Abstract IA002: Early-Onset Colorectal Cancer as a Model for Precision Cancer Prevention

Abstract The rising incidence of early-onset colorectal cancer (EOCRC) —diagnosed before age 50—represents a sentinel trend for other early-onset cancers. While EOCRC is the most well-characterized early-onset malignancy, it also serves as a model for understanding shared mechanisms and prevention strategies across tumor types. Current prevention efforts emphasize earlier screening, yet early detection and interception alone cannot address the growing burden of early-onset cancers, particularly as carcinogenic processes may begin decades before diagnosis. Because early-onset cancers remain relatively rare, advancing risk stratification is critical to identify individuals most likely to benefit from early intervention. Accumulating evidence implicates early-life and mid-life exposures—including diet, obesity, sedentary behavior, and gut microbial dysbiosis—in shaping cancer susceptibility. These insights call for a life course prevention framework that integrates molecular and microbial biomarkers into precision risk models. Promising strategies include aspirin to block inflammation, GLP-1 receptor agonists to reverse obesity-related metabolic dysfunction, and dietary interventions—such as high-fiber and plant-forward diets—to favorably modulate the microbiome and reduce systemic inflammation. By viewing EOCRC as both a sentinel and prototype, we can move beyond early detection toward proactive, risk-targeted prevention—disrupting carcinogenic pathways before disease emerges and reimagining cancer control across the lifespan. Citation Format: Andrew T. Chan. Early-Onset Colorectal Cancer as a Model for Precision Cancer Prevention abstract. In: Proceedings of the AACR Special Conference in Cancer Research: The Rise in Early-Onset Cancers—Knowledge Gaps and Research Opportunities; 2025 Dec 10-13; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2025;31 (23Suppl): Abstract nr IA002.