State-level burden of early onset colorectal cancer in the US: a Global Burden of Disease study, 1980 to 2021

BACKGROUND: Early-onset colorectal cancer (EOCC) is an escalating clinical challenge. While national incidence is rising, aggregated data may obscure critical differences in mortality trends and geographic burden that are essential for clinical risk assessment. METHODS: We utilized the Global Burden of Disease (GBD) 2021 study to analyze incidence, mortality, and disability-adjusted life years (DALYs) for colorectal cancer in US adults aged <50 years. Data were stratified by fine 5-year age groups and US state from 1990 to 2021. RESULTS: Nationally, incidence rates increased consistently across all cohorts aged 25 to 49 years from 1990 through 2021. In contrast, mortality and DALY rates exhibited a U-shaped trajectory for the 30 to 49 age strata: declining until the mid-2000s, followed by a persistent resurgence through 2021. This mortality reversal was most pronounced in the Southern Census regions. In 2021, the burden was disproportionately concentrated in East South Central and West South Central states, with Mississippi, Kentucky, and West Virginia exhibiting mortality rates up to twofold higher than states in New England or the Pacific West. CONCLUSION: The decoupling of incidence and mortality trends suggests that therapeutic advances are no longer sufficient to offset the accelerating incidence of EOCC in the 30 to 49 age demographic. The distinct geographic clustering of advanced disease burden warrants heightened diagnostic vigilance for symptomatic young adults, particularly in high-prevalence Southern and Appalachian regions.