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.1996.03540180050032
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发表时间：
1996-11
期刊：
影响因子：
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通讯作者：
C. Ambrosone;J. Freudenheim;S. Graham;J. Marshall;J. Vena;J. Brasure;A. Michalek;R. Laughlin;Takuma Nemoto;K. Gillenwater;A. M. Harrington;P. Shields
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文献类型：
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作者：
C. Ambrosone;J. Freudenheim;S. Graham;J. Marshall;J. Vena;J. Brasure;A. Michalek;R. Laughlin;Takuma Nemoto;K. Gillenwater;A. M. Harrington;P. Shields
目的研究n -乙酰基转移酶2 （NAT2）多态性是否导致香烟烟雾中致癌芳香胺解毒能力下降，从而使一些吸烟女性更容易患乳腺癌。设计采用遗传分析的病例对照研究。对占白人慢乙酰化表型90% ~ 95%的3个多态性进行了DNA分析。背景和参与者：发生原发性乳腺癌的白人女性（304例）和社区对照（327例）。结果：吸烟和NAT2状态均与乳腺癌风险无关。在绝经前妇女中，没有明确的模式表明吸烟与NAT2状态有关。在绝经后妇女中，NAT2强烈地改变了吸烟与风险的关系。对于缓慢乙酰化者，当前吸烟和过去吸烟以剂量依赖的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]）。在快速乙酰化患者中，吸烟与乳腺癌风险增加无关。结论：我们的研究结果表明，吸烟可能是缓慢乙酰化的绝经后妇女患乳腺癌的重要危险因素，对致癌物质暴露的反应具有异质性，这可以解释之前吸烟作为乳腺癌危险因素的不一致发现。
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.