title: Effect of smoking on breast cancer in carriers of mutant BRCA1 or BRCA2 genes.
abstract: BACKGROUND
  Smoking has carcinogenic effects, and possibly antiestrogenic 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 interactions between genes and hormonal and environmental risk factors may be particularly important in this subgroup.
  
  
  METHODS
  We conducted a matched case-control study of breast cancer among women who have been identified 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. Information about lifetime smoking history was derived 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 compared. 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 mutations and breast cancer were significantly more likely to have been nonsmokers than 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 multiplied by the number of years of smoking) were found to have a lower breast cancer risk (odds ratio = 0.46, 95% confidence interval = 0.27-0.80; two-sided P = .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.
authors.affiliation: Department of Medicine, Women's College Hospital, University of Toronto, ON, Canada.
authors.forename: J S
authors.initials: JS
authors.lastname: Brunet
authors.forename: P
authors.initials: P
authors.lastname: Ghadirian
authors.forename: T R
authors.initials: TR
authors.lastname: Rebbeck
authors.forename: C
authors.initials: C
authors.lastname: Lerman
authors.forename: J E
authors.initials: JE
authors.lastname: Garber
authors.forename: P N
authors.initials: PN
authors.lastname: Tonin
authors.forename: J
authors.initials: J
authors.lastname: Abrahamson
authors.forename: W D
authors.initials: WD
authors.lastname: Foulkes
authors.forename: M
authors.initials: M
authors.lastname: Daly
authors.forename: J
authors.initials: J
authors.lastname: Wagner-Costalas
authors.forename: A
authors.initials: A
authors.lastname: Godwin
authors.forename: O I
authors.initials: OI
authors.lastname: Olopade
authors.forename: R
authors.initials: R
authors.lastname: Moslehi
authors.forename: A
authors.initials: A
authors.lastname: Liede
authors.forename: P A
authors.initials: PA
authors.lastname: Futreal
authors.forename: B L
authors.initials: BL
authors.lastname: Weber
authors.forename: G M
authors.initials: GM
authors.lastname: Lenoir
authors.forename: H T
authors.initials: HT
authors.lastname: Lynch
authors.forename: S A
authors.initials: SA
authors.lastname: Narod
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000517:prevention & control*; D016022:Case-Control Studies; D004965:Estrogen Antagonists / Q000494:pharmacology; D005260:Female; D006579:Heterozygote; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D009376:Neoplasms, Hormone-Dependent / Q000235:genetics* / Q000517:prevention & control*; D016017:Odds Ratio; D012306:Risk; D012907:Smoking
chemical_list: D004965:Estrogen Antagonists