Obesity-Driven Early-Onset Colorectal Cancer: Mechanistic Insights and Emerging Clinical Implications

Abstract

Early-onset colorectal cancer (EOCRC), defined as colorectal cancer diagnosed before 50 years of age, has increased markedly over the past decades, especially in high-income settings. In parallel, obesity and related metabolic disturbances have become more common in both adults and younger populations, raising the possibility that excess adiposity contributes to the changing EOCRC burden. Epidemiological studies increasingly support this association, particularly for early-life adiposity and persistent metabolic dysfunction. Most EOCRC cases are sporadic, indicating that environmental and lifestyle-related exposures likely play a major role. Among these, obesity may be especially important because it links systemic metabolic stress with intestinal inflammation, microbial imbalance, and epigenetic change. However, the mechanisms through which obesity promotes early colorectal carcinogenesis are still not fully defined. In this review, we examine how obesity may shape EOCRC development across four interacting domains: chronic inflammation, metabolic reprogramming, gut microbiota dysbiosis, and epigenetic remodeling. We also discuss how these pathways may converge during early-life windows of susceptibility and consider their implications for risk identification, prevention, and early intervention in younger populations.