Risk Factors for Early-Onset Colorectal Cancer: A Nested Case‒Control Study within the Korean National Health Insurance Service-Health Screening Cohort

Abstract Background: Early-onset colorectal cancer (EoCRC) incidence is rising globally, but risk factors remain unclear, especially in Asian populations. This study aimed to identify modifiable risk factors for EoCRC in Korea. Methods: A nested case-control study used the National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS, 2002–2019). EoCRC cases were individuals aged 40–49 diagnosed with colorectal cancer between 2004 and 2019. Controls were matched 1:15 by birth year, sex, and screening year. Conditional logistic regression estimated adjusted odds ratios (aORs) and 95% confidence intervals (CIs). Population attributable fractions (PAFs) were calculated based on 2011 exposure prevalence using a Monte Carlo simulation. Results: Among 285 EoCRC cases (192 males, 93 females), high BMI (aOR: 1.32; 95% CI: 1.02–1.70) and a history of other cancers (aOR: 5.68; 95% CI: 3.82–8.45) were significant risk factors. The overall PAF was higher in EoCRC than in LoCRC (PAF: 18.01% vs. 16.58%), especially among females (34.16% vs. 11.19%). In males, key contributors to EoCRC included high BMI (10.52%) and prolonged smoking (7.40%). In females, high BMI (9.47%), history of other cancers (9.47%), physical inactivity (8.37%), and alcohol use (6.85%) were predominant. Conclusions: Metabolic and lifestyle-related factors, including high BMI, smoking, physical inactivity, and alcohol use, are major risk factors for EoCRC, with sex-specific differences most pronounced among females. Impact: Targeted lifestyle interventions addressing obesity, smoking, physical inactivity, and alcohol use may help prevent EoCRC, especially in high-risk groups.