\u003e\n \u003cp\u003eIn 2021, the GCRC prevalence count and ASPR recorded in China, Japan, and the United States were the highest(Supplementary Table\u0026nbsp;2). China reported 612,442 cases (95% UI 509,330 to 709,364) with an ASPR of 3,966.58 per 100,000 (3,310.82 to 4,594.06). Japan followed with 434,854 cases (362,207 to 478,819) with ASPR of 3,141.68 per 100,000 (2,362.74 to 3,985.97), while the United States recorded 366,053 cases (320,593 to 394,333) with ASPR of 3,088.49 per 100,000 (2,446.85 to 3,889.14). Gambia had the lowest ASPR (56.37/100,000 [95% UI: 41.98 to 74.23]). These three nations\u0026mdash;China, Japan, and the United States\u0026mdash;recorded the highest total numbers of incident cases of GCRC as well, with respective counts of 168,546 (137,582 to 196,316), 87,720 (69,624 to 98,554), and 72,602 (60,132 to 79,110)(Supplementary Table\u0026nbsp;3). In terms of ASIR, Netherlands led with 707.21 (573.19 to 833.05), followed by Monaco at 674.79 (495.51 to 889.99), and Bermuda at 659.84 (514.26 to 840.91). Papua New Guinea exhibited the lowest ASIR at 29.57 per 100,000 (95% UI: 20.99 to 40.08). Regarding DALYs, China reported the highest number of cases with 1,374,963 (1,121,844 to 1,623,509), Japan with 550,362 (437,544 to 614,325), and the United States with 453,047 (382,069 to 493,830)(Supplementary Table\u0026nbsp;4). Conversely, Monaco had the highest ASDR at 4,709.98 (3,477.97 to 6,088.76), followed by Uruguay at 4,593.30 (3,797.01 to 5,399.79) and Croatia at 4,155.30 (3,411.49 to 4,983.01). Bangladesh reported the lowest ASDR at 432.48 per 100,000 (95% UI: 302.46 to 617.79). The first three countries for deaths in terms of ASMR were the same: China with 101,647 deaths (83,034 to 118,761) and an ASMR of 362.72 (298.30 to 429.53), Japan with 46,058 deaths (35,684 to 51,842) and an ASMR of 362.16 (264.00 to 472.89), and the United States with 35,143 deaths (28,959 to 38,553) and an ASMR of 319.51 (261.64 to 383.75). Papua New Guinea had the lowest ASDR at 34.43 per 100,000 (95% UI: 24.48 to 46.81)(Supplementary Table\u0026nbsp;5).\u003c/p\u003e\n \u003cp\u003eDuring the period from 1990 to 2021, among 204 countries and regions, 192 countries showed an increasing trend in ASPR, with 30 countries/regions having prevalence cases that doubled or more(Supplementary Table 2, Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003eA). The greatest increase countries were Bermuda (AAPC: 46.86 [95% CI: 43.59 to 50.13]), Republic of Korea (AAPC: 45.03 [95% CI: 43.57 to 46.49]), and Monaco (AAPC: 37.9 [95% CI: 36.84 to 38.96]). The GCRC ASIR increased in 172 countries and regions (Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003eB), with the significant increase of ASIR was observed in Republic of Korea, rising from 171.07 per 100,000 people (95% UI: 135.22 to 210.68) to 395.87 per 100,000 people (95% UI: 290.43 to 515.58), with an AAPC of 7.11 (95% CI: 6.64 to 7.58). While the greatest declines were observed in San Marino (AAPC: -8.41 [95% CI: -9.46 to -7.37]), Austria (AAPC: -4.84 [95% CI: -5.02 to -2.97]), and the United States of America (AAPC: -4.24 [95% CI: -4.44 to -4.04])(Supplementary Table\u0026nbsp;3).\u003c/p\u003e\n \u003cp\u003eThe ASDR of GCRC in 133 countries and territories showed escalating trend (Supplementary Table 4 Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003eC), with Romania experiencing the fastest growth, increasing from 1,374.01 per 100,000 people (95% UI: 1,150.27 to 1,624.26) to 2,933.52 per 100,000 people (95% UI: 2,433.71 to 3,518.88), with an AAPC of 51.41 (95% CI: 48.45 to 54.37). Meanwhile, 71 countries showed a downward trend. San Marino had the fastest decline (AAPC: -82.91 [95% CI: -90.31 to -75.51]), followed by Greenland (AAPC: -71.22 [95% CI: -75.80 to -66.64]) and Germany (AAPC: -66.41 [95% CI: -70.89 to -61.94]). In 71 countries/regions, ASMR showed a decreasing trend(Supplementary Table 5, Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003eD). The greatest declines in ASMR were observed in San Marino (AAPC: -6.89 [95% CI: -7.45 to -6.33]), Germany (AAPC: -5.44 [95% CI: -5.69 to -5.18]), and Greenland (AAPC: -5.21 [95% CI: -5.60 to -4.83]). Meanwhile, Romania showed the greatest increase, from 103.70 (86.10-122.87) per 100,000 to 215.55(178.60-259.16) per 100,000, with an AAPC of 3.66 (95% CI 3.45 to 3.88).\u003c/p\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\n \u003ch2\u003e3.4 Decomposition analysis of GCRC\u003c/h2\u003e\n \u003cp\u003eFigure \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e shows the impact of population growth, aging, and epidemiological changes on GCRC changes. From 1990 to 2021, the changes in prevalence among the GCRC population were primarily due to population growth. This was more pronounced in high SDI regions as well as low SDI regions, while in middle SDI and high-middle SDI regions, it was influenced by epidemiological changes as well. Notably, while epidemiological changes contributed to the increase in incidence and prevalence, they played a mitigating role in mortality and DALYs rates.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\n \u003ch2\u003e3.5. Health inequalities of GCRC\u003c/h2\u003e\n \u003cp\u003eThe inequality slope index of DALY rate is positive, indicating that as the SDI increases, the burden borne by GCRC becomes heavier. From 1990 to 2021, the inequality slope decreased from 3143.82 to 2108.51, indicating that the absolute level of inequality is shrinking(Fig. \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e). The concentration index in ASDR is negative, indicating that both low and high SDI countries bear a greater burden of GCRC. In 2021, the concentration index decreased(Fig. \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e), the relative level of inequality is shrinking.\u003c/p\u003e\n \u003cp\u003eFigure \u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003e shows the burden of 11 risk factors on GCRC disease mortality and DALY in 21 GBD regions in 2021. Dietary deficiencies in whole grains(deaths: 17.9%, DALYs: 17.9%), lack of milk(deaths: 14.9%, DALYs: 14.8%), high intake of red meat(deaths: 14.7%, DALYs: 14.8%), and lack of physical exercise(deaths: 9.8%, DALYs: 9.5%) are the main causes of mortality and DALY, while obesity(deaths: 8.8%, DALYs: 8.9%), low calcium intake(deaths: 8.2%, DALYs: 8.2%), high consumption of processed meats(deaths: 5.7%, DALYs: 5.7%), high fasting plasma glucose(deaths: 8.9%, DALYs: 8.9%), low dietary fiber intake(deaths: 1.4%, DALYs: 1.3%), as well as smoking(deaths: 3.1%, DALYs: 3.3%) and drinking(deaths: 4.4%, DALYs: 4.5%) had less contribution to deaths and DALYs. The lack of whole grain nutrition is a common risk across all regions. The impact of different risk factors on mortality and DALY in geriatric patients varies by region, with the main risk factors in high SDI countries including lack of exercise, obesity, and excessive consumption of processed meats, while in low SDI countries, the primary causes are due to lack of milk and calcium.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e\n \u003ch2\u003e3.6.Prediction of disease burden of EOCRC from 2022 to 2040\u003c/h2\u003e\n \u003cp\u003eAccording to the BAPC model prediction, it is expected that from 2022 to 2040, the ASPR will continue to rise. By 2040, the global ASPR is projected to escalate to 1087.4698 [95%CI: 405.7223, 1769.2172](Fig. \u003cspan class=\"InternalRef\"\u003e6\u003c/span\u003eA), while ASDR, ASMR, and ASIR show a downward trend, decreasing to (240.3985 [95%CI: 98.03321, 382.7638])(Fig. \u003cspan class=\"InternalRef\"\u003e6\u003c/span\u003eB), (1663.487 [95%CI: 709.2769, 2617.698])(Fig. \u003cspan class=\"InternalRef\"\u003e6\u003c/span\u003eC) and (128.2597 [95%CI: 58.39403, 198.1253])(Fig. \u003cspan class=\"InternalRef\"\u003e6\u003c/span\u003eD) by 2040, with gender differences further widening. It is noteworthy that men still bear a heavier GCRC burden, with the ASPR for men rising more significantly in the future (1379.0179 [95%CI: 472.8397, 2285.1960]) compared to women (865.5796 [95%CI: 317.7059, 1413.4533])(Fig. \u003cspan class=\"InternalRef\"\u003e6\u003c/span\u003eA).\u003c/p\u003e\n\u003c/div\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eBased on the 2021 GBD database, this study explores the burden and trends of global, regional, and national GCRC (75+) from 1990 to 2021. Over the past 32 years, the number of geriatric individuals suffering from diseases, incidence, mortality, and total DALYs has shown a significant increase globally. Specifically, the number of global GCRC cases has nearly tripled since 1990, accompanied by a notable rise in ASPR, especially among the male population. Through decomposition analysis, we found that population growth is the primary reason for the increase in current cases, followed by changes in epidemiology. Although an increase in both death counts and DALYs, reaching 2.13 fold and 2.02 fold of the original values respectively, the ASMR and ASDR for both sexes show a steady decline. From 1990 to 2021, contrary to the rising trend of EOCRC incidence reported in the literature\u003csup\u003e[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/sup\u003e, the ASIR trend for geriatric patients remains stable, with female GCRC declining globally. However, the ASIR in males showed an overall upward trend and remained higher than in females. In regions with medium-high and high SDI, ASMR, ASIR, and ASDR show a declining trend, while in low, low-middle, and middle SDI regions, these indicators have been increasing year by year. This association may be attributed to enhanced public health awareness, widespread adoption of early screening programs, improved healthcare standards and optimized health insurance systems in middle-high and high SDI regions\u003csup\u003e[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]\u003c/sup\u003e. It is expected that by 2040, both male and female ASPR will rise, indicating that the burden of geriatric colorectal cancer will gradually increase in the future, which is of significant importance for the formulation of relevant policies regarding the global GCRC burden.\u003c/p\u003e\u003cp\u003eDuring the period from 1990 to 2021, the ASPR grew fastest in the high-income Asia-Pacific region (AAPC: 20.372 [95% CI: 19.430 to 21.315]), followed by East Asia (AAPC: 18.685 [95% CI: 18.328 to 19.041]) and the Caribbean (AAPC: 17.634 [95% CI: 17.053 to 18.215]). Western Europe not only has the highest number of cases but also shows a rapid growth trend in ASPR (AAPC: 11.059 [95% CI: 10.364 to 11.755]). In recent decades, due to multiple concurrent developments - including East Asia's economic growth, improved treatment options for geriatric patients\u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e, and intensified aging trends\u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e ,the burdern of GCRC has futher increased. Western European countries have established population-based CRC screening programs for secondary cancer prevention and this progress has been achieved by systematic invitation of eligible individuals via screening registries\u003csup\u003e[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]\u003c/sup\u003e. Although the number of cases in high SDI regions is the highest among all SDI regions, the rate of increase is not the fastest, and compared to prevalence rates, ASIR, ASMR, and ASDR have shown a declining trend from 1990 to 2021, with the most significant decline in ASDR (AAPC: -33.567 [95% CI: -34.003 to -33.131]). This is attributed to the improvement of public health services, progress in screening strategies, and therapeutic advancements in high-income countries\u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e. Specifically, comprehensive early screening for colorectal cancer helps increase the detection rate of adenomas, thereby preventing their progression to colorectal cancer. As high-income countries gradually recognize the impact of the quality of care for the geriatric on cancer-related outcomes, the prognosis for GCRC patients has significantly improved\u003csup\u003e[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eOur study also reveals national-level trends. From 1990 to 2021, among 204 countries and regions, DALYs increased in 127 countries. Additionally, ASPR increased in 190 countries and regions, indicating that the burden of GCRC disease has increased in most countries. Socioeconomic factors such as educational attainment, health promotion initiatives, and preventive healthcare significantly influence these changes. According to statistics from the United States, geriatric colorectal cancer patients account for approximately 44% of the total patient population\u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e. The 90-day postoperative mortality rate increases with age, reaching as high as 15.3% for those over 80 years old\u003csup\u003e[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]\u003c/sup\u003e. Moreover, obstructive colorectal cancer generally occurs in individuals aged 75 and older, often leading to complications such as intestinal perforation, septicemia, and bowel necrosis\u003csup\u003e[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]\u003c/sup\u003e. The ASMR and DALYs for GCRC are significantly higher when compared to all age groups: ASMR (156.7 [95% CI: 133.78 to 171.06] vs. 12.3 [95% CI: 11.2 to 13.3]), ASDR (2000.51 [95% CI: 1731.58-2177.48] vs. 283.2 [95% CI: 263.1-303.3]) [32]. Furthermore, these rates are also significantly higher than those in the early-onset colorectal cancer group: ASMR (2.30 [95% CI: 2.09 to 2.51]) and ASDR (115.42 [95% CI: 104.96 to 126.14])\u003csup\u003e[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/sup\u003e. On one hand, geriatric individuals are often affected by comorbidities, nutritional deficiencies, and physical impairments, which prevent them from completing necessary treatment regimens. A study conducted by Margalit D N et al. reported patients with deviations had a higher crude mortality rate than those without deviations\u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e. Considering the competitive mortality among geriatric patients, shorter follow-up times, and impaired treatment tolerance\u003csup\u003e[\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]\u003c/sup\u003e, the exclusion of geriatric patients from randomized clinical trials is another reason for the heavy burden of GCRC\u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e. On the other hand, due to the low willingness of geriatric patients to participate in clinical trials, randomized controlled trials have not provided evidence for this population, leading to a gap in evidence and undermining the external validity of guidelines. It is urgent to strengthen measures aimed at alleviating the burden of GCRC, including expanding geriatric oncology expertise in guidelines, inviting geriatricians to participate in guideline development, improving comprehensive assessments and follow-up treatment plans, conducting thorough geriatric assessments to inform treatment decisions, and implementing targeted interventions to enhance quality of life, especially in China, Japan, the United States, and Germany, the top four countries with the highest incidence, mortality, prevalence, and DALYs. Among various colorectal cancer guidelines, Germany's AWMF guidelines include a dedicated chapter on geriatric oncology, developed based on the opinions of geriatricians\u003csup\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e. Interestingly, Germany's GCRC mortality rate has decreased at the second-fastest rate from 1990 to 2021 (AAPC = -5.44 [95% CI: -5.69 to -5.18]), which is 4.8 times the global average (AAPC = -1.113 [95% CI: -1.138 to -1.089]). Similarly, the decline in DALY rates (AAPC: -66.41, 95% CI: -70.89 to -61.94) was 4.5 times faster than the worldwide average (AAPC: -14.832, 95% CI: -15.179 to -14.485).\u003c/p\u003e\u003cp\u003eDespite the global decline in ASPR and ASMR, the incidence and mortality rates for males remain consistently higher than for females, and this gap is gradually widening. Some studies suggest that this outcome is due to physiological differences between the sexes\u003csup\u003e[\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]\u003c/sup\u003e, while others indicate that gender-related sociocultural factors and behaviors, such as smoking, drinking, dietary habits, and BMI, play a role\u003csup\u003e[\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]\u003c/sup\u003e. Gender mechanisms account for at least 30% of the total impact on CRC incidence\u003csup\u003e[\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]\u003c/sup\u003e, which explains why the number of male cases exceeds that of females. Unlike premenopausal women, the physiological changes in geriatric women, after the removal of oral contraceptives and the weakening of estrogen's protective effects\u003csup\u003e[\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]\u003c/sup\u003e, but significant sex-based disparities in GCRC burden still persist. Compared to females, males exhibit higher rates of harmful health risk behaviors, such as smoking, drinking, and obesity, with high BMI being a primary reason for the gender disparity in incidence rates\u003csup\u003e[\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]\u003c/sup\u003e. Notably, China has the highest number of GCRC cases and disease burden in the world. China has experienced rapid socioeconomic development and urbanization, accompanied by decreased physical activity levels and the prevalence of Western dietary patterns\u003csup\u003e[\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]\u003c/sup\u003e, making it the country with the highest number of obese individuals\u003csup\u003e[\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]\u003c/sup\u003e, further exacerbating the disease burden. Our study indicates that screening, diagnosis, and intervention processes should be more focused on males.\u003c/p\u003e\u003cp\u003eTo further alleviate the burden of GCRC mortality and DALYs, effective policies should be formulated targeting the risk exposure of the geriatric population to minimize risk factors. This study confirms that a lack of whole grain diet, insufficient milk intake, and high red meat consumption are major dietary risk factors contributing to the GCRC burden. Moreover, these factors interact with a lifestyle lacking physical exercise, such as obesity. Adipose tissue is considered a natural reservoir for macrophages and inflammatory cytokines, and long-term exposure to chronic inflammation in obese individuals is believed to contribute to the development of colorectal cancer\u003csup\u003e[\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]\u003c/sup\u003e. Due to co-occurrence of obesity (requiring prolonged operative time) and muscle atrophy amoung geiatric patients, the risks of both intraoperative bleeding and postoperative infection are significantly elevated\u003csup\u003e[\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e, \u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]\u003c/sup\u003e, further increasing the GCRC burden. This emphasizes the importance of public health interventions aimed at improving dietary habits and lifestyles to reduce the effect of mutiple factors on GCRC risks. Low milk and calcium intake are a major risk factor for CRC mortality in low-income countries. Calcium not only neutralizes bile acids in the intestinal lumen\u003csup\u003e[\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]\u003c/sup\u003e, reducing intestinal permeability and thereby decreasing the absorption of harmful substances\u003csup\u003e[\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e]\u003c/sup\u003e, but also promotes the differentiation of rectal epithelial tissue\u003csup\u003e[\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e]\u003c/sup\u003e, reducing DNA damage in the rectal mucosa\u003csup\u003e[\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e]\u003c/sup\u003e. Addressing the widespread exposure to this risk factor in this region is necessary. In high-income countries, in addition to dietary factors, a lack of physical activity can be classified as a major risk factor for CRC mortality. The association between lack of physical exercise and colorectal cancer has been confirmed by most studies\u003csup\u003e[\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e]\u003c/sup\u003e. Specific preventive policies should be developed to reduce exposure to these risk factors and alleviate the burden of CRC. Possible interventions include increasing whole grain intake, reducing red meat and processed meat consumption, and raising public awareness of the importance of physical exercise through public health education, especially among populations exposed to modifiable factors. Identifying the main risk factors for exposure in specific regions based on gender and regional stratification can promote the formulation of specific policies to reduce exposure to risk factors in those areas.\u003c/p\u003e\u003cp\u003eOur predictive model shows a concerning trend. Using the BAPC model, we predict that the prevalence burden of GCRC will further worsen by 2040, indicating that in the future, GCRC will remain a significant public health issue and challenge. Furthermore, the gender disparity in ASMR and ASDR are becoming increasingly pronounced, with the disease burden for males becoming heavier than for females. In the future, primary and secondary prevention of the disease should be prioritized, and the treatment details in disease guidelines for geriatric colorectal cancer patients, especially male patients, should continue to be refined to generate more clinical evidence and continuously improve care quality. Promoting healthier dietary and exercise habits tailored to different regions and genders is particularly important for alleviating the burden of this disease.\u003c/p\u003e\u003cp\u003eThis study also bears certain limitations. Firstly, since the data in the GBD database come from different countries and regions, the measurement bias and different treatment plans may be inevitable, which would influence the accuracy of the GCRC burden assessment. Second, due to data source constraints, we could not stratify between colon cancer and rectal cancer. Third, considering the physique variation of the geriatric population, this study did not delve into the impact of frailty assessments (such as Hospital Frailty Risk Score (HFRS), the Secondary Care Administrative Records Frailty (SCARF) index, and frailty syndromes (FS)) on CRC burden\u003csup\u003e[\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e]\u003c/sup\u003e, but these factors may have different impacts on CRC disease burden in different countries and regions. However, these limitations do not change the fact that this study gives a thorough look at the CRC burden among geriatric adults, which is valuable for disease control.\u003c/p\u003e"},{"header":"5. Conclusions","content":"\u003cp\u003eIn conclusion, this study reports the burden of global GCRC from 1990 to 2021. Although the ASMR and ASDR for GCRC have shown a declining trend over the past 32 years, the deaths cases and DALYs attributed to GCRC have doubled, along with the increase in ASPR, exhibited the latest trends and burdern of GCRC at the global. Our research emphasizes that among the geriatric population, males bear a greater burden of GCRC compared to females, highlighting the need for greater attention to screening, diagnosis, and treatment for males. Our findings indicate that a lack of whole grain diet, insufficient milk intake, high red meat consumption, and lack of physical exercise are four prominent risk factors contributing to the DALY and mortality burden of global GCRC in 2021. Targeted primary prevention is necessary to alleviate the burden of GCRC, and The findings from this analysis can contribute to the formulation of healthcare policies for policymakers, optimize healthcare resource allocation, while also aiding in the development of more comprehensive GCRC guidelines for geriatric patients.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eThe following abbreviations are used in this manuscript:\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"524\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003eGCRC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 461px;\"\u003e\n \u003cp\u003eGeriatric Colorectal Cancer\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003eSDI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 461px;\"\u003e\n \u003cp\u003eSocio-demographic index\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003eASR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 461px;\"\u003e\n \u003cp\u003eAge-standardized rate\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003eASPR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 461px;\"\u003e\n \u003cp\u003eAge-standardized prevalence rate\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003eASIR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 461px;\"\u003e\n \u003cp\u003eAge-standardized incidence rate\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003eASMR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 461px;\"\u003e\n \u003cp\u003eAge-standardized mortality rate\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003eASDR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 461px;\"\u003e\n \u003cp\u003eAge-standardized DALY rate\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003eDALYs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 461px;\"\u003e\n \u003cp\u003eDisability-adjusted life years\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eSupplementary Materials\u003c/strong\u003e: The following supporting information can be downloaded at: https://www.mdpi.com/article/doi/s1, Table S1: DALYs and death of geriatric colorectal cancer between 1990 and 2021. Table S2: Prevalence of 204 countries and regions.Table S3: Incidence of 204 countries and regions. Table S4: DALYs of 204 countries and regions.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions:\u003c/strong\u003e Y.H.: Conceptualization, Visualization, Formal analysis, Writing\u0026mdash;original draft, Writing\u0026mdash;review and editing. S.W.: Investigation, Checking and modifying the manuscript, Project adminis tration. All authors have read and agreed to the published version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical trial number\u003c/strong\u003e: not applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInstitutional Review Board Statement\u003c/strong\u003e: The study did not require ethical approval.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInformed Consent Statement:\u0026nbsp;\u003c/strong\u003eThis was a retrospective, observational cohort study based on open access GBD database. Therefore, consent was not applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability Statement:\u003c/strong\u003e The datasets used during the current study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of Interest:\u0026nbsp;\u003c/strong\u003eThe authors declare no conflicts of interest.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA. Cancer J. Clin., 2024, 74(3): 229-263.\u003c/li\u003e\n\u003cli\u003eSiegel R L, Miller K D, Goding Sauer A, et al. Colorectal cancer statistics, 2020[J]. CA. Cancer J. Clin., 2020, 70(3): 145-164.\u003c/li\u003e\n\u003cli\u003eLi N, Lu B, Luo C, et al. 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Cancer Res., 2023, 83(6): 906-921.\u003c/li\u003e\n\u003cli\u003eRichardson A, Hayes J, Frampton C, et al. Modifiable lifestyle factors that could reduce the incidence of colorectal cancer in New Zealand[J]. N. Z. Med. J., 2016, 129(1447): 13-20.\u003c/li\u003e\n\u003cli\u003eMartinez A, Hamieh N, Colineaux H, et al. Influence of sex on the incidence of colorectal cancer: considering the influence of gender mechanisms[J]. Soc. Sci. Med. (1982), 2025, 376: 118058.\u003c/li\u003e\n\u003cli\u003eLimsui D, Vierkant R A, Tillmans L S, et al. Postmenopausal hormone therapy and colorectal cancer risk by molecularly defined subtypes among older women[J]. Gut, 2012, 61(9): 1299-1305.\u003c/li\u003e\n\u003cli\u003eSchwingshackl L, Schwedhelm C, Hoffmann G, et al. Food groups and risk of colorectal cancer[J]. Int. J. Cancer, 2018, 142(9): 1748-1758.\u003c/li\u003e\n\u003cli\u003eWang Y, Zhao L, Gao L, et al. Health policy and public health implications of obesity in China[J]. 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The protective effect of supplemental calcium on colonic permeability depends on a calcium phosphate-induced increase in luminal buffering capacity[J]. Br. J. Nutr., 2012, 107(7): 950-956.\u003c/li\u003e\n\u003cli\u003eFedirko V, Bostick R M, Flanders W D, et al. Effects of Vitamin D and Calcium on Proliferation and Differentiation in Normal Colon Mucosa: A Randomized Clinical Trial[J]. Cancer Epidemiol. Biomark. Prev. Publ. Am. Assoc. Cancer Res. Cosponsored Am. Soc. Prev. Oncol., 2009, 18(11): 2933-2941.\u003c/li\u003e\n\u003cli\u003eFedirko V, Bostick R M, Long Q, et al. Effects of Supplemental Vitamin D and Calcium on Oxidative DNA Damage Marker in Normal Colorectal Mucosa: A Randomized Clinical Trial[J].Cancer Epidemiol. Biomark. Prev. Publ. Am. Assoc. Cancer Res. Cosponsored Am. Soc. Prev. Oncol., 2010, 19(1): 280-291.\u003c/li\u003e\n\u003cli\u003eStein M J, Baurecht H, Bohmann P, et al. Diurnal timing of physical activity and risk of colorectal cancer in the UK Biobank[J]. BMC Med., 2024, 22(1): 399.\u003c/li\u003e\n\u003cli\u003eMontroni I, Ugolini G, Saur N M, et al. Predicting Functional Recovery and Quality of Life in Older Patients Undergoing Colorectal Cancer Surgery: Real-World Data From the International GOSAFE Study[J]. J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol., 2023, 41(34): 5247-5262.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Table","content":"\u003cp\u003eTable 1 is available in the Supplementary Files section.\u003c/p\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":"75+year-old cohort, Colorectal cancer, Global Burden of Disease, Prevalence, Incidence, Mortality, Disability-adjusted life years","lastPublishedDoi":"10.21203/rs.3.rs-7297355/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7297355/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eGeriatric patients diagnosed with colorectal cancer (GCRC) face elevated rates of mortality and complications; however, yet current guidelines lack randomized controlled trial (RCT) data specifically for individuals aged 75 and above (75+). Although the burden of colorectal cancer in the global population aged 65 and older has decreased, the trends in 75+ colorectal cancer patients have not been studied. This study assessed the prevalence, incidence, mortality, and Disability-Adjusted Life Years (DALYs) of geriatric colorectal cancer at global and national levels from 1990 to 2021, and projects trajectories to 2045. Using data from the 2021 Global Burden of Disease (GBD) study, we calculated age-standardized rates (ASRs) for 204 countries/regions. Joinpoint regression identified time trends through Average Annual Percentage Changes (AAPCs), while Bayesian Age-Period-Cohort models (BAPC) predicted future burdens. Globally, the burden of colorectal cancer in the population aged 75+ has decreased (AAPC of ASDR: −14.832, 95% UI: −15.179 to -14.485). However, the prevalence has significantly increased, with an average annual increase of 4.491 (95% UI: 4.347-4.635), and a much larger increase in males compared to females (9.313 [95% UI: 9.101-9.526] vs. 0.564 [95% UI: 0.380-0.748]). Major risk factors include a diet lacking whole grains, insufficient milk intake, high red meat consumption, and lack of physical exercise, which are the main causes of mortality and DALYs. Predictions indicate that by 2040, the prevalence of GCRC will increase globally, especially among males (with an expected increase of 44% in prevalence from 1990 to 2040). The burden of disease in the geriatric population aged 75+ is expected to continue to rise, with significant gender differences. Public health efforts should focus on changing dietary structures and increasing physical exercise. This study emphasizes the urgent need for intervention strategies targeting geriatric patients to address the evolving epidemiological challenges in colorectal cancer prevention and control.\u003c/p\u003e","manuscriptTitle":"Evolving landscape of geriatric colorectal cancer: Global and regional burden, risk factor dynamics, and future scenarios (the Global Burden of Disease 1990–2040)","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-12 14:43:55","doi":"10.21203/rs.3.rs-7297355/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":"b356b898-95a5-426b-9fb6-190568f12631","owner":[],"postedDate":"September 12th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-11-05T08:39:08+00:00","versionOfRecord":[],"versionCreatedAt":"2025-09-12 14:43:55","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7297355","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7297355","identity":"rs-7297355","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}