Global burden of colon and rectal cancer and attributable risk factors in 204 countries and territories from 1990 to 2021

Abstract

Objective

Colon and rectal cancers (CRCs) are among the most common malignancies worldwide. While previous studies have examined the disease burden and risk factors of CRC at regional levels, they lack the granularity needed for country-specific policy development. Using updated data from the Global Burden of Disease (GBD) 2021 study, this research explores the national-level spatial distribution of CRC burdens linked to key risk factors and analyzes temporal trends in their contributions. The findings aim to support the formulation of precise public health policies to effectively reduce CRC incidence.

Methods

Based on data from the GBD study 2021, we examined CRC-related incidence, prevalence, mortality, disability-adjusted life years (DALYs), and associated risk factors. Age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), and DALY rate (ASDR) were obtained and analyzed from 1990 to 2021. We used regression analysis and stratification across the four World Bank regions to assess geographical variations and the effect of economic development levels. We further assessed the contribution of various risk factors to CRC-related deaths and DALYs, while analyzing the distribution and temporal trends of the top three contributing risk factors.

Results

On a global scale, the ASDR for CRC declined from 357.33 per 100,000 in 1990 to 283.24 per 100,000 in 2021 (95% confidence interval [CI]: -0.82 to -0.64). In 2021, the regions classified by the World Bank as high income exhibited the highest ASDR in 2021, at 347.35 per 100,000, while the lower-middle-income regions reported the lowest ASDR, at 179.48 per 100,000. During this period, the global ASMR fell from 15.56 to 12.40 per 100,000, while the ASIR rose from 24.04 to 25.60 per 100,000. However, these trends were not consistent across different World Bank income regions. Key risk factors contributing to CRC included high red meat consumption, obesity, insufficient calcium intake, and alcohol consumption, with variations observed among the World Bank income groups.

Conclusion

Although the global burden of colorectal cancer (CRC) has declined from 1990 to 2021, particularly in high-income regions, the incidence rate continues to rise. The increase is more pronounced among individuals aged 50 years and older, who also bear a higher absolute incidence than younger populations. High red meat consumption, high body mass index (BMI), and low calcium intake remain the leading global risk factors for CRC. Effective weight management and the promotion of healthy lifestyles are essential strategies for reducing CRC risk across sexes, while smoking and alcohol control are particularly critical for alleviating the burden among males.

Introduction

Colon and rectal cancers (CRCs) originate in the colon or rectum owing to the irregular proliferation of glandular epithelial cells within these regions. CRC is primarily categorized into three types: sporadic, hereditary, and those associated with colitis. Recent data from GLOBOCAN indicate that in 2020, there were over 1.9 million new diagnoses of CRC globally, resulting in more than 930,000 fatalities, making CRC the third most prevalent cancer and the second leading cause of cancer-related mortality worldwide [1]. CRC is a malignancy closely associated with lifestyle, dietary, and genetic factors [2]. Its diagnosis typically involves a full colonoscopy combined with biopsy, and a digital rectal examination is essential [3]. With advancements in surgical equipment and operative techniques, surgical treatment for CRC has undergone tremendous changes. Laparoscopic technology has largely replaced open surgeries, becoming the standard method for treating CRC. Similar to other cancers, the surgical treatment outcomes for CRC are evaluated based on the 5-year postoperative survival rate.

Previous studies [4,5,6] have primarily focused on describing the current status and temporal trends of the disease burden of CRC, as well as the proportion of CRC burden attributable to related risk factors at the regional levels. However, such studies lack the granularity needed to formulate tailored policies for specific countries. To address this gap and provide a more solid foundation for developing targeted policies to more effectively reduce CRC incidence, with the recently updated GBD 2021 data, this study further presents the spatial distribution of the CRC disease burden attributable to the main risk factors at the national level and analyzes the temporal trends in the contribution of these key risk factors to the CRC burden, which will assist in the precise formulation of public health policies and achieve the intended objectives.

The GBD study provides a comprehensive framework for assessing the effect of CRC across different regions and periods [7]. Relying on this database, this study aimed to investigate how geographic location, level of economic development, age, and sex influence global trends in CRC incidence, prevalence, mortality, and disability-adjusted life years (DALYs), utilizing GBD data spanning 204 countries and territories from 1990 to 2021.

Methods

Data sources and disease definition

This study using data derived from the Global Burden of Disease (GBD) study, accessible via the Global Health Data Exchange platform (https://vizhub.healthdata.org/gbd-results/). The GBD study integrates extensive epidemiological information from 204 countries and territories, covering 369 diseases and conditions alongside 88 risk factors. Detailed methodologies for data collection, processing, and analysis within GBD 2021 have been extensively documented in prior publications [8, 9]. For this study, annual data on CRC incidence, mortality, and DALYs, as well as their age-standardized rates (ASRs), were extracted from the GBD 2021 dataset, spanning the period from 1990 to 2021. CRC cases were identified based on ICD-10 codes C18, C19, and C20. Estimates for CRC prevalence, incidence, and DALYs, including their 95% uncertainty intervals (UIs), were obtained using GBD 2021 methods. DALYs were calculated as the sum of years lived with disability and years of life lost (Supplementary Methods).

The Institutional Review Board at the University of Washington exempted this study from the requirement for informed consent for GBD-related research. The study adhered to the STROCSS reporting guidelines [10].

Gross national income per capita

To classify countries based on their economic development levels, this study used the World Bank’s categorization of nations into four income groups, determined by gross national income (GNI) per capita. These groups include low-income economies (GNI per capita ≤ $1,135), lower-middle-income economies ($1,136–$4,465), upper-middle-income economies ($4,466–$13,845), and high-income economies (GNI per capita ≥$13,846). Regarding the use of the World Bank’s income categorizations, we used the results extracted for World Bank income levels from GBD data. Regarding the use of the World Bank’s income categorizations, we used the results extracted for World Bank income levels from GBD data.

Risk factors

Numerous studies provide strong evidence linking specific risk factors to CRC. These include smoking, alcohol consumption, elevated body mass index (BMI), high fasting plasma glucose, insufficient physical activity, and diets rich in red and processed meats but low in calcium and fiber [3, 4]. The proportion of deaths and DALYs attributable to each risk factor was assessed using the GBD results tool, which follows risk factor definitions that have been established in earlier studies [4].

Statistical analysis

A comprehensive analysis evaluated the national burden of CRC, incorporating and excluding risk factors, with assessments focused on incidence, prevalence, mortality, and DALYs. The study examined how economic development levels affected CRC burden while analyzing its distribution by sex and age group. Temporal trends in CRC incidence, mortality, and DALYs were described using ASRs and average annual percent changes (AAPCs). Trends in risk factor contributions were also assessed over time.

The ASR was calculated per 100,000 individuals using the following formula:

$$\:ASR=\frac{{\sum\:}_{i=1}^{A}{a}_{i}{w}_{i}}{{\sum\:}_{i=1}^{A}{w}_{i}}\times\:\text{100,00}$$

α_i: the age-specific rate for the i-th age group;

w_i: the number of people in the corresponding i-th age group among the standard population;

A: the number of age groups.

Temporal trends from 1990 to 2021 were analyzed using JoinPoint software (version 5.2.0), applying a log-linear regression model to estimate the annual percent change and AAPC. Statistical significance was determined at a two-sided α = 0.05, with percentage changes considered significant if the 95% UI excluded zero. Data analysis and visualization were performed using R (version 4.1.1), JoinPoint (version 5.2.0), and Adobe Illustrator (version 23.0.3).

Results

Global level

In 2021, CRC affected approximately 11.679 million individuals globally, corresponding to an age-standardized prevalence rate of 134.8 per 100,000, a 24.6% increase compared to 1990. During the same year, CRC was responsible for 1.04 million deaths worldwide, with an ASMR of 12.4 per 100,000, a 20.3% reduction since 1990. Further, the global CRC-related burden, measured in DALYs, reached 24.4 million in 2021. The associated ASDR was 283.2 per 100,000, reflecting a decline of 20.7% over the 31-year period (Table S1).

Regional level

In 2021, the highest ASMRs for CRC were observed in Central Europe (22.6 per 100,000), Southern Latin America (18.1 per 100,000), and Eastern Europe (18.1 per 100,000). Conversely, the lowest ASMRs were reported in high-income South Asia (4.6 per 100,000), Oceania (5.6 per 100,000), and Western Sub-Saharan Africa (6 per 100,000).

Similarly, the highest age-standardized DALY rates were recorded in Central Europe (506.5 per 100,000), Eastern Europe (424.5 per 100,000), and Southern Latin America (408 per 100,000). Regions with the lowest DALY rates included South Asia (120.4 per 100,000), Western Sub-Saharan Africa (132.1 per 100,000), and Central Sub-Saharan Africa (177.8 per 100,000).

From 1990 to 2021, the largest increases in the age-standardized point prevalence of CRC were observed in Central Latin America (148.8%), East Asia (140.1%), and Andean Latin America (111.2%). In contrast, significant decreases were observed in high-income North America (− 9.6%) and Central Asia (− 8.8%).

During the same period, Australasia experienced the largest decline in CRC-related ASMRs at 41.2%, followed by high-income North America with a 37.1% reduction, and Western Europe with a 34.2% decrease. The most significant reductions in age-standardized DALY rates were observed in Australasia (43.4%), Western Europe (34.4%), high-income North America (32.7%), and Central Asia (30%) (Fig. 1, Table S1).

Fig. 1

Percentage change in ASRs of prevalence, mortality, and DALYs globally and across 21 regions. Legend: percentage change in ASRs of age-standardized prevalence, age-standardized mortality, age-standardized DALYs in globe and 21 regions. DALYs, disability-adjusted life years

National level

In 2021, the ASIR of CRC ranged from 3.3 to 69.8 cases per 100,000 globally. The highest ASIRs were reported in the Kingdom of the Netherlands (69.8), the Principality of Monaco (68.3), and Bermuda (61.8), while the lowest rates were observed in the Republic of Gambia (3.3), the Independent State of Papua New Guinea (3.9), and the Republic of Mozambique (4.1).

Similarly, the ASMRs for CRC in 2021 varied between 3.6 and 27.5 deaths per 100,000. The Eastern Republic of Uruguay (27.5), Hungary (26.0), and Bulgaria (25.7) recorded the highest ASMRs, whereas the lowest rates were observed in the Republic of Gambia (3.0), the Independent State of Papua New Guinea (3.6), and the People’s Republic of Bangladesh (3.6).

In terms of ASDRs, CRC burden in 2021 ranged from 70.7 to 615.0 per 100,000 population. Hungary (615.0), Bulgaria (605.0), and the Eastern Republic of Uruguay (598.8) exhibited the highest DALY rates, whereas the lowest rates were recorded in the Republic of Gambia (70.7), the Sultanate of Oman (81.0), and Mozambique (86.4) (Fig. 2).

Fig. 2

Age-standardized CRC incidence, mortality, and DALYs for both sexes in 204 countries and territories, 2021. Legend: age-standardized CRC incidence (A), mortality (B), and DALYs (C) for both sexes in 204 countries and territories in 2021. DALYs, disability-adjusted life years; CRC, colon and rectum cancer

Temporal trends of CRC by world bank income regions

Globally, the ASDR for CRC declined from 357.33 per 100,000 in 1990 to 283.24 per 100,000 in 2021. The AAPC was − 0.73 (95% CI: -0.82 to -0.64), reflecting a significant downward trend. Across the four World Bank income groups, the ASDR for CRC showed reductions, with high-income regions experiencing the most substantial decrease in ASDR compared to 1990 (a 1.4-fold reduction, AAPC: -1.13; 95% CI: -1.23 to -1.04).

In 2021, the ASDR was highest in high-income countries (347.35 per 100,000; 95% UI: 325.77 to 362.59) and lowest in lower middle-income regions (179.48 per 100,000; 95% UI: 164.36 to 195.46). Despite high-income regions showing the greatest decline over the study period, their ASDR remained consistently higher than other income groups throughout 1990–2021 (Fig. 3).

Fig. 3

Trends in ASIR, ASMR, and ASDR of CRC from 1990 to 2021. Legend: Trends in ASIR, ASMR, and ASDR of CRC from 1990 to 2021. ASIR, age-standardized incidence rate; ASMR, age-standardized mortality rate; ASDR, age-standardized DALYs (disability-adjusted life years) rate; CRC, colon and rectum cancer

Temporal trends of CRC by sex

Among males, the age-standardized DALY rate showed a varied downward trend over time. A non-significant slight increase was observed from 1990 to 1994 (APC: 0.05; 95% CI: −0.17 to 0.27; P = 0.634). This was followed by a significant decrease from 1994 to 1997 (APC: −0.91; 95% CI: −1.46 to − 0.35; P = 0.004), and a continuing decline from 1997 to 2004 (APC: −0.30; 95% CI: −0.38 to − 0.21; P < 0.001). A sharper drop occurred between 2004 and 2007 (APC: −1.27; 95% CI: −1.74 to − 0.80; P < 0.001). Although the rate stabilized slightly from 2007 to 2011 (APC: −0.23; 95% CI: −0.49 to 0.03; P = 0.073), significant declines resumed in 2011–2014 (APC: −0.78; 95% CI: −1.41 to − 0.14; P = 0.021) and 2014–2021 (APC: −0.37; 95% CI: −0.49 to − 0.24; P < 0.001).

For females, a consistent and significant reduction in ASDR was observed across all time segments. From 1990 to 1994, the APC was − 0.61 (95% CI: −0.94 to − 0.27; P = 0.001), followed by a steeper decline from 1994 to 2003 (APC: −1.23; 95% CI: −1.32 to − 1.14; P < 0.001). This downward trend persisted from 2003 to 2007 (APC: −1.88; 95% CI: −2.30 to − 1.45; P < 0.001), 2007 to 2013 (APC: −1.38; 95% CI: −1.57 to − 1.19; P < 0.001), and 2013 to 2021 (APC: −0.60; 95% CI: −0.72 to − 0.47; P < 0.001) (Fig. 4A).

Fig. 4

Temporal trends of CRC ASDR, ASMR, and ASIR by sex from 1990 to 2021. Legend: temporal trends in age-standardized disability-adjusted life year rate (ASDR), mortality rate (ASMR), and incidence rate (ASIR) of colorectal cancer (CRC) from 1990 to 2021, stratified by sex. The trends illustrate differences in CRC burden between males and females over time

In males, the age-standardized mortality rate showed a predominantly decreasing trend. A non-significant decline was observed from 1990 to 1994 (APC: −0.06; 95% CI: −0.29 to 0.17; P = 0.600), followed by a significant drop from 1994 to 1997 (APC: −0.72; 95% CI: −1.35 to − 0.09; P = 0.028). The decreasing trend persisted from 1997 to 2004 (APC: −0.24; 95% CI: −0.34 to − 0.15; P < 0.001) and became more pronounced between 2004 and 2007 (APC: −1.17; 95% CI: −1.72 to − 0.62; P < 0.001). From 2007 to 2021, the decline continued steadily (APC: −0.45; 95% CI: −0.49 to − 0.41; P < 0.001).

Among females, a consistent and significant decline in ASMR was observed throughout most of the study period. From 1990 to 1994, the APC was − 0.51 (95% CI: −0.77 to − 0.25; P < 0.001), followed by a more substantial drop from 1994 to 2003 (APC: −1.11; 95% CI: −1.20 to − 1.03; P < 0.001). The downward trend continued from 2003 to 2007 (APC: −1.77; 95% CI: −2.17 to − 1.37; P < 0.001) and from 2007 to 2014 (APC: −1.32; 95% CI: −1.46 to − 1.17; P < 0.001). Although the decline slowed between 2014 and 2018 (APC: −0.46; 95% CI: −0.95 to 0.03; P = 0.063), a significant decrease resumed from 2018 to 2021 (APC: −0.98; 95% CI: −1.55 to − 0.41; P = 0.002) (Fig. 4B).

In contrast, the incidence rate among males exhibited a continuous and statistically significant upward trend across all segments. From 1990 to 1996, the APC was 1.10 (95% CI: 0.99 to 1.21; P < 0.001), followed by 0.30 (95% CI: 0.18 to 0.43; P < 0.001) from 1996 to 2002. A further increase occurred between 2002 and 2010 (APC: 0.69; 95% CI: 0.61 to 0.78; P < 0.001), and the upward trend persisted from 2010 to 2021, though at a slower rate (APC: 0.19; 95% CI: 0.12 to 0.26; P < 0.001).

Among females, a significant increase in the age-standardized incidence rate was observed from 1990 to 1995 (APC: 0.61; 95% CI: 0.45 to 0.77; P < 0.001). This was followed by a non-significant downward trend from 1995 to 1999 (APC: −0.30; 95% CI: −0.64 to 0.05; P = 0.085) and from 1999 to 2002 (APC: −0.68; 95% CI: −1.37 to 0.02; P = 0.055). Between 2002 and 2008, a slight but significant decrease was noted (APC: −0.19; 95% CI: −0.35 to − 0.03; P = 0.025), followed by a more pronounced decline from 2008 to 2014 (APC: −0.65; 95% CI: −0.83 to − 0.47; P < 0.001). A non-significant increase occurred between 2014 and 2018 (APC: 0.09; 95% CI: −0.36 to 0.54; P = 0.664), followed by another non-significant decrease from 2018 to 2021 (APC: −0.37; 95% CI: −0.93 to 0.18; P = 0.167) (Fig. 4C).

Temporal trends of CRC by age group

Across all age groups, the incidence of colorectal cancer showed a rising trend over the study period. In the 15–49 years group, the incidence rate increased from approximately 3.96 per 100,000 in 1990 (95% UI: 3.69–4.21) to 5.37 per 100,000 in 2021 (95% UI: 4.91–5.86), indicating a growing burden among younger populations. In the 50–69 years group, incidence rates remained high throughout the period, with a steady increase from approximately 60 per 100,000 in 1990 to over 65 per 100,000 in 2021, reflecting the accumulation of risk with age. Among individuals aged 70 years and older, the incidence rate was the highest, increasing from 198.2 per 100,000 in 1990 (95% UI: 182.3–206.8) to 210.7 per 100,000 in 2021 (95% UI: 187.9–227.1), although the rate plateaued in the later years.

Mortality rates demonstrated a different pattern compared to incidence. In the 15–49 years age group, the mortality rate was low throughout the period and showed a slight downward trend, from 2.19 per 100,000 in 1990 (95% UI: 2.01–2.36) with minimal change over time. In the 50–69 years and 70 + years groups, mortality rates were substantially higher but exhibited a gradual decline, particularly after the early 2000s (Fig. 5).

Fig. 5

Temporal trends of CRC incidence and mortality rates by age group from 1990 to 2021. Legend: temporal trends in incidence rate and mortality rate of colorectal cancer (CRC) from 1990 to 2021, stratified by age group (15–49 years, 50–69 years, and 70 + years). The figure highlights age-related differences in CRC burden over time

Age-period-cohort analysis of CRC burden

The age effect for CRC incidence exhibits a steep rise from childhood to approximately age 40, followed by a more gradual increase and a plateau at older ages.The period effect for CRC incidence demonstrates a gradual upward trend from the early 1990s until around 2007, after which the trend appears to stabilize, showing minimal change through to 2021.The cohort effect for CRC incidence declines among cohorts born from the early 1900s up to approximately the late 1930s. Following this, there is a gradual upward trend, peaking around cohorts born in the 1980s. After this peak, the trend reverses again, showing a decline in the most recent birth cohorts.

The age effect for CRC mortality increases with age, with a particularly marked rise after the age of 50.The period effect for CRC mortality exhibits a continuous downward trend.Similarly, the mortality cohort effect demonstrated a gradual decrease in risk from the early birth cohort to the later birth cohort (Fig. 6).

Fig. 6

The effects of age, period, and cohort on the risk of colorectal cancer burden globally. Legend: bayesian age-period-cohort (BAPC) analysis illustrating the relative risk of colorectal cancer (CRC) burden associated with age, period, and birth cohort effects. (A) Age effect on CRC incidence risk. (B) Age effect on CRC mortality risk. (C) Period effect on CRC incidence risk. (D) Period effect on CRC mortality risk. (E) Birth cohort effect on CRC incidence risk. (F) Birth cohort effect on CRC mortality risk. All estimates are presented on a relative risk scale, with 1.0 as the reference value

Age and sex patterns

In 2021, the global prevalence of CRC was highest among individuals aged 85–89 years. Among males, the 65–69 age group had the highest number of prevalent cases, while for females, the peak was in the 70–74 age group. The number of prevalent cases of CRC showed significant sex differences. Under 84 years of age, males had higher CRC prevalence, whereas the number of prevalent cases was higher in females among individuals aged ≥ 85 years (Fig. 7).

Fig. 7

Global number and prevalence of colon and rectum cancer by age and sex in 2021. Legend: number of prevalent cases globally and prevalence of colon and rectum cancer per 100 000 population, by age and sex in 2021. Lines indicate prevalent cases with 95% uncertainty intervals for males and females

CRC mortality rates in 2021 increased progressively with age, peaking among males aged 90–94 years. The age group with the highest number of deaths for males was 70–74 years, while it was 80–84 years among females. The distribution of deaths between sexes mirrored the pattern observed for prevalent cases (Fig. 8).

Fig. 8

Global number and death rate of colon and rectum cancer by age and sex in 2021. Legend: number of deaths globally and death rate of colon and rectum cancer per 100 000 population, by age and sex in 2021. Lines indicate death rate with 95% uncertainty intervals for males and females

For males, the global DALY rate for CRC rose steadily up to the 90–94 age group and then declined with advancing age. In contrast, the DALY rate for females continued to increase until the oldest age group (≥ 95 years). Across all age groups, males consistently had higher DALY rates compared to females. The total number of DALYs peaked in the 65–69 age group, with higher numbers observed in males within the 80–84 age range (Fig. 9).

Fig. 9

Global Number and DALYs Rate of CRC by Age and Sex in 2021. Legend: Number of DALYs globally and DALYs rate of CRC per 100 000 population, by age and sex in 2021. Lines indicate DALYs rate with 95% uncertainty intervals for males and females. DALYs, disability-adjusted life years

Risk factors

Globally, diets high in red meat were the leading contributors to CRC-related DALYs in 2021, followed by high BMI, low calcium intake, and alcohol use.

The CRC DALYs attributed to high red meat consumption in 2021 varied across income regions. Globally, 14.6% of CRC DALYs were linked to red meat consumption, with the highest proportion (15.8%) in high-income regions and the lowest (10.3%) in lower-middle-income regions (Fig. 10).

Fig. 10

CRC DALYs Attributable to Risk Factors Globally and by Region. Legend: The colon and rectum cancer DALYs attributable to risk factors, globally and by region. DALYs, disability-adjusted life years

In 2021, high BMI accounted for 9.7% of CRC DALYs globally, reflecting an increase from previous years. In high-income regions, 7.9% of CRC DALYs were attributable to high BMI (Figs. 10 and 11).

Fig. 11

Percentage Contrast of CRC DALYs Attributable to Risk Factors in 1990 and 2021. Legend: Contrast in percentage of DALYs attributable to risk factors for colorectal cancer in 1990 and 2021. DALYs, disability-adjusted life years

Diets low in calcium were responsible for 5.8% of global CRC DALYs in 2021, marking a 16.9% decrease since 1990. Despite this reduction, low calcium intake remained the leading risk factor for DALYs in regions with lower economic development, contributing 23% in lower-middle-income regions and 17.1% in low-income regions (Figs. 10 and 11).

In 2021, diets high in red meat were the primary contributors to CRC-related deaths globally, particularly in high-income and upper-middle-income regions. Conversely, diets low in calcium were the most significant contributors to CRC deaths in low-income and lower-middle-income regions (Figure S1).

In low- and lower-middle-income regions, the burden of CRC associated with low calcium intake has shown a declining trend. Similarly, in high-income regions, the effect of red meat consumption on CRC burden remained relatively unchanged, while CRC burden attributable to high BMI displayed a significant upward trend over the same period (Figs. 10 and 11).

Spatial patterns of CRC attributable to three risk factors

At the national level, the ASDR for CRC attributable to a diet high in red meat showed significant global variation in 2021. The highest rates were observed in countries within Central Europe and Southeast Latin America, with the Eastern Republic of Uruguay recording the highest ASDR (100.43 per 100,000; 95% UI: 200.29–0), followed by the Republic of Bulgaria. In contrast, 23 countries reported an ASDR below 10 per 100,000, with the lowest observed in the Democratic Socialist Republic of Sri Lanka (5.18 per 100,000; 95% UI: 11.94–0) (Fig. 12).

Fig. 12

ASDR of CRC Attributable to High Red Meat Consumption, High BMI, and Low Calcium Diet in 204 Countries and Territories. Legend: The ASDR of CRC attributable to high red meat consumption (A), high body mass index (B), and low calcium diet (C) in 204 countries and territories. ASDR, age-standardized DALYs (disability-adjusted life years) rate

For CRC attributable to high BMI, Hungary had the highest ASDR globally (92.03 per 100,000; 95% UI: 41.88–149.98). Conversely, 26 countries reported ASDRs below 10 per 100,000, with the lowest observed in the People’s Republic of Bangladesh (3.41 per 100,000; 95% UI: 1.21–6.04) (Fig. 12).

Regarding CRC attributable to a diet low in calcium, the ASDR varied dramatically, with a more than 35-fold difference between countries. Zambia had the highest ASDR (123.81 per 100,000; 95% UI: 74.17–249.01), while the Republic of Albania reported the lowest (3.54 per 100,000; 95% UI: 2.09–5.66) (Fig. 12).

Temporal trends of CRC burden attributable to three risk factors

Globally, the age-standardized years of life lost (YLL) rate for CRC attributable to a diet high in red meat decreased across high-income, upper-middle-income, and lower-middle-income regions (Fig. 13).

Fig. 13

Temporal Trends of ASDR, ASMR, YLD, and YLL Rates of CRC Attributable to Key Risk Factors Across SDI Regions from 1990 to 2021. Legend: Temporal trends of ASDR, ASMR, age-standardized YLD rate, and age-standardized YLL rate of CRC attributable to high red meat consumption, high body mass index, and low calcium diet from 1990 to 2021 in different SDI regions

The CRC burden attributable to a diet low in calcium significantly declined worldwide and across all World Bank income regions. The most substantial decrease was observed in the upper-middle-income region, where the age-standardized YLL rate dropped from 45.29 per 100,000 in 1990 to 22.81 per 100,000 in 2021 (Fig. 13).

The ASDR of CRC attributable to high BMI has increased over the past three decades in all regions, except for high-income countries. The upper-middle-income region experienced the highest increase in ASDR during this period (Fig. 13).

Compared to 1990, CRC mortality rates attributable to a diet high in red meat decreased across all age groups, with the most pronounced decline observed in the 75–79 age group. Conversely, CRC mortality rates linked to high BMI increased in all age groups except for the 65–69 and 75–79 age groups, with the largest increases recorded in younger age groups, specifically 20–24, 25–29, and 30–34 years (Table 1).

CRC mortality rates attributable to a diet low in calcium decreased markedly across all age groups since 1990. The most significant reduction occurred in the 35–39 age group, while the smallest decline was observed in individuals aged ≥ 80 years (Table 1).

For females, the ASMR of CRC attributable to diets high in red meat, high BMI, and low calcium intake has declined since 1990. Among males, the ASMR for CRC linked to diets high in red meat and low in calcium has decreased, whereas the ASMR associated with high BMI increased by 14% (95% UI: 5.03 to 24.64) (Table 2).

Table 1 Colorectal cancer mortality and associated risk factors over time (1990–2021)

Table 2 Colorectal cancer ASMR and key risk factors by gender over time (1990–2021)

Discussion

Our study found that the ASIR of CRC has continued to rise globally. Among the four income groups defined by the World Bank, the Upper Middle Income regions have exhibited a particularly marked upward trend, which warrants further investigation. This increase may be attributable to rapid economic development in many of these countries, which has led to shifts in lifestyle and dietary patterns [2]. These changes often involve increased consumption of red and processed meats, low dietary fiber intake, alcohol use, tobacco smoking, physical inactivity, and sedentary behavior. Notably, ethanol in all types of alcoholic beverages is an established risk factor for CRC [11].

Among the four World Bank income regions, the High Income group bears the greatest disease burden of CRC. However, over the past three decades, this region has experienced the most pronounced declines in both ASMR and ASDR. These improvements may be largely driven by the widespread implementation of CRC screening programs in these countries [12,13,14,15], most of which use the fecal immunochemical test (FIT) as the initial screening method due to its safety, simplicity, and high acceptability. In addition to offering free screening for high-risk populations, advancements in treatment during this period have also contributed to mortality reduction [3]. The decline in ASDR reflects not only improved therapeutic outcomes but also the earlier detection and treatment of CRC or precancerous lesions through screening, which significantly enhances patient prognosis and reduces years of healthy life lost due to disability. Moreover, postoperative care improvements may have further contributed to better outcomes in CRC patients [16].

Despite the marked downward trend, the disease burden of CRC in World Bank High Income regions remains the highest among all income groups. This may be partly explained by persistent unhealthy lifestyle behaviors and dietary patterns. Evidence suggests that obesity rates have risen over the past three decades in economically developed areas. In many high-income countries, more than half of adults aged 25 and older are now classified as overweight or obese [17].

Age-specific trends reveal a modest increase in incidence among individuals under the age of 50, while the rise is more pronounced in older adults aged 50–69 and those over 70. Although the majority of early-onset colorectal cancers (EOCRC) occur sporadically, it is essential to consider and rule out inherited syndromes in these patients [18].

Recent studies indicate that approximately 20% of EOCRC cases involve pathogenic germline variants (PGVs), highlighting the potential for these mutations to be passed on to future generations [19]. Based on this, Dr. Sinicrope has recommended that individuals diagnosed with CRC before age 50 undergo genetic risk counseling and evaluation, including germline multigene panel testing.

Moreover, a personalized screening strategy tailored to family history may allow up to 25% of individuals aged 40–49 to be identified and treated at the precancerous stage. In both approaches, the role of physician recommendation is particularly crucial in promoting timely screening and early diagnosis.

The period effect analysis revealed a distinct divergence between sexes: the risk of CRC incidence increased progressively over time in males, while it gradually declined in females. Several factors may account for this difference.

First, both smoking and alcohol consumption are established risk factors for CRC, and the prevalence of these behaviors is significantly higher among males than females [20, 21]. This highlights the ongoing importance of tobacco and alcohol control efforts in reducing the CRC burden.

Second, light to moderate alcohol intake has been associated with increased CRC risk in males but not in females [22]. Third, males appear to face a greater CRC risk associated with overweight and obesity compared to females [23].One possible explanation is that, in postmenopausal females, adipose tissue becomes the primary source of estrogen, which may offer some protective effect against CRC development [24, 25]. In contrast, increased adiposity in males tends to lower testosterone levels [26], and a cohort study has found that higher testosterone concentrations are linked to a reduced risk of CRC in males [27].

Moreover, even at equivalent BMI levels, males typically have a higher proportion of visceral adipose tissue (VAT) [28], which is a known contributor to increased CRC risk [29].

The ASIR of CRC attributable to high BMI has shown a declining trend in World Bank High Income regions. In contrast, rising trends were observed in World Bank Upper Middle, Lower Middle, and Low Income regions, with the most pronounced increase seen in the Upper Middle Income group. This pattern is likely associated with lifestyle changes driven by rapid socioeconomic development in these countries [30].

These findings underscore the importance of promoting healthy diets, regular physical activity, and effective weight management in these regions, which could play a critical role in mitigating the growing burden of CRC.

This study has several limitations. First, as a global-level analysis, it provides an overview of overall trends but lacks the detail needed to capture country-specific patterns. Future research focusing on individual countries is needed for more precise insights. Second, although the GBD methodology is robust, it may be influenced by biases in data sources, modeling, and assumptions—especially in regions without population-based cancer registries. Last but not least, GBD data reflects past disease burden, so recent changes may not be fully captured.

Conclusion

From 1990 to 2021, the global burden of CRC showed a decreasing trend, with the most substantial reductions observed in high-income regions. However, the incidence rate has continued to rise. Notably, while early-onset CRC is increasing, the rise is even more pronounced among individuals aged 50 years and older, who also exhibit a substantially higher incidence rate than those under 50.

High red meat consumption, high BMI, and low calcium intake remain the top three global risk factors for CRC. Smoking cessation and alcohol control are particularly important for reducing the CRC burden among males. Supporting individuals across all age groups in maintaining a healthy weight and promoting healthier lifestyles are critical strategies for reducing CRC risk in both males and females.