A prospective investigation of early-onset colorectal cancer risk factors–pooled analysis of three large-scale European cohorts
Ruhina Shirin Laskar, Neil Murphy, Pietro Ferrari, Paul Brennan, Amanda J. Cross, Marcela Guevara, Valeria Pala, Karl Smith-Byrne, Anne Tjønneland, Renée T. Fortner, Tonje Braaten, Therese Haugdahl Nøst, Guri Skeie, Peter T. Campbell, Marc J. Gunter, Kristin Benjaminsen Borch
Abstract
BACKGROUND: Colorectal 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). METHODS: We 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). RESULTS: 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. DISCUSSION: Adiposity, 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.