Widening Health Inequality and Causal Metabolic Drivers in Global Colorectal Cancer: A Multi-Dimensional Study
Song Gao, Mingying Peng, Susu Han, Yufei Tang, Juan Ren, Yi Cen, Fenggang Hou, Lianyu Chen, Xiaoling YinObjectives:
To describe the geographical distribution of global colorectal cancer (CRC) and the time trend of its disease burden from 1990 to 2021, and to predict its future development.
Methods:
Data were derived from the Global Burden of Disease Study 2021 (GBD 2021, IHME database), covering 204 countries and 21 GBD regions. Analyses were conducted both globally and stratified by socio-demographic index (SDI) region. Three-stage analysis was carried out around incidence, mortality and disability-adjusted life years (DALYs): trend analysis by Joinpoint regression and age-period-cohort model; decomposition of disease burden drivers by Das Gupta decomposition and data envelopment analysis; 15-year forecasting based on the Bayesian age-period-cohort analysis. In addition, the causal effect of BMI on CRC risk was assessed using the Mendelian randomization (MR) method.
Results:
In 2021, 2.19 million new CRC cases were reported globally (age-standardized incidence rate 25.61/100 000). From 1990 to 2021, the incidence rate continued to rise, while the mortality rate and DALYs declined — a divergence likely attributable to improved screening and treatment, particularly in high-SDI regions. Population aging is the primary driving factor for the increased CRC global burden (47.44%), while population growth is dominant in low SDI regions. Health inequality increased, and the slope index rose from 437 in 1990 to 575 in 2021. Projections showed that the incidence rate will increase slightly (+0.56%) by 2036, while the mortality rate (−9.5%) and DALYs (−8.1%) will continue to decline. MR analysis supported a causal association between BMI and increased CRC risk.
Conclusion:
The global CRC burden remains substantial, driven by population aging, the obesity epidemic, and widening regional disparities. Strategies should prioritize age-targeted screening in high-SDI regions, expand early detection in low-SDI areas, and integrate obesity control into national non-communicable disease prevention frameworks.