Effect of Smoking on Breast Cancer in Carriers of Mutant BRCA1 or BRCA2 Genes

Abstract

Background: Smoking has carcinogenic effects, and possibly antiestrogenic ef fects as well, but it has not been found to be a risk factor for breast cancer in women in the general population. How ever, hereditary breast cancer is pria disease of premenopausal women, and interactions between genes and hormonal and environmental risk factors may be particularly important in this subgroup. Methods: We con ducted a matched case-control study of breast cancer among women who have been identified to be carriers of a del eterious mutation in either the BRCA1 or the BRCA2 gene. These women were assessed for genetic risk at one of sev eral genetic counseling programs for cancer in North America. Information about lifetime smoking history was de rived from a questionnaire 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 com pared. Odds ratios for developing breast cancer were determined for smokers versus nonsmokers by use of conditional logistic regression for matched sets after adjustment for other known risk factors. Results: Subjects with BRCA1 or BRCA2 gene muta tions and breast cancer were signifi cantly more likely to have been nonthan were subjects with mutations and without breast cancer (two-sided P= .007). In a multivariate analysis, subjects with BRCA1 or BRCA2 mutations who had smoked cigarettes for more than 4 pack-years (i.e., number of packs per day multi plied by the number of years of smok ing) were found to have a lower breast cancer risk (odds ratio = 0.46, 95% confidence interval = 0.27-0.80; twoP = .006) than subjects with mutations who never smoked. Conclusions: This study raises the possibility that smoking reduces the risk of breast cancer in carriers of BRCA1 or BRCA2 gene mutations. [J Natl Cancer Inst 1998;90:761-6]