title: N-acetyltransferase 2 (NAT2) genotypes, cigarette smoking, and the risk of breast cancer.
abstract: N-acetyltransferases (NATs) are important catalytic enzymes that metabolize carcinogenic arylamines. NAT2 genotype might modify the role of cigarette smoking, a source of arylamine exposure, in breast cancer. We conducted a nested case-control study to investigate the association between NAT2 genotype, smoking and breast cancer risk among women (110 cases, 113 matched controls) from the CLUE II cohort in Washington County, MD. Compared to women with the slow acetylator genotype, the main effects odds ratios (OR) for NAT2 were 1.4 for the intermediate acetylator genotype (95% confidence limits (CL) 0.7, 2.7) and 3.6 for the homozygous rapid acetylator genotype (95% CL 1.1, 11.4) (P for trend = 0.05). Smoking was associated in the direction of increased breast cancer risk in slow acetylators (e.g., >15 pack-years versus never smokers OR 2.0; 95% CL 0.7, 5.8) but not in rapid acetylators. These associations were not statistically significant in the total study population, but a statistically significant interaction between smoking and NAT2 acetylator status was present in postmenopausal women. The main effect of NAT2 in the direction of increased risk suggests that exposures to NAT2-activated carcinogens other than cigarette smoke may be important in this study population. The results for smoking were consistent with an inactivation role for NAT2 in breast cancer.
authors.affiliation: Department of Epidemiology, Room E6132B, The Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD 21205, USA. aalberg@jhsph.edu
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Alberg
authors.forename: Alexander
authors.initials: A
authors.lastname: Daudt
authors.forename: Han-Yao
authors.initials: HY
authors.lastname: Huang
authors.forename: Sandra C
authors.initials: SC
authors.lastname: Hoffman
authors.forename: George W
authors.initials: GW
authors.lastname: Comstock
authors.forename: Kathy J
authors.initials: KJ
authors.lastname: Helzlsouer
authors.forename: Paul T
authors.initials: PT
authors.lastname: Strickland
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Bell
mesh_terms: D000328:Adult; D017677:Age Distribution; D000368:Aged; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015994:Incidence; D016015:Logistic Models; D008875:Middle Aged; D015999:Multivariate Analysis; D011110:Polymorphism, Genetic; D011336:Probability; D011379:Prognosis; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*; D016019:Survival Analysis
chemical_list: D001191:Arylamine N-Acetyltransferase