Trends on the incidence of early-onset colorectal cancer in the United States: an age-period-cohort analysis

Abstract

Early-onset colorectal cancer (EO-CRC) has increased over recent decades, even as incidence among older adults has declined, and the drivers of this divergence remain poorly understood. We conducted an age–period–cohort analysis of EO-CRC among adults aged 20–54 years using population-based cancer registry data from the United States for the period 2000–2022. Cases were identified by ICD-O topography codes C18–C20, and age-specific incidence rates per 100,000 person-years were stratified by sex, race and ethnicity, county-level income, and tumor location. APC effects were estimated using log-linear Poisson regression, with the Intrinsic Estimator as a complementary approach. In considering different dimensions in the APC analysis, the age effect was nonlinear, accelerating notably past age 40 years. Period effects were modest across most demographic and tumor location subgroups, with IRRs ranging from 0.98 to 1.04 (95% CIs: 0.95–1.12) during 2015–2019 and between 0.91 and 1.12 (95% CIs: 0.76–1.20) during 2020–2022. Cohort effects reflected a pattern of rising risk across successive birth cohorts: the 1994 and 1999 cohorts showed the largest increases relative to the 1965 cohort, with IRRs from 1.3 to 2.1 (95% CI: 1.18–2.70). These increases were most pronounced for rectal cancers (IRR: 1.77–1.82; 95% CI: 1.60–2.06). The disproportionate and subsite-specific nature of the cohort effect in rectal cancer may offer an important signal regarding the specific nature of exposures contributing to the growing burden of EO- CRC.