ATAAA repeat upstream of glutathione S-transferase P1 and prostate cancer risk
ATAAA repeat upstream of glutathione S-transferase P1 and prostate cancer risk
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DOI：
10.1016/s0090-4295(01)01498-4
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发表时间：
2002-01-01
期刊：
影响因子：
2.1
通讯作者：
Giovannucci, E
中科院分区：
文献类型：
--
作者：
Platz, EA;Krithivas, K;Giovannucci, E
目标。谷胱甘肽S转移酶p1是一种解毒酶，也与类固醇激素结合，在人前列腺癌中的表达减弱或缺失，可能是由于启动子的高甲基化。其启动子的上游是一个功能意义未知的多态ATAAA重复序列。我们评估了该基因多态是否与前列腺癌相关。在医生健康研究的参与者中确定了前列腺癌发病病例(n=186)和对照组(n=398)。从外周全血中提取DNA，用荧光标记的引物扩增包含重复序列的区域。这些片段在聚丙烯酰胺凝胶上运行，并通过Genescan软件进行大小调整。等位基因用聚合酶链式反应片段大小表示。我们从控制年龄和吸烟状况的Logistic回归模型中估计了GSTP1基因、ATAAA等位基因和基因型与前列腺癌的相对风险。共检测到15个GSTP1 ATAAA等位基因，其中C(19个重复)、G(21个重复)和1个(22个重复)在对照组中占80%。与C组相比，G组和C组患前列腺癌的相对危险度分别为1.1(95%可信区间0.7~1.7)和0.8(95%可信区间0.6~1.2)。较少见的等位基因患前列腺癌的相对危险度也没有显著增加。与最常见的CC基因相比，其他基因类型似乎都不会增加患前列腺癌的风险。这项研究的结果不支持GSTP1启动子上游的ATAAA重复多态在前列腺癌发病中的重要作用。泌尿外科59：159-164,2002。(C)2002年，爱思唯尔科学公司。
Objectives. Expression of glutathione S-transferase pi (GSTP1), a detoxification enzyme that also binds steroid hormones, is diminished or absent in human prostate tumors possibly because of promoter hypermethylation. Upstream of its promoter is a polymorphic ATAAA repeat of unknown functional significance. We evaluated whether this polymorphism is associated with prostate cancer.Methods. Incident prostate cancer cases (n=186) and controls (n=398) were identified among participants in the Physicians' Health Study. DNA was extracted from peripheral whole blood, and the region encompassing the repeat was amplified using fluorescent-labeled primers. The fragments were run on polyacrylamide gels and sized by Genescan software. Alleles were designated by polymerase chain reaction fragment size. We estimated the relative risk of prostate cancer for the GSTP1 gene ATAAA alleles and genotype from logistic regression models controlling for age and cigarette smoking status.Results. Fifteen GSTP1 ATAAA alleles were observed; C (19 repeats), G (21 repeats), and 1 (22 repeats) accounted for 80% among the controls. Compared with C, the relative risks for prostate cancer were I. 1 (95% confidence interval 0.7 to 1.7) for G and 0.8 (95% confidence interval 0.6 to 1.2) for 1. The relative risks were also not statistically significantly elevated for the less common alleles. Compared with CC, the most common genotype, none of the other genotypes appeared to be associated with an increased risk of prostate cancer.Conclusions. The results of this study do not support an important role of the ATAAA repeat polymorphism upstream from the GSTP1 promoter in prostate cancer incidence. Urology 59: 159-164, 2002. (C) 2002, Elsevier Science Inc.