EFFECT OF SMOKING ON BREAST-CANCER IN CARRIERS OF MUTANT BRCA1 OR BRCA2 GENES

Background: Smoking has carcinogenic effects, and possibly antiestroge nic effects as well, but it has not been found to be a risk factor for breast cancer in women in the general population. However, hereditary breast cancer is primarily a disease of premenopausal women, and inte ractions between genes and hormonal and environmental risk factors may be particularly important in this subgroup. Methods: We conducted a m atched case-control study of breast cancer among women who have been i dentified to be carriers of a deleterious mutation in either the BRCA1 or the BRCA2 gene. These women were assessed for genetic risk at one of several genetic counseling programs for cancer in North America, In formation about lifetime smoking history was derived from a questionna ire routinely administered to women who were found to carry a mutation in either gene. Smoking histories of case subjects with breast cancer and age-matched healthy control subjects were compared. Odds ratios f or developing breast cancer were determined for smokers versus non-smo kers by use of conditional logistic regression for matched sets after adjustment for other known risk factors. Results: Subjects with BRCA1 or BRCA2 gene mutations and breast cancer were significantly more like ly to have been nonsmokers than were subjects with mutations and witho ut breast cancer (two-sided P = .007). In a multivariate analysis, sub jects with BRCA1 or BRCA2 mutations who had smoked cigarettes for more than 4 pack-years (i.e., number of packs per day multiplied by the nu mber of years of smoking) were found to have a lower breast cancer ris k (odds ratio = 0.46, 95% confidence interval = 0.27-0.80; two-sided P = .006) than subjects with mutations who never smoked. Conclusions: T his study raises the possibility that smoking reduces the risk of brea st cancer in carriers of BRCA1 or BRCA2 gene mutations.