Association of the Glutathione S-Transferase M1, T1 Polymorphisms with Cancer: Evidence from a Meta-Analysis

Jianzheng Fang,Xinnong Liu,Bianjiang Liu,Yunfei Deng,Jinbao Gu,Yi Zhang,Jian Qian,Pengchao Li,Hainan Wang,Shifeng Su,Zengjun Wang,Hongqing Cui,Zhen Song,Shengli Zhang,Rui Zhang,Shangqian Wang,N Charlotte Onland-Moret

doi:10.1371/journal.pone.0078707

Jianzheng Fang, Xinnong Liu + Show 15 more

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https://doi.org/10.1371/journal.pone.0078707

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Abstract

BackgroundGlutathione S-transferases (GSTs) are a family of multifunctional enzymes that are involved in the metabolism of many xenobiotics, including a wide range of environmental carcinogens. While the null genotypes in GSTM1 and GSTT1 have been implicated in tumorigenesis, it remains inconsistent and inconclusive. Herein, we aimed to assess the possible associations of the GSTM1 and GSTT1 null genotype in cancer risks.MethodsA meta-analysis based on 506 case-control studies was performed. Odds ratios (OR) with corresponding 95% confidence intervals (CIs) were used to assess the association.ResultsThe null genotypes of GSTM1 and GSTT1 polymorphisms were associated with a significantly increased risk in cancer (for GSTM1: OR = 1.17; 95%CI = 1.14–1.21; for GSTT1: OR = 1.16; 95%CI = 1.11–1.21, respectively). When the analysis was performed based on their smoking history, the risk associated of GSTM1 null and GSTT1 null genotypes with cancer is further increased (for GSTM1: OR = 2.66; 95%CI = 2.19–3.24; for GSTT1: OR = 2.46; 95%CI = 1.83–3.32, respectively).ConclusionsThese findings indicate that GSTM1 and GSTT1 polymorphisms may play critical roles in the development of cancer, especially in smokers.

Highlights

Glutathione S-transferases (GSTs) are a superfamily of phase II drug-metabolizing enzymes that are involved in the metabolism of many xenobiotics, including a variety of environmental carcinogens by catalyzing the conjugation of glutathione to electrophilic compounds [1]
Previous studies showed that a homozygous deletion or null genotype, at either the GSTM1 locus or the GSTT1 locus resulted in enzyme function loss, and it was hypothesized to be related to the susceptibility to cancer [1,3]
The risks (ORs) of cancer associated with the GSTM1 or GSTT1 polymorphism were estimated for each study

Summary

Introduction

Glutathione S-transferases (GSTs) are a superfamily of phase II drug-metabolizing enzymes that are involved in the metabolism of many xenobiotics, including a variety of environmental carcinogens by catalyzing the conjugation of glutathione to electrophilic compounds [1]. Previous studies showed that a homozygous deletion or null genotype, at either the GSTM1 locus or the GSTT1 locus resulted in enzyme function loss, and it was hypothesized to be related to the susceptibility to cancer [1,3]. GSTM1 and GSTT1 genes have a common variant of homozygous deletion (null genotype), which increases vulnerability to cytogenetic damage [4]. An increasing number of studies have investigated the association between GSTM1 or GSTT1 polymorphisms and cancer risk in human. Given the biological function of GSTs, many epidemiological studies have focused on the association of GSTM1 and GSTT1 polymorphisms with cancer risk in human. We aimed to assess the possible associations of the GSTM1 and GSTT1 null genotype in cancer risks

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