Abstract
BackgroundColorectal cancer (CRC) incidence is rising among adults under 55 years, but its causes remain unclear. Large-scale prospective studies are needed to identify risk factors for early-onset CRC (EOCRC).MethodsWe pooled three large European prospective cohort studies, examining 14 known or suspected risk factors with EOCRC (diagnosed <55 years, N = 1369) and later-onset CRCs (LOCRC) (diagnosed ≥55 years, N = 13,490). Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs).ResultsHigher body mass index (BMI, per 5 kg/m2 increase), was strongly associated with EOCRC in men (HR 1.33, 95% CI: 1.18-1.51), particularly for early-onset colon cancer (HR 1.55, 95% CI: 1.32-1.82), compared to later-onset disease (HR 1.25, 95% CI: 1.19-1.31) (Phet = 0.01). Weaker associations with BMI were observed for women and rectal cancers. Similar sex and subsite specific trends were observed for waist circumference and waist-to-hip ratio. Current smoking (HR 1.24, 95% CI: 1.07-1.44) and alcohol use (HR 1.15, 95% CI: 1.06-1.25) increased EOCRC risk, and physical activity (HR 0.71, 95% CI: 0.54-0.95) was protective.DiscussionAdiposity, physical inactivity, smoking, and alcohol consumption are risk factors for EOCRC. Risk factors were largely similar between EOCRC and LOCRC, except for adiposity, with stronger EOCRC association in men.</p>