Modifiable risk factors contributing to the rising incidence of early-onset colorectal cancer in the United States over three decades: a Global Burden of Disease analysis.

BACKGROUND: Early-onset colorectal cancer (EOCRC), diagnosed in adults under the age of 50 years, is a significant public health challenge in the United States (US). While traditional colorectal cancer (CRC) incidence in older populations has declined due to screening, rates among younger adults are rising, likely driven by shifting birth cohort exposures to modifiable risk factors. This study aims to quantify the longitudinal burden of EOCRC and evaluates the contribution of dietary and metabolic risks from 1990 to 2023. METHODS: Using data from the Global Burden of Disease (GBD) 2023 study, we analyzed age-specific incidence, mortality, prevalence, and disability-adjusted life years (DALYs) for EOCRC. Trends were evaluated using joinpoint regression to calculate annual percent changes (APCs). Risk factor attribution was performed for dietary, metabolic, and behavioral exposures. Future burdens were projected to 2050 using mixed-effects and autoregressive integrated moving average (ARIMA) models. RESULTS: Between 1990 and 2023, the age-specific incidence rate (ASIR) of EOCRC increased by 47.1%, rising from 8.01 to 11.79 per 100,000. Age-specific mortality rose from 2.48 to 3.00, and DALYs increased from 125.41 to 150.82. Males consistently carried a higher burden, with widening sex disparities in incidence by 2023 (13.10 in males versus 10.44 in females). By 2023, diet high in processed meat (18.4%) surpassed diet low in whole grains (17.6%) as the leading modifiable contributor to EOCRC mortality, followed by high body-mass index and smoking. Under a risk-reduction scenario, projected mortality could decline by more than 50% by 2050 (1.14 per 100,000) compared to the reference trend (2.42 per 100,000). CONCLUSIONS: The EOCRC burden in the US has intensified over three decades. The shifting dominance toward processed meat and metabolic dysfunction highlights a critical need for targeted primary prevention. Achieving significant mortality reductions by 2050 will require population-level interventions addressing dietary quality and metabolic health early in life.