Cigarette smoking, cytochrome P450 1A1 polymorphisms, and breast cancer risk in the Nurses' Health Study.
Cigarette smoking, cytochrome P450 1A1 polymorphisms, and breast cancer risk in the Nurses' Health Study.
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发表时间：
1998-02
期刊：
影响因子：
11.2
通讯作者：
N. Ishibe;S. Hankinson;G. Colditz;D. Spiegelman;W. Willett;F. Speizer;K. Kelsey;D. Hunter
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文献类型：
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作者：
N. Ishibe;S. Hankinson;G. Colditz;D. Spiegelman;W. Willett;F. Speizer;K. Kelsey;D. Hunter
环境暴露于致癌物可能导致乳腺癌发病率增加和美国乳腺癌发病率的地理差异。受到广泛关注的一类化学品是多环芳烃，它在环境中无处不在，并存在于香烟烟雾中。细胞色素P450 1A 1（CYP 1A 1）基因编码一种酶，该酶有助于芳烃羟化酶活性，该酶参与多环芳烃的代谢。CYP 1A 1的基因型变异与芳烃羟化酶活性增加有关，一些流行病学研究表明，具有变异基因型的女性患乳腺癌的风险增加。我们前瞻性地评估了CYP 1A 1多态性与乳腺癌风险之间的关系，以及吸烟对这些关系的潜在影响，这是一项嵌套在护士健康研究中的病例对照研究。我们采用PCR-RFLP方法对466例乳腺癌患者和466例正常对照者的CYP 1A 1基因第6235位核苷酸（MspI）的T → C转换和第4889位核苷酸（外显子7）的A → G转换进行了分析。相对风险（RR）和95%置信区间（CI）用于量化至少有一个变异等位基因的受试者相对于野生型等位基因纯合子的受试者患乳腺癌的风险，使用条件logistic回归。CYP 1A 1基因型变异的乳腺癌风险总体上没有明显增加（RR（MspI），1.05; 95% CI，0.74-1.50和RR（外显子7），0.88; 95% CI，0.58-1.33）。然而，在18岁之前开始吸烟且具有CYP 1A 1-MspI变异基因型的女性中观察到乳腺癌风险提示性增加，与该多态性纯合野生型的非吸烟者相比（RR，5.65; 95%CI，1.50-21.3;所有乳腺癌病例中归因于该风险因素的百分比，2.5%）。外显子7多态性也观察到类似的基因-环境相关性（RR，3.61; 95%CI，1.11-11.7;所有乳腺癌病例中归因于该风险因素的百分比，2.2%）。这些数据与生命早期吸烟是遗传易感妇女亚群中乳腺癌的可改变原因的假设是一致的。然而，在具有CYP 1A 1多态性变异形式的高加索女性中，年轻时吸烟导致的乳腺癌的比例较低。
Environmental exposure to carcinogens may contribute to increasing breast cancer rates and geographic variation in breast cancer incidence in the United States. One class of chemicals that has received much attention are the polyaromatic hydrocarbons that are ubiquitous in the environment and occur in cigarette smoke. The cytochrome P450 1A1 (CYP1A1) gene codes for an enzyme that contributes to aryl hydrocarbon hydroxylase activity, which is involved in the metabolism of polyaromatic hydrocarbons. Genotypic variants of CYP1A1 have been associated with increased aryl hydrocarbon hydroxylase activity, and some epidemiological studies suggest that women with the variant genotype(s) are at increased risk for breast cancer. We prospectively evaluated the associations between the CYP1A1 polymorphisms and breast cancer risk, as well as the potential modification of these associations by cigarette smoking, in a case-control study nested within the Nurses' Health Study. We analyzed the T-->C transition at nucleotide 6235 (MspI) and the A-->G transition at nucleotide 4889 (exon 7) in CYP1A1 by PCR-RFLP assays among 466 incident breast cancer cases and 466 matched controls. Relative risks (RRs) and 95% confidence intervals (CIs) were used to quantify the risk of breast cancer among subjects who had at least one variant allele relative to subjects who were homozygous for the wild-type allele, using conditional logistic regression. No overall increase in breast cancer risk with the variant CYP1A1 genotypes was apparent (RR(MspI), 1.05; 95% CI, 0.74-1.50 and RR(exon7), 0.88; 95% CI, 0.58-1.33). However, a suggestive increase in breast cancer risk was observed among women who had commenced smoking before the age of 18 and had the CYP1A1-MspI variant genotype compared to nonsmokers who were homozygous wild type for the polymorphism (RR, 5.65; 95% CI, 1.50-21.3; percentage of all breast cancer cases attributable to this risk factor, 2.5%). A similar gene-environment association was observed for the exon 7 polymorphism (RR, 3.61; 95% CI, 1.11-11.7; percentage of all breast cancer cases attributable to this risk factor, 2.2%). These data are compatible with the hypothesis that cigarette smoking early in life is a modifiable cause of breast cancer in a subpopulation of genetically susceptible women. However, the proportion of breast cancer attributable to cigarette smoking at a young age among Caucasian women with the variant form of the CYP1A1 polymorphisms is low.