Global burden of colorectal cancer mortality by age and sex, 1990–2050: a population-based analysis

Background: Colorectal cancer (CRC) represents a major global public health challenge, yet age- and sex-specific patterns in mortality burden and risk factor contributions remain incompletely characterised. We aimed to analyse global age- and sex-specific mortality patterns of CRC from 1990 to 2021, project trends to 2050, and assess the mortality burden attributable to risk factors. Methods: We extracted CRC mortality data from 204 countries and territories between 1990 and 2021 from Global Burden of Disease 2021. We stratified the population into very early-onset CRC (VEOCRC) (aged 15-34 years), early-onset CRC (EOCRC) (aged 35-49 years), and late-onset CRC (LOCRC) (aged 50-95 years). Age-specific mortality rates (MRs) characterised mortality burden, and estimated annual percentage changes quantified temporal trends. We applied population attributable fractions (PAFs) to estimate the mortality burden attributable to risk factors and used Bayesian age-period-cohort models to project global mortality trends from 2022 to 2050. Results: From 1990 to 2021, LOCRC accounted for the greatest global mortality burden, followed by EOCRC and VEOCRC. The VEOCRC and EOCRC MRs were highest in East Asia, while LOCRC rates were highest among females in Australasia and males in Western Europe. All three subtypes had the highest MRs in the high-middle sociodemographic index region. Males consistently had higher MRs than females across all three subtypes. Generally, MRs declined from 1990 to 2021 across all three CRC subtypes, although some low- and middle-income regions, particularly East Asia, Latin America, and Africa, showed increasing trends. The PAFs of risk factors increased with age, particularly for behavioural, metabolic, and dietary factors. Projections suggested declining global CRC age-standardised MRs by 2050, while LOCRC would remain the major contributor, with rates of 57.47 per 100,000 in males and 31.40 in females. Conclusions: We found substantial age, sex, and regional disparities in global CRC mortality. Despite projected declines by 2050, LOCRC will remain the dominant contributor, while younger-onset CRC warrants greater attention.