Colorectal cancer (CRC) is a leading cause of cancer mortality worldwide. Together with other gastrointestinal malignancies (gastric cancer, esophageal cancer, pancreatic cancer, hepatocellular carcinoma), it accounts for approximately one-third of all cancer-related DALYs (1–4). As a common digestive tract malignancy, CRC ranks third in global incidence and second in mortality among all malignant tumors (5, 6). In 2018, the International Agency for Research on Cancer reported that the highest incidence rates of colon cancer were observed in Europe, North America, Australia, New Zealand, and East Asia, and in 2020, CRC emerged as the world’s third most prevalent cancer, with 2 million new cases recorded that year, it was also among the top causes of cancer-related deaths (7, 8).

The etiology and pathogenesis of CRC remain incompletely understood, but can be broadly categorized into genetic factors, environmental factors, and lifestyle conditions (9, 10). CRC incidence has risen annually, paralleling the growing prevalence of high-fat, low-fiber diets. While tobacco and alcohol are established risk factors for several cancers, the mechanism linking smoking to CRC remains unclear (11–13).

Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021, this analysis presents estimates of CRC incidence, mortality, ASIR, ASDR, and DALY rates across 204 countries and territories from 1990 to 2021, stratified by age and sex. It also reports age-standardized DALYs by SDI and estimates the proportion of DALYs attributable to key CRC risk factors (tobacco smoking, alcohol consumption, low physical activity, high body mass index [BMI]). The goal is to provide actionable insights for policymakers, funders, and researchers to develop region-specific interventions, optimize healthcare resource allocation, and guide future CRC research.

This study provides a comprehensive analysis of the global Colorectal cancer (CRC) burden from 1990 to 2021, highlighting significant disparities across SDI (Socio-demographic Index) regions. The global CRC incidence more than doubled over 32 years, consistent with previous research on rising global CRC trends (17, 18).

Between 1990 and 2021, incidence and mortality rates declined in high SDI countries but rose in some low-middle and middle SDI regions. Low, low-middle, middle, high-middle, and high SDI regions saw a 291.4% increase in incident cases (from 76.7% of the global total) and a 169.3% increase in deaths (from 38.4% of global deaths). The proportion of global DALYs (disability-adjusted life years) from these regions grew from 25.5% to 151.1%.

We observed substantial increases in ASIR (age-standardized incidence rates) between 1990 and 2021 across Asia—for instance, 65.4% in East Asia and 56.6% in Southeast Asia—and Latin America, including 90.3% in Central Latin America and 56.4% in Tropical Latin America.

Driven by rapid economic growth and industrialization, the expanding middle class in developing nations has adopted Westernized lifestyles marked by unhealthy dietary patterns (low fruit and vegetable intake, high consumption of red and processed meats), sedentary behaviors (e.g., prolonged television viewing), reduced physical activity, and substance use (alcohol and tobacco) (19). Such behavioral shifts contribute to the rising incidence of lifestyle-related diseases, including CRC.

Furthermore, advancements in medical screening technologies have also contributed to higher detection rates of CRC in high-middle SDI regions (20–24). Conversely, owing to constrained healthcare resources and limited medical expertise, many CRC cases in low SDI regions remain undiagnosed or unrecorded (17, 25). While the current burden of CRC in lower SDI regions is relatively low, attention must be paid to rising trends in alcohol consumption and metabolic risk factors. Recent research highlights significant increases in metabolic disorders and alcohol-related complications in these regions (26–28), which may drive a future surge in CRC cases. Thus, overly optimistic conclusions about the current burden are unwarranted. Proactive public health interventions and sustained monitoring are critical to mitigating these emerging risks in vulnerable populations (18).

The CRC screening guidelines adopted by different countries may influence the disease burden of CRC. Most nations recommend initiating CRC screening for the general risk population at age 50 (21, 29–31). With growing attention to CRC, China’s CRC Screening Guidelines lowered the screening initiation age for the general risk population to 40 in 2020 (32). Similarly, the US Preventive Services Task Force (USPSTF) revised its recommendation in 2021, reducing the initial CRC screening age from 50 to 45 (33, 34). Japan, by contrast, has mandated routine CRC screening for adults aged 40 and above since as early as 1992 (29). Our findings reveal that the mortality rates of CRC in Japan, China, and the United States rank significantly lower than their respective incidence rates. Studies indicate that between 1990 and 2019, Japan exhibited the lowest CRC mortality-to-incidence ratio across Asia (35). This suggests that while early screening may not reduce the incidence of CRC, it could mitigate the risk of fatal outcomes associated with the disease. However, these findings require further research to be confirmed.

Our study revealed that while the incidence, mortality, and DALYs related to CRC have risen sharply over the past three decades, their proportions relative to the overall burden of CRC have been on the decline. This outcome indicates that the growth rate of the disease burden associated with CRC is relatively slower compared to that of all CRC cases. Such findings are consistent with those reported in other studies (20, 36). A potential explanation lies in the fact that age is a well-established risk factor for CRC, and this is compounded by the effects of increased life expectancy and a growing aging population (37). As a result, CRC in elderly populations has emerged as a critical public health issue demanding targeted attention.

Data from the study shows that early-onset CRC (EO-CRC, 25–49 age group) incidence rose significantly, with 25–74 age group up notably by 2021 vs 1990 and SDI-based regional differences. High-SDI regions saw EO-CRC rise in 25-49s despite lower 55-89s incidence; middle-low SDI regions had more obvious EO-CRC growth, and young men were at higher risk. Young people’s behavioral risks may drive this. With insufficient research on EO-CRC mechanisms in youth, targeted interventions and lower screening age are needed to reduce its burden.

The precise cause behind the rising incidence of CRC in individuals under 50 remains elusive, but one plausible explanation may lie in the birth cohort effect: those born in the latter half of the 20th century have faced growing exposure to modifiable behavioral risk factors, including unhealthy dietary patterns, obesity, sedentary lifestyles, reduced physical activity, and elevated smoking rates during early adulthood (14). However, most of these risk factors have been identified based on evidence derived from CRC patients aged 50 or older, leaving the exact mechanisms and underlying risk factors for younger populations relatively unclear (38–41).

Notable disparities exist in the disease burden of CRC across continents and countries, even among regions with similar SDI levels. These differences may arise from variations in population size, lifestyle trends, ethnic genetics, and healthcare access. Prior research highlights the significant role of ethnicity in CRC development within East Asia: certain ethnic groups, such as the Chinese, Koreans, and Japanese, exhibit higher incidence rates. Even in ethnically diverse countries like Singapore and Malaysia—where different racial groups share similar environmental conditions and dietary habits—Chinese populations show a significantly elevated risk of CRC compared to Malays and Indians. Additionally, within the same ethnic group in China, individuals residing in coastal areas experience higher incidence and mortality rates than their inland counterparts (42, 43).

A major limitation of this study is the lack of cancer registry data in many African, Caribbean, and Asian countries. While GBD uses available data from vital registries, oral autopsy, etc., the accuracy of its estimates is heavily dependent on cancer registry data, which is lacking or inadequately covered in many low - and middle-income countries in sub-Saharan Africa and Asia, with underreporting due to poor documentation, inadequate facilities/staff, etc. In addition, 95% ui (uncertainty interval) cannot account for bias such as measurement or selection bias. Second, because of the longer statistical period, inadequate disease registration up to 30 years ago (especially in low - and middle-income countries) may have biased earlier (1990s) estimates, as reflected in the wide 95% ui. Third, delays in reporting cancer data in 2021, even in regions with high SDI, led to recent trend-based estimates using a broader ui.

In conclusion, global CRC incidence and mortality have more than doubled in three decades. Mitigating modifiable risks and boosting screening are key to reducing deaths. Low and middle SDI regions (accounting for ~75% of DALYs) will see further rises due to aging, longer lifespans, better detection, and lifestyle shifts. Strategies like lifestyle adjustments, early screening, quality healthcare, and advanced treatments are critical. Population-based registries aid monitoring. The rising incidence in those <50 is a warning, requiring greater awareness and research into its drivers.

Data generated by the Global Burden of Disease study serves as a vital resource for both the general public and healthcare providers, as it illuminates the effectiveness of current treatment strategies, the impacts of past interventions, and the necessity of implementing preventive measures. The findings from GBD 2021 not only offer actionable insights for policymakers but also provide fresh perspectives for scientists and physicians worldwide. These comprehensive and comparable estimates can inform efforts to advance equitable CRC control on a global scale, with the overarching goal of alleviating the global cancer burden.