Ambrosone C B, Freudenheim J L, Graham S, Marshall J R, Vena J E, Brasure J R, Michalek A M, Laughlin R, Nemoto T, Gillenwater K A, Shields P G
National Center for Toxicological Research, Division of Molecular Epidemiology, Jefferson, Ark. 72079, USA.
JAMA. 1996 Nov 13;276(18):1494-501.
To determine if N-acetyltransferase 2 (NAT2) polymorphisms result in decreased capacity to detoxify carcinogenic aromatic amines in cigarette smoke, thus making some women who smoke more susceptible to breast cancer.
Case-control study with genetic analyses. DNA analyses were performed for 3 polymorphisms accounting for 90% to 95% of the slow acetylation phenotype among whites.
White women with incident primary breast cancer (n=304) and community controls (n=327).
Neither smoking nor NAT2 status was independently associated with breast cancer risk. There were no clear patterns of increased risk associated with smoking by NAT2 status among premenopausal women. In postmenopausal women, NAT2 strongly modified the association of smoking with risk. For slow acetylators, current smoking and smoking in the distant past increased breast cancer risk in a dose-dependent manner (odds ratios [95% confidence intervals] for the highest quartile of cigarettes smoked 2 and 20 years previously, 4.4 [1.3-14.8] and 3.9 [1.4-10.8], respectively). Among rapid acetylators, smoking was not associated with increased breast cancer risk.
Our results suggest that smoking may be an important risk factor for breast cancer among postmenopausal women who are slow acetylators, demonstrate heterogeneity in response to carcinogenic exposures, and may explain previous inconsistent findings for cigarette smoking as a breast cancer risk factor.
确定N - 乙酰基转移酶2（NAT2）基因多态性是否会导致对香烟烟雾中致癌芳香胺的解毒能力下降，从而使一些吸烟女性更易患乳腺癌。
采用基因分析的病例对照研究。对白人中占慢乙酰化表型90%至95%的3种多态性进行DNA分析。
新发原发性乳腺癌的白人女性（n = 304）和社区对照者（n = 327）。
吸烟和NAT2状态均与乳腺癌风险无独立关联。绝经前女性中，未发现按NAT2状态划分的与吸烟相关的风险增加的明确模式。在绝经后女性中，NAT2强烈改变了吸烟与风险的关联。对于慢乙酰化者，当前吸烟和过去长期吸烟以剂量依赖方式增加乳腺癌风险（分别针对2年和20年前吸烟量最高四分位数的优势比[95%置信区间]为4.4[1.3 - 14.8]和3.9[1.4 - 10.8]）。在快乙酰化者中，吸烟与乳腺癌风险增加无关。
我们的结果表明，吸烟可能是慢乙酰化绝经后女性患乳腺癌的重要风险因素，证明了对致癌暴露反应的异质性，并可能解释先前关于吸烟作为乳腺癌风险因素的不一致研究结果。
