A prospective study of NAT2 acetylation genotype, cigarette smoking, and risk of breast cancer

Polymorphisms in the N-acetyltransferase 2 (NAT2) gene are determinants ofthe rate of metabolic activation of carcinogenic compounds such as arylaromatic amines. Homozygosity for any combination of three variant allelesin Caucasians defines 'slow' acetylators; presence of one or two wild-typealleles characterizes 'rapid' acetylators. Although most previous studieshave not observed an overall elevation in risk of breast cancer among slowacetylators, a recent study observed that cigarette smoking was associatedwith a large increase in risk of breast cancer among slow acetylators. Weassessed the relation between NAT2 acetylation status and breast cancerrisk, and its interaction with smoking, in a prospective study of mainlyCaucasian US women. Four hundred and sixty-six incident cases who werediagnosed with breast cancer after giving a blood specimen in 1989-90 werematched to 466 controls in a nested case-control study. NAT2 genotype wasdetermined using PCR-RFLP assays. The multivariate relative risk (RR)comparing slow with rapid acetylators was 0.9 (95% CI 0.7-1.2). Among slowacetylators, current smoking immediately prior to diagnosis was notassociated with a significant elevation in risk compared with never smokingrapid acetylators (RR = 1.4, 95% CI 0.7-2.6). No significant associationwas seen between pack-years of smoking and risk of breast cancer amongeither slow or fast acetylators. A non-significant elevation in risk wasobserved among women who smoked for > or = 5 years prior to firstpregnancy and were rapid acetylators, compared with never smoking rapidacetylators (RR = 1.5, 95% CI 0.9-2.6). In analyses limited to 706post-menopausal women, the elevated risks for current smokers immediatelyprior to diagnosis who were slow acetylators compared with never smokerswho were fast acetylators were slightly stronger but still notstatistically significant. In summary, we observed little evidence of anassociation between NAT2 genotype and breast cancer. In this prospectivestudy, cigarette smoking was not appreciably associated with breast canceramong either slow or fast NAT2 acetylators.