Meta-analysis of the Association Between GSTM1 and GSTT1 Gene Polymorphisms and Cervical Cancer

Zhen-Yong Zhang,Yao Xie,Shu-Juan Yang,Rong Wu,Xue-Ying Jin,Rui Xing,Li-Na Wu

doi:10.7314/apjcp.2012.13.3.815

Zhen-Yong Zhang, Yao Xie + Show 5 more

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https://doi.org/10.7314/apjcp.2012.13.3.815

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Abstract

We conducted a meta-analysis to analyze the influence of GSTM1 and GSTT1 gene polymorphisms on cervical cancer risk, and explore gene-environment interactions. Identification of relevant studies was carried out through a search of Medline and the EMbase up to Oct. 2011. All case-control studies that investigated the association between GSTM1 and GSTT1 gene polymorphisms and risk of cervical cancer were included. The pooled odds ratio (OR) was used for analyses of results and the corresponding 95% confidence intervals (CI) were estimated. A total of 21 case-control studies were included in the meta-analysis of GSTM1 (2,378 cases and 2,639 controls) and GSTT1 (1,229 cases and 1,223 controls) genotypes. The overall results showed that the GSTM1 null was related to an increased risk of cervical cancer (OR=1.50, 95% CI=1.21-1.85). Subgroup analysis were performed based on smoking and ethnicity. Our results showed that smokers with null GSTM1 genotype had a moderate increased risk of cervical cancer (OR=1.85, 95% CI=1.07-3.20). For the ethnicity stratification, moderate significantly increased risk of null GSTM1 genotype was found in Chinese (OR=2.12, 95% CI=1.43-3.15) and Indian populations (OR=2.07, 95% CI=1.49-2.88), but no increased risk was noted in others. This meta-analysis provided strong evidence that the GSTM1 genotype is associated with the development of cervical cancer, especially in smokers, and Chinese and Indian populations. However, no association was found for GSTT1 null genotype carriers.

Highlights

Cervical cancer is the third most common cancer in women, and the seventh overall, with an estimated 530,000 new cases in 2008
Our results showed that smokers with null GSTM1 genotype had a moderate increased risk of cervical cancer (OR=1.85, 95% confidence intervals (CI)=1.07-3.20)
Moderate significantly increased risk of null GSTM1 genotype was found in Chinese (OR=2.12, 95% CI=1.43-3.15) and Indian populations (OR=2.07, 95% CI=1.49-2.88), but no increased risk was noted in others

Summary

Introduction

Cervical cancer is the third most common cancer in women, and the seventh overall, with an estimated 530,000 new cases in 2008. Rates are lowest in Western Asia, Northern America and Australia/ New Zealand (ASRs less than 6 per 100,00) (IARC, 2011). The different incidence in different areas indicates the genetic factors and environmental factors play a role in the development of cervical cancer. There are other cofactors for cervical cancer development. Previous studies showed the glutathione S-transferases (GSTs) genetic variants is related to human phase II detoxification enzymes. Cytosolic GSTs (GSTM and GSTT) play a role in the detoxification of the carcinogenic electrophiles of aflatoxin and polycyclic aromatic hydrocarbons (PAHs) in tobacco smoke. Several studies found the association between the genetic polymorphisms of GSTs and the risk of cancer development (Carlsten et al, 2008; Mo et al, 2009; Zhuo et al, 2009)

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