Cigarette Smoking and Colorectal Cancer Risk in the European Prospective Investigation Into Cancer and Nutrition Study

BACKGROUND & AIMS: There has been consistent evidence for a relationship between smoking and colorectal cancer (CRC), although it is not clear whether the colon or rectum is more sensitive to the effects of smoking. We investigated the relationships between cigarette smoking and risk of CRC and tumor location. METHODS: We analyzed data from 465,879 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) study; 2741 developed CRC during the follow-up period (mean, 8.7 years). Cox proportional hazard regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: The risk of colon carcinoma was increased among ever smokers (HR, 1.18; 95% CI, 1.06-1.32) and former cigarette smokers (HR, 1.21; 95% CI, 1.08-1.36), compared with never smokers; the increased risk for current smokers was of borderline significance (HR, 1.13; 95% Cl, 0.98-1.31). When stratified for tumor location, the risk of proximal colon cancer was increased for former (HR, 1.25; 95% CI, 1.04-1.50) and current smokers (HR, 1.31; 95% CI, 1.06-1.64), but the risks for cancers in the distal colon or rectum were not. Subsite analyses showed a nonsignificant difference between the proximal and distal colon (P=.45) for former smokers and a significant difference for current smokers (P=.02). For smokers who had stopped smoking for at least 20 years, the risk of developing colon cancer was similar to that of never smokers. CONCLUSIONS: Ever smokers have an increased risk of colon cancer, which appeared to be more pronounced in the proximal than the distal colon location.