Null Genotypes of GSTM1 and GSTT1 Contribute to Risk of Cervical Neoplasia: An Evidence-Based Meta-Analysis

Abstract

Background and ObjectivesGlutathione S-transferases (GSTs) are multifunctional enzymes that play a key role in the detoxification of varieties of both endogenous products of oxidative stress and exogenous carcinogens.MethodsIn this meta-analysis, twenty-five studies were identified by searching PubMed, EMBASE, ISI Web of Science and CBM databases: 23 evaluated GSTM1 and 19 evaluated GSTT1. Crude odds ratios with corresponding 95% confidence intervals were used to estimate the association between GSTM1 and GSTT1 polymorphisms and risk of cervical neoplasia. Subgroup analyses were conducted by pathological history, ethnicity, source of DNA for genotyping, quality score, and matching variable.ResultsThe null genotypes of GSTM1 and GSTT1 polymorphisms were associated with a significantly increased risk of cervical neoplasia (for GSTM1: OR = 1.40; 95%CI, 1.19–1.65; for GSTT1: OR = 1.30; 95%CI, 1.05–1.62, respectively). Subgroup analyses showed that the null genotype of GSTM1 increased the risk of cervical neoplasia in Asians, studies with DNA isolation from white blood cells and tissue samples, both high and low quality studies, and matched studies. In GSTM1-GSTT1 interaction analysis, individuals with dual null genotype were associated with a significantly increased risk of cervical neoplasia (OR = 1.72; 95%CI, 1.18–2.51).ConclusionThese findings indicate that GSTM1 and GSTT1 polymorphisms, particularly GSTM1-GSTT1 interaction, may play critical roles in the development of cervical neoplasia. A conservative manner should be adopted to interpret these results because of obvious heterogeneity between-study, unadjusted data, and relatively small sample size in this meta-analysis. Well designed studies with larger sample size are of great value to confirm these results.

Genetic polymorphisms of glutathione S transferase and cervical intraepithelial neoplasia

“…Overall, null genotypes of GSTM1 and GSTT1 genes are not associated with cervical cancer and precancerous lesions. The results are concordant with other previous studies (32,33).…”

Meta-analysis of GSTM1 and GSTT1 Polymorphisms and Risk of Nasopharyngeal Cancer

“…These include meta-analyses that suggest GSTM1 deficiency increases the risk of head and neck cancer (Hashibe et al, 2003;Ye et al, 2004;Tripathy and Roy, 2006), cervical cancers (Gao et al, 2011;Liu and Xu, 2012) and oral cancer ). However, a number of meta-analyses indicated no marked association of GSTM1 null mutations with hepatocellular cancer (White et al, 2008), brain tumours (Sima et al, 2012), colorectal cancers (Zhao et al, 2012), ovarian cancers (Economopoulos et al, 2010), melanoma (Nie et al, 2011).…”

“…Null genotype of GSTT1 has been suggested to associate with risks of number of cancers. Marked association of GSTT1 deletion with lung cancer (Hosgood et al, 2007), gastric cancer (Saadat, 2006), leukaemia (Ye and Song, 2005), cervical cancers (Gao et al, 2011), breast cancer , bladder cancer (Gong et al, 2012) and head and neck cancer (Hashibe et al, 2003) has been demonstrated. In this study, the results indicate that null GSTT1 genotype might increase susceptibility to NPC which was not in line with evidence-based meta-analysis of pertaining to GSTM1 and GSTT1 polymorphisms on nasopharyngeal cancer as the latter indicated no association.…”

Association of the p53 or GSTM1 polymorphism with the risk of nasopharyngeal carcinoma: A meta-analysis

“…Additionally, there are certain previous studies investigating the association between the p53/GSTM1 gene polymorphisms and neoplasms, including oral, cervical and hepatocellular cancer. Certain results are positive, while others are negative (35)(36)(37)(38)(39)(40). Therefore, the association between the p53/GSTM1 gene polymorphisms and NPC risk remains to be elucidated.…”