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This study examines global trajectories in the colorectal cancer burden, explores associated factors, and predicts future trends.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Data on the colorectal cancer burden for 204 countries and territories from 1990 to 2021 were sourced from the Global Burden of Disease Study. Growth mixture models identified subgroups of age\u2010standardized incidence and mortality rates. Eleven modifiable risk factors and four socioeconomic determinants were analyzed across the subgroups. Trends to 2040 were predicted using a Bayesian age\u2010period\u2010cohort model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Three trajectories of colorectal cancer burden were observed: slowly increasing, rapidly increasing, and slowly decreasing age\u2010standardized incidence rate, corresponding to stable, increasing, and decreasing mortality rate. Most countries showed slowly increasing incidence rates (49.0%, <jats:italic>n<\/jats:italic>\u2009=\u2009100) and stable age\u2010standardized mortality rates (51.0%, <jats:italic>n<\/jats:italic>\u2009=\u2009104). Latin America and the Caribbean predominantly have a rapidly increasing trend (age\u2010standardized incidence: 69.7%; mortality rates: 63.6%), while high\u2010income countries largely followed decreasing trajectories (incidence: 58.3%; mortality: 75.0%). Higher sociodemographic index, universal health coverage, health expenditure, and gross domestic product per capita were linked to decreasing trends (all <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). Low consumption of whole grains and milk, and excessive red meat consumption, contributed significantly to colorectal cancer mortality. However, the impact of behavioral factors such as physical inactivity, smoking, and alcohol consumption was relatively small. Mortality attributable to high fasting blood sugar and body mass index is rising. Despite a slight global decline in mortality, disparities are projected to persist through 2040.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Global disparities in colorectal cancer burden highlight the need for targeted interventions, particularly focusing on dietary factors and health inequities.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cai2.70020","type":"journal-article","created":{"date-parts":[[2025,7,9]],"date-time":"2025-07-09T15:29:43Z","timestamp":1752074983000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Global Trajectories of Colorectal Cancer Burden From 1990 to 2021 and Projection to 2040"],"prefix":"10.1002","volume":"4","author":[{"given":"Xiaolu","family":"Chen","sequence":"first","affiliation":[{"name":"Office of Cancer Screening, National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital Chinese Academy of Medical Sciences and Peking 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