Smoking and the risk of breast cancer in BRCA1 and BRCA2 carriers: an update

Abstract

Among women with a mutation in BRCA1 or BRCA2, the risk of breast cancer is high, but it may be modified by exogenous and endogenous factors. There is concern that exposure to carcinogens in cigarette smoke may increase the risk of cancer in mutation carriers. We conducted a matched case-control study of 2,538 cases of breast cancer among women with a BRCA1 (n = 1,920) or a BRCA2 (n = 618) mutation. One non-affected mutation carrier control was selected for each case, matched on mutation, country of birth, and year of birth. Odds ratios were calculated using conditional logistic regression, adjusted for oral contraceptive use and parity. Ever-smoking was not associated with an increased breast cancer risk among BRCA1 carriers (OR = 1.09; 95% CI 0.95-1.24) or among BRCA2 carriers (OR = 0.81; 95% CI 0.63-1.05). The result did not differ when cases were restricted to women who completed the questionnaire within two years of diagnosis. A modest, but significant increase in risk was seen among BRCA1 carriers with a past history of smoking (OR = 1.27; 95% CI 1.06-1.50), but not among current smokers (OR = 0.95; 0.81-1.12). There appears to be no increase in the risk of breast cancer associated with current smoking in BRCA1 or BRCA2 carriers. There is a possibility of an increased risk of breast cancer among BRCA1 carriers associated with past smoking. There may be different effects of carcinogens in BRCA mutation carriers, depending upon the timing of exposure.

Breast Cancer Incidence and the Effect of Cigarette Smoking in Heterozygous Carriers of Mutations in the Ataxia-Telangiectasia Gene

“…Some previous studies of links between cigarette smoking and breast cancer in both the general population or in any genetically defined subpopulation such as BRCA1/2 mutation carriers have found modest evidence for an association whereas others have found little or no such evidence (20)(21)(22)(23)(24)(25)(26)(27). Terry et al (21) reviewed reports through 2002, with most studies finding little or no increase in breast cancer risk associated with smoking, whereas others reported relative risks ranging from 0.8 to 2.9 in studies with varying numbers of subjects and statistical power.…”

“…Later studies were equally conflicting, with some finding no association of smoking with increased breast cancer risk (20,(22)(23)(24) whereas others reported relative risks of breast cancer between smokers and nonsmokers ranging from 1.1 to 1.5 (25,26). Among BRCA1/2 carriers, previous studies are also conflicting; one study estimated the relative risk of breast cancer at 1.3 (27), whereas another determined that smoking did not increase the breast cancer risk among carriers (28).…”

Modifiers of breast and ovarian cancer risks for BRCA1 and BRCA2 mutation carriers

“…Findings for BRCA1 mutation carriers in relation to oral contraceptive use and smoking have been inconsistent (Brunet et al 1998, Colilla et al 2006, Haile et al 2006, Breast Cancer Family Registry 2008, Ginsburg et al 2009, Bernholtz et al 2011, Lecarpentier et al 2011), even 23:10 within reports from the same research groups (Brunet et al 1998, Gronwald et al 2006a, Ginsburg et al 2009). For BRCA2 mutation carriers, published evidence is more consistent with oral contraceptive use being associated with an increased risk of breast cancer (Haile et al 2006, Bernholtz et al 2011.…”

Variation in breast cancer risk with mutation position, smoking, alcohol, and chest X-ray history, in the French National BRCA1/2 carrier cohort (GENEPSO)

“…The effect of alcohol among BRCA1/2 carriers has been investigated in only two studies [2,3]. Studies on the effect of smoking on BC in BRCA mutation carriers have also yielded different results [4][5][6][7][8][9][10]. Among studies of the effect of exposure to low-dose radiation during mammography or chest X-ray [11][12][13][14][15], two show a significantly increased risk of BC [11,12].…”