Abstract
Glutathione S-transferases (GSTs) are multifunctional enzymes that play a crucial role in the detoxification of both the endogenous products of oxidative stress and exogenous carcinogens. Recent studies investigating the association between genetic polymorphisms in GSTs and the risk of adult brain tumors have reported conflicting results. The rationale of this pooled analysis was to determine whether the presence of a GST variant increases adult glioma susceptibility by combining data from multiple studies. In our meta-analysis, 12 studies were identified by a search of the MEDLINE, HIGHWIRE, SCIENCEDIRECT and EMBASE databases. Of those 12, 11 evaluated GSTM1, nine evaluated GSTT1 and seven evaluated GSTP1 Ile105Val. Between-study heterogeneity was assessed using χ2-based Q statistic and the I2 statistic. Crude odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were used to estimate the association between GSTM1, GSTT1 and GSTP1 polymorphisms and the risk of adult gliomas. The quantitative synthesis showed no significant evidence to indicate an association exists between the presence of a GSTM1, GSTT1 or GSTP1 Ile105Val haplotype polymorphism and the risk of adult gliomas (OR, 1.008, 1.246, 1.061 respectively; 95% CI, 0.901-1.129, 0.963-1.611, 0.653-1.724 respectively). Overall, this study did not suggest any strong relationship between GST variants or related enzyme polymorphisms and an increased risk of adult gliomas. Some caveats include absence of specific raw information on ethnic groups or smoking history on glioma cases in published articles; therefore, well-designed studies with a clear stratified analysis on potential confounding factors are needed to confirm these results.
Highlights
Gliomas are the most common form of primary brain neoplasms in adults, with the major histopathological classifications being oligodendroglioma, astrocytoma and glioblastoma multiforme, among several other subtypes
The quantitative synthesis showed no significant evidence to indicate an association exists between the presence of a GSTM1, GSTT1 or GSTP1 Ile105Val haplotype polymorphism and the risk of adult gliomas (OR, 1.008, 1.246, 1.061 respectively; 95% confidence intervals (CIs), 0.901-1.129, 0.963-1.611, 0.653-1.724 respectively)
We found no apparent evidence of an association of the GSTP1 Ile105Val polymorphism with an increased risk of glioma in the subjects of seven studies
Summary
Gliomas are the most common form of primary brain neoplasms in adults, with the major histopathological classifications being oligodendroglioma, astrocytoma and glioblastoma multiforme, among several other subtypes. A search of the literature prior to June 2011 revealed thousands of studies regarding the relationship between GST genotypes and breast (Bailey et al, 1998), lung (Zheng et al, 2006), colon (Zhong et al, 1993), brain (Lai et al, 2005), bladder (Hung et al, 2004), prostate (Ntais et al, 2005) and other types of cancer (Gao et al, 2011) These studies have primarily focused on single nucleotide polymorphisms (SNPs) in GSTM1, GSTT1, and GSTP1
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