A prospective investigation of early-onset colorectal cancer risk factors–pooled analysis of three large-scale European cohorts

Journal article

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: Higher 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. 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.

Authors: Laskar, RS; Murphy, N; Ferrari, P; Brennan, P; Cross, AJ

• Alternative title: Epidemiology
• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Springer Nature [academic journals on nature.com]
• Journal: British Journal of Cancer
• Volume: 134
• Issue: 5
• Pages: 781-789
• Publication date: 2025-12-20
• Acceptance date: 2025-12-03
• DOI: 10.1038/s41416-025-03303-y
• EISSN: 1532-1827
• ISSN: 0007-0920
• Language: English