An Updated Pooled Analysis of Glutathione S-transferase Genotype Polymorphisms and Risk of Adult Gliomas

Abstract

Objective: 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. Methods: 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 χ 2 -based Q statistic and the I 2 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. Results: 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). Conclusions: 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.

Expression of CYP1A1 and GSTP1 in Human Brain Tumor Tissues in Pakistan

“…Among these enzymes, Glutathione-S-transferase (GST) is important for detoxifying exogenous and endogenous substances and protecting cells from the toxic effects of ROS (Narasimhan et al, 2011;Yao et al, 2012). The main function of these enzymes is to catalyze the formation of glutathione-S-conjugates with electrophiles, which is crucial for inactivation and subsequent excretion of these molecules (Koh et al, 2011;Nosheen et al, 2011).…”

“…Elevated expression of GSTs has been implicated in resistance to apoptosis initiated by a variety of stimuli (Francis et al, 1995). In addition, these enzymes are thought to play a role in detoxification and protecting DNA from oxidative damage (Yao et al, 2012). Other important enzyme involved in detoxification is the cytochrome P450 1A (CYP1A1) family of proteins which are involved in the bioactivation and detoxification of environmental toxins to the generation of chemical carcinogens (Shukla et al, 2013).…”

Comprehensive Study on Associations Between Nine SNPs and Glioma Risk

“…Recent genome-wide association studies (GWAS) have identified various new susceptibility regions (Wrensch et al, 2009;Rajaraman et al, 2012). Genes involved in the cell cycle and DNA repair, have been proposed to play role in glioma pathogenesis and progression, such as glutathione S-transferases(GSTs), excision repair cross-complementing rodent repair deficiency complementation group 1(ERCC1), X-ray repair cross-complementing groups 1(XRCC1) and X-ray repair cross-complementing groups 3 (XRCC3) (Wrensch et al, 2004;Custódio et al, 2011;Zhou et al, 2011;Yao et al, 2012).…”

Connotation of Glutathione-S-Transferase Enzyme Expression (GST) and Glutathione (GSH) in Human Head and Neck Squamous Cell Carcinoma Cancer

“…The elevated expression of GST has been implicated in resistance to apoptosis initiated by a variety of stimuli. In addition, GST thought to play an important function in detoxification and protecting DNA from oxidative damage [6]. In our present study we performed ELISA analysis for the determination of expression of specific activity of GSTs in HNSCC, which is involved in carcinogen detoxification.…”

“…Among them, Glutathione-S-transferase (GST) is significant for detoxifying exogenous and endogenous substances and protecting the cells from toxic effects of ROS [6,7]. The key role of GST is to catalyze the formation of glutathione-S-conjugates with electrophiles that is decisive for inactivation and consequent excretion of other molecules [8,9].…”