A PROSPECTIVE-STUDY OF NAT2 ACETYLATION GENOTYPE, CIGARETTE-SMOKING, AND RISK OF BREAST-CANCER

Polymorphisms in the N-acetyltransferase 2 (NAT2) gene are determinant s of the rate of metabolic activation of carcinogenic compounds such a s aryl aromatic amines, Homozygosity for any combination of three vari ant alleles in Caucasians defines 'slow' acetylators; presence of one or two wild-type alleles characterizes 'rapid' acetylators, Although m ost previous studies have not observed an overall elevation in risk of breast cancer among slow acetylators, a recent study observed that ci garette smoking was associated with a large increase in risk of breast cancer among slow acetylators. We assessed the relation between NAT2 acetylation status and breast cancer risk, and its interaction with sm oking, in a prospective study of mainly Caucasian US women, Four hundr ed and sixty-six incident cases who were diagnosed with breast cancer after giving a blood specimen in 1989-90 were matched to 466 controls in a nested case-control study, NAT2 genotype was determined using PCR -RFLP assays. The multivariate relative risk (RR) comparing slow with rapid acetylators was 0.9 (95 % CI 0.7-1.2), Among slow acetylators, c urrent smoking immediately prior to diagnosis was not associated with a significant elevation in risk compared with never smoking rapid acet ylators (RR 1.4, 95 % CI 0.7-2.6), No significant association was seen between pack-years of smoking and risk of breast cancer among either slow or fast acetylators, A non-significant elevation in risk was obse rved among women who smoked for greater than or equal to 5 years prior to first pregnancy and were rapid acetylators, compared with never sm oking rapid acetylators (RR = 1.5, 95% CI 0.9-2.6). In analyses limite d to 706 post-menopausal women, the elevated risks for current smokers immediately prior to diagnosis who were slow acetylators compared wit h never smokers who were fast acetylators were slightly stronger but s till not statistically significant, In summary, we observed little evi dence of an association between NAT2 genotype and breast cancer, In th is prospective study, cigarette smoking was not appreciably associated with breast cancer among either slow or fast NAT2 acetylators.