Cigarette smoking, N-acetyltransferase 2 genetic polymorphisms, and breast cancer risk
Cigarette smoking, N-acetyltransferase 2 genetic polymorphisms, and breast cancer risk
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DOI：
10.1001/jama.276.18.1494
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发表时间：
1996-11-13
影响因子：
120.7
通讯作者：
Shields, PG
中科院分区：
文献类型：
--
作者：
Ambrosone, CB;Freudenheim, JL;Shields, PG
客观。-确定N-乙酰转移酶2（NAT 2）多态性是否会导致香烟烟雾中致癌芳香胺解毒能力降低，从而使一些吸烟的女性更容易患乳腺癌。病例对照研究与遗传分析，DNA分析进行了3个多态性占90%至95%的慢乙酰化表型白人。设置和参与者。原发性乳腺癌的白色女性（n=304）和社区对照组（n=327）。吸烟和NAT 2状态均与乳腺癌风险无关。在绝经前妇女中，NAT 2状态与吸烟相关的风险增加没有明确的模式。在绝经后妇女中，NAT 2强烈改变了吸烟与风险的关联。对于慢乙酰化者，目前吸烟和过去吸烟以剂量依赖性方式增加乳腺癌风险（2年和20年前吸烟的最高四分位数的比值比[95%置信区间]分别为4.4 [1.3-14.8]和3.9 [1.4-10.8]）。在快速乙酰化者中，吸烟与乳腺癌风险增加无关。我们的研究结果表明，吸烟可能是乳腺癌的一个重要的危险因素，绝经后妇女谁是缓慢乙酰化，表现出异质性的致癌暴露，并可能解释以前不一致的结果吸烟作为乳腺癌的危险因素。
Objective.-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.Design.-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.Setting and Participants.-White women with incident primary breast cancer (n=304) and community controls (n=327).Results.-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.Conclusions.-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.