A prospective study of NAT2 acetylation genotype, cigarette smoking, and risk of breast cancer
| AUTHOR: | Hunter DJ; Hankinson SE; Hough H; Gertig
DM;
Garcia-Closas M; Spiegelman D; Manson JE; Colditz GA; Willett WC; Speizer FE; Kelsey K |
| AUTHOR AFFILIATION: | Department of Medicine,
Brigham
and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. |
| SOURCE: | Carcinogenesis 1997
Nov;18(11):2127-32 |
| CITATION IDS: | PMID: 9395212 UI: 98055590 |
| ABSTRACT: | Polymorphisms in the N-acetyltransferase
2
(NAT2) gene are determinants of the rate of metabolic activation of carcinogenic compounds such as aryl aromatic amines. Homozygosity for
any combination of three variant alleles in Caucasians defines 'slow' acetylators; presence of one or two wild-type alleles characterizes 'rapid'
acetylators. Although most previous studies have not observed an overall elevation in risk of breast cancer among slow acetylators, a recent
study observed that cigarette 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 smoking, in a prospective study of mainly Caucasian
US women. Four hundred 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, current smoking immediately prior to diagnosis
was not associated with a significant elevation in risk compared with never smoking rapid acetylators (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 observed among women who smoked for > or = 5 years prior to first pregnancy and were rapid acetylators, compared
with never smoking rapid acetylators (RR = 1.5, 95% CI 0.9-2.6). In analyses limited to 706 post-menopausal women, the elevated risks for
current smokers immediately prior to diagnosis who were slow acetylators compared with never smokers who were fast acetylators were slightly
stronger but still not statistically significant. In summary, we observed little evidence of an association between NAT2 genotype and breast
cancer. In this prospective study, cigarette smoking was not appreciably associated with breast cancer among either slow or fast NAT2
acetylators. |
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