Glutathione S-transferase genes variants and glioma risk: A case-control and meta-analysis study

Background: The glutathione S-transferase (GST) genes encode enzymes that metabolize carcinogenic compounds, and their variants, GSTP1 (Ile105Val and Ala114Val), GSTT1 (null/present), and GSTM1 (null/present), reduce enzyme activity that may affect the risk of developing cerebral glioma. This study undertook a case-control study and a meta-analysis to evaluate associations between these GST gene variants and the risk of glioma. Methods: The study enrolled 384 glioma patients (194 men and 190 women; mean age, 48.3 ± 9.2 years) and 340 healthy controls (174 men and 166 women; mean age, 46.5 ± 9.8 years). The amplification refractory mutation system assay was performed to identify GST gene variants of all 724 subjects. A meta-analysis enrolled 15 studies (including our case-control results) was performed. Results: Our case-control study found that the frequency of GSTP1 Ile105Val Val/Val genotype was significantly higher in the glioma group than that in the healthy controls (11.7% vs. 6.4%) (OR=1.50; 95% CI=1.05-2.04; P=0.01); the frequency of the Val/Ile + Ile/Ile genotypes was different from glioma patients and controls (88.3% vs. 93.6%) (OR=1.47(1.04-2.10); P=0.015); there were no associations between GSTP1 Ala114Val, GSTT1 (null/present) and GSTM1 (null/present) variants and glioma risk. Our meta-analysis confirmed that the GSTP1 Ile105Val variant was associated with an overall increased glioma risk. Moreover, our meta-analysis also confirmed the GSTP1 Ala114Val and GSTT1 null/present variants were associated with an increased glioma risk in the Caucasian population, rather than the Asian population. Conclusions: This study showed that GST gene variants were associated with an increased risk of glioma with ethnic differences. Future large-scale, multi center, controlled, prospective studies are required to support these findings and to determine how these GST gene variants may affect the pathogenesis of glioma.