Active Cigarette Smoking, Variants in Carcinogen Metabolism Genes and Breast Cancer Risk among Pre- and Postmenopausal Women in Ontario, Canada

Cigarette smoking is strongly associated with various diseases including many cancers; however, evidence regarding breast cancer risk remains inconclusive with some studies reporting no association, and others an increased risk with long duration and early initiation of smoking. Genetic variation in carcinogen-metabolizing enzymes may modify these associations. Breast cancer cases were identified from the Ontario Cancer Registry (OCR) during 2003-2004 and population controls through random digit dialing methods. All subjects completed self-administered questionnaires. Subsequently, saliva samples were obtained from cases (N=1,776) and controls (N=1,839) for deoxyribonucleic acid (DNA) extraction. Multivariate logistic regression was used to estimate odds ratio (OR) and 95% confidence intervals (CI) for active smoking variables, and interactions were assessed between smoking and 36 carcinogen-metabolizing candidate gene variants. No statistically significant association was found between active smoking and breast cancer risk among all women nor when stratified by menopausal status; however, nonsignificant increased premenopausal breast cancer risk was observed among current smokers and women smoking before first pregnancy. Several statistically significant interactions were observed between smoking and genetic variants (CYP1A2 1548C>T, CYP1A1 3801T>C, CYP1B1 4326G>C, NAT1 c.-85-1014T>A, UGT1A7 W208R 622T>C, SOD2 c.47T>C, GSTT1 deletion). However, in analyses stratified by these genotypes, smoking ORs had wide confidence intervals (and with few exceptions included 1.0) making interpretations difficult. Active smoking was not associated with breast cancer risk, although several significant interactions were observed between smoking, carcinogen-metabolizing genetic variants, and breast cancer risk.