Early-Onset Colorectal Cancer: Epidemiology, Etiologic Pathways, and Emerging Prevention Strategies.

Abstract

Early-onset colorectal cancer (EOCRC), defined as CRC diagnosed before age 50, is rising globally despite declining incidence in older adults, representing a growing public health concern. This review synthesizes current evidence on EOCRC epidemiology, molecular features, etiologic hypotheses, and clinical implications, with an emphasis on life-course risk. Epidemiologic data demonstrate a strong birth cohort effect, implicating generational exposures in disease pathogenesis. Younger patients more often present with symptomatic, advanced-stage disease and show a predominance of distal and rectal tumors. Molecular analyses reveal modest differences from late-onset CRC, including lower BRAF mutation rates and predominance of microsatellite-stable, chromosomal instability tumors, without a defining molecular signature. Current evidence supports a multifactorial etiologic model involving metabolic dysfunction, Western dietary patterns, microbiome disruption, antibiotic exposure, and environmental factors. These exposures likely interact with genetic and epigenetic susceptibility over time to accelerate established colorectal carcinogenesis pathways rather than produce a distinct biologic entity. Among these, obesity and diet have the strongest epidemiologic support, while other contributors remain under investigation. Clinically, EOCRC highlights limitations of age-based screening and the need for improved symptom recognition, earlier diagnosis, and risk-stratified screening approaches. Prevention strategies should extend beyond midlife screening to target modifiable exposures earlier in life. EOCRC may often reflect accelerated carcinogenesis within established pathways, although conflicting molecular findings and potential biologic subsets warrant further investigation.