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Weight History, Smoking, Physical Activity and Breast Cancer Risk among French-Canadian Women Non-Carriers of More Frequent BRCA1/2 Mutations 

Our study showed that more than 9 pack-years of smoking had a significant positive association with breast cancer risk among both pre- and postmenopausal women; however, this result does not support our previous report of a reduced risk of breast cancer in carriers of BRCA gene mutations who had smoked more than 4 pack-years [28]. The weaker breast cancer risk in these subjects may have been associated with lower levels of circulating estrogens [29]. In contrast, a recent case-control study among Polish women indicated an increased risk of invasive breast cancer with the consumption of ≥10 cigarettes/d among both premenopausal (OR = 2.55; 95% CI: ) and postmenopausal (OR = 1.78; 95% CI: ) women [30]. Likewise, another recent study [31] suggested that BRCA mutation carriers who smoked had 2.3-fold (95% CI: ) and 2.6-fold (95% CI: ), respectively, greater risk of breast cancer. Cigarette smoke contains compounds that damage DNA, and the repair of such damage may be impaired in women with germline mutations. Some genotoxic carcinogens in tobacco smoke are mammary carcinogens in rodents [32]. The enzymatic machinery required for their metabolic activation is present in human mammary epithelial cells [33], and there is evidence of carcinogen-DNA adducts in human mammary tissue [34, 35], some of which may be smoking-related.

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