Background & Aims: Cigarette smoking is a putative risk factor for colorectal cancer (CRC). However, long-term CRC risk estimates among female smokers remain limited and inconsistent. The goal of this prospective study was to assess cigarette smoking and CRC risk, overall and by anatomic subsite, among postmenopausal women. Methods: Data were drawn from a large population-based cohort (n = 41,836) of randomly selected women, age 55-69 years at baseline (Iowa Women's Health Study). Cigarette smoking and other CRC risk factors were characterized at baseline (1986). Incident (n = 869) and fatal (n = 249) CRC cases were identified through December 31, 1999. CRC risks were estimated using Cox proportional hazards regression models. Results: Compared with never smokers, ever smokers had slightly increased risks for both incident (relative risk [RR], 1.17; 95% confidence interval [Cl], 1.00-1.36) and fatal (RR, 1.3:1; 95% Cl, 0.98-1.74) CRC in multivariate analyses. Incident CRC risks increased progressively by lengthening induction period (P trend=0.01), reaching a 30% increase (RR, 1.30; 95% Cl, 1.04-1.63) after age 45 years. By anatomic subsite, ever smoked cigarettes and induction period were more strongly associated with incident proximal CRC (P = 0.03 and P trend = 0.03, respectively) than incident distal CRC (P = 0.44 and P trend = 0.10, respectively). Conclusions: In this long-term cohort study of postmenopausal women, cigarette smoking was positively associated with CRC risk. Onset of smoking in the distant past appeared to confer the greatest risk, especially for incident proximal CRC. These data support a potential subsite-specific role for cigarette smoking in colorectal carcinogenesis, at least among women. Based on emerging data, an epigenetic pathway for smoking-induced CRC is proposed.
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