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谷胱甘肽 S-转移酶基因多态性(GSTM1、GSTT1、GSTP1)与前列腺癌:伊朗德黑兰的病例对照研究。

Glutathione S-transferase gene polymorphisms (GSTM1, GSTT1, GSTP1) and prostate cancer: a case-control study in Tehran, Iran.

出版信息

Prostate Cancer Prostatic Dis. 2011 Jun;14(2):105-13. doi: 10.1038/pcan.2010.54. Epub 2011 Jan 18.

Abstract

We evaluated the relationship between polymorphisms in the glutathione S-transferases (GSTs) GSTM1, GSTT1 and GSTP1 genes and prostate cancer (PCa). PCR-restriction fragment length polymorphism assay was used to genotype the GSTM1, GSTT1, and GSTP1 polymorphisms in 168 PCa cases and 336 frequency matched controls. The GSTM1 null, and GSTT1 null genotypes were associated with an increased odds ratio (OR) for PCa (OR=3.28, 95% confidence interval (CI): 2.47-5.64; P=0.005, and OR=3.21, 95% CI: 2.52-5.64; P=0.005, respectively) (Pcorrected=0.0062). The frequency of GSTP1 Val/Val genotype was 14.3% in cases compared with 2.4% in controls, this polymorphism thus being associated with a significantly increased risk of PCa (OR=3.72, 95% CI: 1.67-5.65; P=0.002). The risk associated with the concurrent absence of both of the genes (OR=4.8, 95% CI: 2.34-6.78) was greater than the product of risk in men with either null (OR=1.52, 95% CI: 0.82-2.31) genotype combinations (P=0.001, Pcorrected=0.0045). The combination of GSTP1 Ile/Val or Val/Val polymorphism with the GSTT1 null and GSTM1 null type resulted in an OR of 6.21 (95% CI: 4.83-16.87) (P=0.0001, Pcorrected=0.0062). A higher frequency of the GSTM1 null genotype and GSTT1 null genotype was observed in patients with Gleason score >7, with an OR for GSTM1 null 4.67 (95% CI: 3.64-7.62; P=0.001) and with an OR for GSTT1 null 3.62 (95% CI: 2.31-5.74; P=0.004). The results obtained demonstrated that simultaneous presence of three potentially risk alleles (GSTM1 null, GSTT1 null and GSTP1 Val) lead to a significant OR increase for PCa.

摘要

我们评估了谷胱甘肽 S-转移酶(GSTs)GSTM1、GSTT1 和 GSTP1 基因多态性与前列腺癌(PCa)之间的关系。采用 PCR-限制性片段长度多态性分析方法对 168 例 PCa 病例和 336 例频率匹配对照的 GSTM1、GSTT1 和 GSTP1 多态性进行基因分型。GSTM1 缺失型和 GSTT1 缺失型基因型与 PCa 的比值比(OR)增加相关(OR=3.28,95%置信区间(CI):2.47-5.64;P=0.005,和 OR=3.21,95% CI:2.52-5.64;P=0.005)(Pcorrected=0.0062)。病例组 GSTP1 Val/Val 基因型的频率为 14.3%,而对照组为 2.4%,因此该多态性与 PCa 的风险显著增加相关(OR=3.72,95% CI:1.67-5.65;P=0.002)。同时缺失两种基因(OR=4.8,95% CI:2.34-6.78)的风险大于具有任何一种缺失(OR=1.52,95% CI:0.82-2.31)基因型组合的风险(P=0.001,Pcorrected=0.0045)。GSTP1 Ile/Val 或 Val/Val 多态性与 GSTT1 缺失和 GSTM1 缺失类型的组合导致 OR 为 6.21(95% CI:4.83-16.87)(P=0.0001,Pcorrected=0.0062)。Gleason 评分>7 的患者中观察到 GSTM1 缺失基因型和 GSTT1 缺失基因型的频率更高,GSTM1 缺失的 OR 为 4.67(95% CI:3.64-7.62;P=0.001),GSTT1 缺失的 OR 为 3.62(95% CI:2.31-5.74;P=0.004)。研究结果表明,同时存在三种潜在风险等位基因(GSTM1 缺失、GSTT1 缺失和 GSTP1 Val)可导致 PCa 的比值比显著增加。

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