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

Abstract

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.

Evaluation of total oxidative stress and antioxidant capacity of brain tumour patients attending referral hospitals in Addis Ababa, 2020: a comparative cross-sectional study

“…The current study shows that the serum GSSG of brain tumour patients was significantly increased and the counterbalancing GSH significantly decreased when compared to the control group. These findings agree with the reports of Liu et al [ 25 ], Gamcsik et al [ 26 ], Tadele et al [ 27 ] and Zhu et al [ 22 ]. Liu et al [ 23 ] reported that GSSG levels in primary brain tumours were more than twice the level found in healthy individuals.…”

“…The possible justification could be due to unusual high free radical production in brain tumours as reduced glutathione in healthy brain tissues normally is below 5% [ 22 , 28 ]. Mutations in glutathione (GST) enzymes, depletion of GST by overproduction of toxic substances and high activity of the glutathione-degrading enzyme could substantially reduce the protective activity and may increase the susceptibility of the brain to tumour development, suggesting that GST and GST genes are important molecules associated with the development and treatment of brain tumours [ 25 , 26 ].…”

lnc‑NLC1‑C inhibits migration, invasion and autophagy of glioma cells by targeting miR‑383 and regulating PRDX‑3 expression

“…Carcinogenic factors affecting glioma include high-risk congenital genetic and environmental factors. Previous studies have shown that glioma accounts for ~80% of all malignant tumors of the central nervous system (21,22). Glioma has a high incidence, a high recurrence rate and a poor prognosis (23,24).…”

Systematic analysis of potential targets of the curcumin analog pentagamavunon-1 (PGV-1) in overcoming resistance of glioblastoma cells to bevacizumab

“…A previous study showed that deletion in GSTM1 might be correlated with earlier age of onset of brain tumor ( Wiencke et al, 1997 ). Recently, a meta -analysis showed no association between GSTM1 (null/present) variants and glioma risk ( Liu et al, 2019 ).…”