The Increased Risk of Colon Cancer Due to Cigarette Smoking May Be Greater in Women than Men

BACKGROUND: Smoking is a recently established risk factor for colon cancer. We wanted to explore the hypothesis that women may be more susceptible to smoking-attributed colon cancer than men as one of the possible explanations for the high colon cancer risk of Norwegian women. METHODS: We followed 602,242 participants aged 19 to 67 years at enrollment in 1972-2003, by linkage to national registries through December 2007. We used Cox proportional hazard models to estimate HRs and 95% confidence intervals (CI). RESULTS: During a mean follow-up of 14 years, altogether 3,998 (46% women) subjects developed colon cancer. Female ever-smokers had a 19% (HR = 1.19, 95% CI = 1.09-1.32) and male ever-smokers an 8% (HR = 1.08, CI = 0.97-1.19) increased risk of colon cancer compared with never smokers. For all the four dose-response variables examined, female ever-smokers in the most exposed category of smoking initiation, (HR = 1.48, 95% CI = 1.21-1.81), of daily cigarette consumption (HR = 1.28, 95% CI = 1.06-1.55), of smoking duration (HR = 1.47, 95% CI = 1.11-1.95), and of pack-years of smoking (HR = 1.33, 95% CI = 1.11-1.57) had a significantly increased risk of more than 20% for colon cancer overall and of more than 40% for proximal colon cancer, compared with never smokers. A test for heterogeneity by gender was statistically significant only for ever smoking and risk of proximal colon cancer (Wald χ(2), P = 0.02). CONCLUSIONS: Female smokers may be more susceptible to colon cancer and especially to proximal colon cancer than male smokers. IMPACT: Women who smoke are more vulnerable to colon cancer than men.