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

[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 (2002-2019). EoCRC cases were individuals ages 40 to 49 years 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 ORs (aOR) and 95% confidence intervals (CI). Population attributable fractions (PAF) were calculated based on 2011 exposure prevalence using a Monte Carlo simulation.

[RESULTS] Among 285 EoCRC cases (192 males and 93 females), high body mass index (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 late-onset colorectal cancer (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. See related In the Spotlight, p. 494.