Global, regional, and national burden of colorectal cancer attributable to high BMI, 1990-2021: a systematic analysis for the Global Burden of Disease Study 2021

Yiming Liu¹Hui Cai^1*Yongfeng Wang¹jianfeng ma¹yawen lu¹Ziyuan Ding²

• ¹First Hospital of Lanzhou University, Lanzhou, China
• ²Lanzhou University Second Hospital, Lanzhou, Gansu Province, China

Globally, colorectal cancer ranks as the second leading cause of cancer deaths and the third most diagnosed cancer [1]. In 2020, there were more than 1.90 million new cases of colorectal cancer, which took up 10% of all cases of cancer, and 930,000 deaths from the disease, which accounting for 9.4% of the deaths caused by cancer, according to the Global Burden of Disease Study (GBD) 2020 [2]. In addition to causing patients great physical and psychological suffering, colorectal cancer has major social and financial repercussions. Therefore, the creation of effective prevention and control methods requires extensive study of the pathophysiology and risk factors of colorectal cancer. One of the most significant risk factors for colorectal cancer is a high body mass index (BMI). Numerous studies [3][4][5] have demonstrated a strong correlation between colorectal cancer onset and progression and a high body mass index. The World Health Organization (WHO) defines obesity as a BMI of 30 kg/m². Obesity is closely associated with other chronic diseases, such as diabetes and heart disease, in addition to increasing the risk of colorectal cancer [6]. Epidemiological data suggest that obesity is associated with a 30-70% increased risk of colon cancer in men, while this association is less consistent in women. Visceral fat or abdominal obesity seems to be more worrying than subcutaneous fat obesity, with an additional risk for every 1 kg/m2 increase in BMI [7]. Moreover, high BMI may also lead to chronic inflammation and insulin resistance, factors that further promote the development and development of colorectal cancer [8].Although numerous studies have explored the association of high BMI and colorectal cancer, the specific impact of colorectal cancer burden due to high BMI and its dynamic trends remain poorly studied. In particular, whether there are significant differences in colorectal cancer burden resulting from high BMI between countries and regions globally and what are the reasons for these differences still need to be further explored. Understanding this information is important for the development of precise prevention strategies and resource allocation.Unlike prior GBD studies [9][10][11] focusing on general cancer burden, this analysis specifically quantifies the dynamic trends of high BMI-attributable colorectal cancer across diverse SDI regions, offering novel insights into socioeconomic disparities and gender-specific risk profiles. We now have a better grasp of the relationship between high BMI and colorectal cancer burden, which provides a scientific basis for developing focused prevention strategies. The Global Burden of Disease Study (GBD 2021) data will be specially used in this study to calculate disability-adjusted life years (DALYs), age-standardized death rates (ASMR), age-standardized DALY rates (ASDR), and deaths from high BMI colorectal cancer from 1990 to 2021. These data will be stratified by sex, age, region, and quintiles of the sociodemographic index (SDI).We carried out a secondary analysis for GBD 2021 (https://ghdx.healthdata.org/gbd-results-tool). The GBD 2021 Year includes nationally comparable surveys, census data, and meta-analysis findings in addition to offering an easily accessible epidemiological assessment of colorectal cancer and high BMI covering 21 GBD regions and 204 countries/regions from 1990 to 2021. GBD 2021 The quality and thoroughness of the survey analysis are ensured by using data from many sources, such as peer-reviewed literature, survey data, disease registration, and hospital admission records. The Global Health Data Exchange Network Tool (http://ghdx.healthdata.org/) provides a thorough explanation of various data sources and their validation procedures for systematic evaluation and acquisition.We retrieved the 95% uncertainty intervals (UIs) and ASDR estimates for colorectal cancer from 1990 to 2021 by sex and location. We obtained colorectal cancer fatalities, DALYs, ASMR, and ASDR from 1990 to 2021 using data from the Global Burden of Disease Study 2021. 204 nations and regions were among the subjects, who were categorized by SDI quintiles, sex, age, and geography. We also utilized the SDI, a composite measure of development based on the geometric mean of three factors: per capita income, adult education level over 15, and fertility under 25. 95% uncertainty intervals (UIs) and numerical values were used to present the data. The SDI is a thorough indicator that shows a substantial relationship between economic and developmental levels and health outcomes. It combines per capita income, average educational attainment, and birth rate levels to provide a comprehensive evaluation of the level of development in each region covered in the GBD research. The world is divided into five zones, ranging from lowest to highest: low, low-middle, middle, high-middle, and high SDI regions. The range of the SDI index is 0 to 1.The database is openly accessible and does not include personal data. Therefore, seeking approval from a research ethics committee is not necessary.Colorectal cancer is a type of cancer that originates in the colon or rectum. It is typified by the uncontrolled growth of cells in the lining of the colon or rectum, which can result in the development of tumors and potentially spread throughout the body [9]. A high BMI is usually defined as a BMI of 25 kg/m² or more and is determined by a person's weight in relation to their height. A BMI of 25 to 29.9 is considered overweight, and a BMI of 30 or more is considered obese [12].Detailed descriptions of the GBD 2021 methodology are available in prior publications [14][15]. Specifically, attributable deaths, years of life lost (YLLs), years of life lived with disability (YLDs), and DALYs for high BMI were estimated at the regional level, broken down by country worldwide, using the GBD 2021 study. The BMI for each age, sex, location, and year was determined using all available data sources, including the survey that represented the population and information from surveillance using spatiotemporal Gaussian process regression and Disease Modeling Meta regression (DisMod-MR). DisMod-MR, an integrated system modeling technique, is used in the study to quantify the total amount of deaths by age, gender, country, and year.The association between the burden of colorectal cancer and high BMI was next investigated using a frontier analysis, a quantitative method that determines the lowest rate of age-standardized deaths and DALYs based on development status as indicated by the SDI. The frontier for deaths and DALYs indicates the lowest numbers that any country or region may get based on its SDI. The effective difference is the distance from the frontier; depending on the development stage of the nation or region, a bigger effective difference suggests possible unrealized gains (decreases in colorectal cancer fatalities and DALYs). We created a frontier using SDI for age-adjusted high BMI-related neoplasm deaths and DALYs using data from 1990 to 2021 and the free disposal hull approach for a nonlinear frontier delineation. We employed 100 bootstrapped data samples, chosen at random with replacement from each nation, territory, and year to account for uncertainty.Then, using the bootstrapped samples, we calculated the mean DALYs and neoplasm deaths for each SDI value associated to high BMI. To create a smoothed frontier, we used LOESS regression with a local polynomial degree of 1 and span of 0.2. Super-efficient nations were not included in the frontier generation in order to lessen the impact of outliers. Using 2021 SDI and age-standardized colorectal cancer deaths and DALYs rate data points for each nation or region, we computed the effective difference (the absolute distance from the frontier) in order to understand the relationship between age-standardized colorectal cancer deaths and DALYs rates and the 2021 frontier. A zero-distance score was assigned to nations or territories that have fewer fatalities and DALYs than the region's borders.The number of fatalities within a given population within a certain time period was used to diagnose deaths. Similar to health state, YLDs were computed using standardized disability weights. Additionally, YLLs were computed using the maximum observed life expectancy as a reference. They were then added up to determine DALYs. The exposure amount, theoretical minimal risk level, and estimations of relative risk were used to calculate PAFs (population attributable fractions). PAFs of BMI outcome pair split by year, gender, and age were estimated using a comparative evaluation approach for risk [16]. The number of deaths and DALYs attributable to high BMI was estimated by multiplying the PAFs by the number of colorectal cancer-related deaths and DALYs.The following is the definition of the PAF equation:= =1 ()() -1 =1 ()()where P (x) is the proportion of the target population exposed to high BMI at level x, and RR (x) is the relative risk of high BMI level x.Data on mortality, DALYs, ASMR, and ASDR were presented as figures with 95% UIs due to the 2.5th and 97.5th percentiles of the aforementioned 1000 estimations. Age was broken down into sixteen four-year chunks. The regression equation, where x is the year, was used to fit the ASR. Therefore, using the model and its 95% CI, ASR, including ASMR and ASDR, was regarded as growing if the lower limit of the 95% CI of the projected annual percentage change (EAPC) computation was greater than zero. Conversely, the ASR displayed a declining trend if the upper limit of the 95% CI of the EAPC was less than zero. If the 95% CI included 0, the ASR was considered stable. Smoothing spline models were established using the correlation between the SDI and the EACP in ASMR or ASDR of colorectal cancer, which is associated with elevated sodium intake in 33 locations. The EAPC, an indicator that represents the trends of age-standardized rates (ASR) within a certain time period, was utilized to examine the longitudinal trends of the ASMR and ASDR of colorectal cancer linked to high salt intake from 1990 to 2019.The driving forces and prospects for improvement were also evaluated using decomposition and frontier analysis. In this study, we employed the Spearman rank test to examine the correlations between the 1990 ASMR or ASDR and the 2021 SDI. All statistical analysis was conducted using R program (version 4.1.2). A significant two-sided p-value was defined as less than 0.05.As the prevalence of obesity rises globally, especially in low-and middle-income countries, so does the number of colon cancer deaths and DALYs caused by high BMI. In 2021, high BMI was projected to cause 99,267.99 (95% UI 42,956.34, 157,948.81) colorectal cancer deaths and 2,364,664.16 (95% UI 1,021,593.57, 3,752,340.44) DALYs globally. large-income countries had a large number of fatalities and DALYs, but their growth rates were comparatively stable; low-and middle-income countries had low numbers of deaths and DALYs, but they were still growing. The anticipated figures for high-income individuals were 796131.89 (95 % UI 346991.56,1260128.77) and 38393.55 (95 % UI 16340.91,61301.29). (Table 1 and2). In 1990 -2021, the number of these indicators increased faster among men and faced a higher health burden. This suggests that men are more severe in health loss of colorectal cancer triggered by high BMI than women. (Table 1 and 2). Males' high BMI-attributed ASMR for colorectal cancer increased from 1.17 (95% UI: 0.49,1.90) in 1990 to 1.33 (95% UI: 0.57,2.13) in 2021, whereas females' ASMR decreased from 1.11 (95% UI: 0.48,1.81) per every 100,000 people in 1990 to 1.04 (95% UI: 0.45,1.65) in 2021. The ASDR decreased from 24.73 (95% UI: 10.60,39.99) per 100,000 population in 1990 to 23 Interestingly, global colorectal cancer-related ASMR increased slightly, which significantly increased in low-and middle-income areas and decreased in high-income areas. Global EAPC was 3.00%(95%CI: -3.43%,10.69%), and EAPC in high-income regions was -13.91%(95%CI: -18.98%,-7 .96%), respectively. Interestingly, global colorectal cancer-related ASDR increased slightly, which significantly increased in low-and middle-income areas and decreased in high-income areas. Global EAPC was 7.02%(95%CI: -0.08%,16.07%), and EAPC in high-income regions was -10.45%(95%CI: -15.91%,-4.35%).For both males and females, age-specific mortality and DALYs for colorectal cancer caused by high BMI rose with age (ptrend < 0.05). In 2021, the greatest number of colorectal cancer fatalities in both sexes that were linked to high BMI occurred in the 70-74 age range (Figure 1A). In the 65-69 age group, the DALYs associated with colorectal cancer peaked in both sexes, and these trends were comparable (Figure 1B). People between the ages of 65 and 74 accounted for the bulk of fatalities and DALYs. Furthermore, more deaths and DALYs occurred in the 20-79 age group for males than for females, while more deaths and DALYs occurred in the 80+ age group for females than for males (Figure 1A,B). The number of deaths from colorectal cancer and the DALYs (due to high BMI) showed an increasing trend (ptrend <0.05). The colorectal cancer deaths in both sexes increase with the years and reached a new peak in 2021 (Figure 1C). The number of DALYs associated with colorectal cancer at different periods, also showing an increasing trend year by year and reaching a new high point in 2021 (Figure 1D). These plots indicate that the number of colorectal cancer deaths and DALYs from high BMI gradually increased over time in both males and all ages (Figures 1C,D). There is significant geographical variation in the spatial distribution of ASMR and ASDR linked to high BMI in 2021. Southern Latin America, Greenland, the Balkan Peninsula, Northern Europe, and North Asia are the primary regions where high ASMRs are found. On the other hand, areas like the Caribbean and Central America, the Persian Gulf, Southeast Asia, West Africa, and the Eastern Mediterranean have lower ASMRs (Figure 2A,B). EAPC in colorectal cancer ASMR and ASDR attributed to high BMI from 1990 to 2021 , there is a conspicuous increase in regions such as Caribbean and central America, Persian Gulf, Southeast Asia and West Africa, contrasting with a significant decrease in Balkan Peninsula, Eastern Mediterranean, Northern Europe and Central AsiaNorth (Figure 2C,D As SDI increases, both age-standardized death rate and age-standardized DALY rates show a general decreasing trend. Most middle-to-high SDI countries, such as the United States, the United Kingdom, and Germany, exhibit a downward trend in both mortality and DALY rates; however, low SDI countries, such as Nigeria and Malawi, show varying trends. As SDI increases, the age-standardized DALY rate generally decreases (Figures 3A,B). The data points for each year gradually shift to the lower right over time, indicating a general decline in both mortality and DALY rates in countries with varying SDI levels (Figures 3C,D). A comprehensive analysis reveals that high BMI significantly increases the burden of colorectal cancer, particularly in middle-to-high SDI countries.BMI Based on data from 1990 to 2021, the relationship between ASMR and ASDR) due to colorectal cancer attributable to high BMI and the SDI shows a clear positive correlation across both regions and countries. Specifically, in high SDI regions, ASMR and ASDR increase as SDI rises, but may decline once a certain SDI threshold is reached, indicating a non-linear relationship between SDI and colorectal cancer burden. On the other hand, ASMR and ASDR show a steady and positive association, rising progressively with increasing SDI in low SDI regions. There is a link between ASDR connected to colorectal cancer (R=0.74, p＜0.001) and high BMI and SDI in 22 regions (figure 4A,B). In 204 nations, there was a link between high BMI and SDI and colorectal cancer-related ASMR (R=0.68, p＜0.001) and ASDR (R=0.65, p＜0.001) (figure 4C,D). However, these results imply that areas with greater SDI typically have a higher burden of colorectal cancer due to high BMI.Regional analyses highlight that in high-income areas (e.g., North America and Western Europe), the colorectal cancer burden initially rises with increasing SDI but starts to decrease once a peak is reached, with estimates aligning closely with expected values. In middle-income regions (e.g., East Asia and Latin America), both ASMR and ASDR increase significantly with SDI, with estimates slightly above expected levels. In contrast, in low-income regions (e.g., Sub-Saharan Africa), the increase in ASMR and ASDR is less pronounced, and the burden remains lower than expected. Colorectal cancer death rate due to high BMI was significantly increased globally between 1990 and 2021. The death rate in colorectal cancer usually decreases with increasing SDI, with the inequality index slope decreasing from-2.16 in 1990 to-0.96 in 2021 (Figure 5A). Similarly, the slope of the inequality index for DALY rates decreased from -28.10 in 1990 to -46.86 in 2021 (Figure 5C). Death rate and cumulative DALY distribution were more concentrated in high SDI countries. The death concentration index increased from 0.367 in 1990 to 0.396 in 2021. The DALY concentration index increased from 0.374 in 1990 to 0.397 in 2021 (Figure 5B,D). Among them, China has a large proportion of the total population, but the proportion of death rate and DALY distribution increased significantly from 1990 to 2021, both reaching nearly 0.25 (25%), indicating the increasing impact and burden of high BMI on colorectal cancer, while India has the opposite effect. High BMI has emerged as a major global health concern as a result of the growth of the national economy and the improvement of living conditions. The GBD 2021 found that high SDI countries had a declining colorectal cancer death rate and DALY of colorectal cancer, primarily as a result of improved medical conditions and control measures [17]. However, the burden of colorectal cancer is still increasing in some high-SDI countries (e. g., the US and the UK), suggesting that more effective intervention strategies may be needed in these countries. Obesity persists in these nations, often linked to poor diet, sedentary lifestyles, and inadequate early detection [14,18]. In low-and middle-income nations, where the public health system is comparatively poor and the prevention and treatment of obesity-related disorders have not received enough attention, the burden of colorectal cancer caused by high BMI rises annually [19][20]. For low-and middle-income countries, tailored interventions such as subsidized community-based obesity prevention programs (e.g., promoting affordable healthy diets), nationwide salt reduction campaigns, and mobile screening units for rural areas should be prioritized. For high-SDI countries, policies [21] targeting processed food taxation and workplace wellness initiatives may enhance compliance with dietary guidelines.According to our research, the number of colorectal cancer deaths and DALYs attributable to high BMI increased by more than three times in 2021, reaching 99.26 thousand and 2364.66 thousand, respectively. Based on 204 countries and 21 regions, our study examined the risk-attributable illness burden worldwide over a 31-year longitudinal period. The study may offer insightful information for low-cost colorectal cancer prevention as well as important scientific and theoretical support.Many studies [22][23][24][25] have shown that obesity is a risk factor for colorectal cancer, which is related to age and gender, and has been trending younger in recent years. We discovered that the 20-79 age range had greater age-specific mortality and DALY rates for colorectal cancer due to high BMI than did women, while the inverse was true for those over 80. In the 20-79 years, colorectal cancer ASMR and DALY from high BMI were closely related to a variety of biological and social behavioral factors. First, there were significant differences [26] in fat distribution, metabolic rate and hormone levels between men and women, especially since the effect of high BMI on colorectal cancer was closely related to gender-specific hormone levels. This is consistent with the findings of Lin et al. [27], who demonstrated that the ratio of estradiol to testosterone was associated with colorectal cancer risk in women. Postmenopausal women have lower estrogen levels and lose their protective effects, leading to an increased risk of colorectal cancer. Compared with premenopausal women, men are more likely to accumulate visceral fat in the abdomen [28]. The visceral fat area is positively correlated with the prevalence of colorectal cancer [29], leading to a higher risk of colorectal cancer in men aged 20-79. Second, social behavioral factors also play an important role in gender differencesResearch indicates that staying active can lower your chances of getting colon and rectal cancer . Specifically, moderate exercise seems to cut the risk of rectal cancer in both men and women, with the odds dropping to about 70% and 51% respectively [30], compared to those who are less active. The findings suggest the importance of emphasizing testing for estrogen levels, reducing obesity rates and sticking to a healthy lifestyle in preventing colorectal cancer.Our study revealed substantial disparities in ASMR and ASDR for high BMI across regions from 1990 to 2021. The burden of colorectal cancer in the Caribbean and Central America, southeast Asia and other regions increased significantly between 1990 and 2021. This trend may be closely related to the rapid economic growth, urbanization process, and changes in dietary structure in these regions. With the spread of Western dietary patterns, increased intake of meat consumption, especially processed meat products, may exacerbate the colorectal cancer risk, associated with obesity and high BMI [32]. Moreover, lifestyle changes such as reduced physical activity and an increase in dietary high-fat, high-sugar foods [33] may also be important reasons for the rising burden of colorectal cancer in these areas. Similar trends in West Africa may also be associated with lifestyle shifts, urbanisation, and increased associated health risks. Instead, regions including the Balkans, Eastern Mediterranean, Northern Europe and Northern Central Asia showed significant downward trends, with a reduction in the burden of high BMI associated with colorectal cancer. This may be related to the efforts in public health policy, health education and dietary improvement in these regions. For example, the Nordic countries have made remarkable progress in recent years in promoting healthy diet and increasing physical activity [34]. Additionally, these regions have enough medical resources to assist early identification and treatment, which lessens the burden of high BMI-related colorectal cancer.This study explored the effect of high BMI on colorectal cancer burden by analyzing mortality and DALY data between 1990 and 2021, and analyzed the differences in different SDI regions. The results showed that the mortality and DALY rates of colorectal cancer generally decreased with increasing SDI, especially in middle and high SDI countries such as the United States, the United Kingdom and Germany. High SDI areas can effectively implement public health policies and promote healthy diet and lifestyle, thus reducing colorectal cancer burden. Specific reasons include more sophisticated health management systems, extensive early screening, and obesity prevention measures [35]. The latest developments in diagnostic tech, especially with deep learning algorithms, are showing a lot of potential for boosting the detection of colorectal cancer.Studies [36] point out that these advanced learning models can supercharge the accuracy and speed of analyzing pathology images for CRC categorization. At present, deep learning has been widely used in colon cancer endoscopy, histology, medical imaging and screening serological tests. This could lead to earlier diagnoses and improved management of CRC, which might help lighten the load of the disease in the future. Although this wasn't the main focus of our research, integrating these cutting-edge technologies into regular care might just complement traditional prevention methods, particularly in areas with high socioeconomic status where tech is more accessible. However, in low SDI countries, such as Nigeria and Malawi, the burden of colorectal cancer increases due to lack of effective prevention, screening and treatment measures, and mortality and DALY rates are increasing in some countries. This is closely related to the weak public health infrastructure and the lack of health resources in poor areas. Despite the overall downward trend in high SDI countries, some countries such as Germany and the UK still face challenges such as rising obesity rates, unhealthy lifestyle and aging [37].The SDI was found to be a significant factor influencing both the death and DALY rate of disease, making it a novel method of evaluating socioeconomic status [38]. We found that the colorectal cancer burden caused by high BMI showed significant differences and health inequalities in different SDI regions. The burden of colorectal cancer in high-income nations (e.g., North America and Western Europe) is directly tied to the growth in obesity rates, particularly in lifestyle and dietary habits, with obesity emerging as an independent risk factor. However, with the implementation of health policies (e. g., Mexican sugar tax [38] , Scandinavian school nutrition programs [39]), the burden in these countries was effectively controlled. Relatively, the burden of colorectal cancer in middle-income countries (e. g., East Asia and Latin America) continues to grow, mainly due to diet Westernization and obesity prevalence, but public health measures are not widespread, resulting in limited screening and treatment effect s [41]. The burden of gastric cancer associated with high BMI in less developed areas was significantly higher than that in developed areas, with an growing gap between 1990-2021. Enhancing healthcare in low-and middle-income countries requires specific strategies like cost-effective screening and community-based efforts [42]. Future progress in global colorectal cancer care hinges on telemedicine, AI, and mobile health for expanded access and personalized treatment. International collaboration and infrastructure investment are vital for decreasing mortality in resource-poor areas. In recent years, the average BMI in Chinese has been rising [43], which lead to a significant increase in ASMR and ASDR in colorectal cancer due to high energy. A BMI reduction in China remains urgent in China, especially in areas with high BMI, and joint efforts are needed to reduce the intake of excess nutrition in all populations.This study first offers a thorough understanding of the impact of high BMI on the incidence of colorectal cancer by utilizing data from 204 nations and 22 regions worldwide, spanning 31 years of longitudinal data from 1990 to 2021, and exposing its changing trends over time. Second, based on a thorough analysis of the disparities in sex, age, and geographic distribution, the study suggested more detailed and comprehensive prevention strategies for the future. These findings have significant reference value for public health policy, particularly when it comes to offering low-cost prevention recommendations for low-income nations. However, there are a few restrictions to take into account. First, although the relevant information is widely accessible, there hasn't been a comprehensive assessment of how obesity contributes to the disease load across different countries. The reliance on self-reported BMI can lead to measurement bias, especially in areas where health literacy is low. Additionally, inconsistencies in data quality, like the patchy cancer registries in sub-Saharan Africa, might skew the accuracy of the burden estimates even more. Second, our study's data restrictions prevented a thorough analysis of the sex hormones and fat distribution, and they were unable to verify their statistical significance. Third, we only included people who were 20 years of age or older in our study, and there is no pertinent data on groups that are 20 years of age or younger. Fourth, the SDI does not capture cultural preferences or policy implementation gaps and cannot fully reflect healthcare capacity. Furthermore, the conventional BMI thresholds used to identify high-risk populations may not accurately reflect health risks across all demographic groups-particularly among Asian communities or other populations with unique susceptibility factors-potentially skewing research outcomes. Crucially, the connection between elevated BMI and gastric cancer remains understudied in key areas, including tumor localization and histological characteristics. With shifting global dietary patterns driven by economic development, chronic overconsumption has become widespread [44], suggesting nutritional transitions may play a pivotal role in the BMI-gastric cancer association. While these limitations exist, our study offers valuable insights for clinical practice and public health initiatives, paving the way for more targeted investigations.This study confirms high BMI as a major risk factor for colorectal cancer. Despite declining age-standardized rates, global deaths and DALYs remained substantial in 2021. Weight reduction remains pivotal, yet context-specific strategies are essential. Interventions successful in high-SDI countries (e.g., advanced screening technologies) may not be directly transferable to low-SDI settings due to infrastructural constraints. Context-specific strategies-such as leveraging mobile health platforms for education in resource-limited regions-are critical to bridging this gap.