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常见的 GSTM1、GSTT1、GSTP1、GSTA1 多态性与中欧人群结直肠癌易感性的关系。

Common polymorphisms in GSTM1, GSTT1, GSTP1, GSTA1 and susceptibility to colorectal cancer in the Central European population.

机构信息

Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Brno, Czech Republic.

出版信息

Eur J Med Res. 2012 Jun 14;17(1):17. doi: 10.1186/2047-783X-17-17.

Abstract

BACKGROUND

Central Europe presents with the highest incidence of sporadic colorectal cancer (CRC) worldwide. As sporadic CRC represents a typical multifactorial disease, it is characterized by intense interaction of the genetic background with the environment. Glutathione S-transferases could act as attractive susceptibility genes for CRC, as they are directly involved in conjugation between glutathione and chemotherapeutics, environmental pollutants and a wide spectrum of xenobiotics.

METHODS

In this study, we investigated associations of polymorphisms in glutathione S-transferases (GSTs) genes, that is GSTA1, GSTT1, GSTM1 and GSTP1, with CRC in a total of 197 cases and 218 controls originating from the Czech Central European population. Polymorphisms were assessed by polymerase chain reaction/restriction fragment length polymorphism-based methods, allele-specific multiplex and allelic discrimination by real-time polymerase chain reaction.

RESULTS

None of investigated polymorphisms showed any associations with CRC, with the exception of GSTP1; where the heterozygote genotype Ile105Val was associated with decreased risk of CRC (P = 0.043).

CONCLUSIONS

The frequencies observed in our study are in accordance with those from other European Caucasian populations. Based on our studies, examined variability in GST genes is not a major determinant of CRC susceptibility in the Central European population.

摘要

背景

中欧地区的散发性结直肠癌(CRC)发病率居世界首位。由于散发性 CRC 是一种典型的多因素疾病,其特征是遗传背景与环境之间的强烈相互作用。谷胱甘肽 S-转移酶(GSTs)可能作为 CRC 的易感基因,因为它们直接参与谷胱甘肽与化疗药物、环境污染物和广泛的外源性物质之间的结合。

方法

本研究共纳入 197 例 CRC 患者和 218 例来自捷克中欧人群的对照,采用聚合酶链反应/限制性片段长度多态性(PCR/RFLP)、等位基因特异性多重 PCR 和实时 PCR 等位基因鉴别方法,检测 GSTs 基因(GSTA1、GSTT1、GSTM1 和 GSTP1)的多态性。

结果

除 GSTP1 外,未发现其他任何多态性与 CRC 相关,其中 GSTP1 的 Ile105Val 杂合基因型与 CRC 风险降低相关(P = 0.043)。

结论

本研究中的 GST 基因多态性频率与其他欧洲白种人群一致。基于本研究,GST 基因的变异性不是中欧人群 CRC 易感性的主要决定因素。

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