An Updated Meta-Analysis: Cervical Cancer Risk Conferred by GSTM1 and GSTT1 Polymorphisms

Abstract

Objective: To study the influence of GSTM1 and GSTT1 gene polymorphisms on cervical cancer (CC) risk, and explore genetic-environmental interactions. Methods: After a systematic literature search, all relevant studies entailing the association between GST polymorphisms and CC were included. The pooled odds ratio (OR) was used for analysis of the results and corresponding 95% confidence intervals (CI) were estimated. Results: A total of 23 case-control studies were included in the meta-analysis of GSTM1 (2,250 CC cases and 3,025 controls) and GSTT1 (1,704 CC cases and 2,460 controls) genotypes. For the GSTM1 polymorphisms, the null genotype of GSTM1 was associated with an increased CC risk for the total population (OR=1.57, 95% CI=1.25-1.98). A similar association was found in China (OR=2.34, 95% CI=1.56-3.52), India (OR=2.02, 95% CI=1.43-2.83), Pakistan (OR=5.52, 95% CI=2.34-13.07), Serbia (OR=1.73, 95% CI=0.68-4.39) and Kazakhstan (OR=6.5, 95%CI=2.25-18.81), but was not noted for others countries. Regarding human papilloma virus (HPV) infection, moderately but significantly increased risk of the null GSTM1 genotype was found in HPV-positive patients (OR=2.59, 95% CI=1.57-4.27). For the GSTT1 polymorphisms, the null GSTT1 genotype was associated with increased CC risk in the total population (OR=1.44, 95% CI=1.07-1.93). Regarding ethnic stratification, a significantly increased risk of the null GSTT1 genotype was found in Kazakhstan (OR=3.99, and Brazil (OR=4.58, 95% CI=2.04-10.28). With respect to smoking, the two aspects of the analysis above were not significantly associated with CC risk in smokers or non-smokers, respectively. For the GSTM1/GSTT1 interaction analysis, the dual null genotypes of GSTM1/GSTT1 were significantly associated with increased CC risk for the total population (OR=1.62, 95% CI=1.14-2.29). Conclusion: This meta-analysis provided sufficient evidence that the null genotype of GSTM1, or GSTT1 and the dual-null genotypes of GSTM1/GSTT1 are associated with CC.