J Cancer 2019; 10(19):4679-4688. doi:10.7150/jca.29398 This issue
1. Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, People's Republic of China
2. Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410008, People's Republic of China
3. Department of Pharmacy, the Second Xiangya Hospital, Central South University; Institute of Clinical Pharmacy, Central South University, Changsha 410011, People's Republic of China.
4. Department of Pharmacy, Xiangya Hospital, Central South University, Changsha 410078, People's Republic of China
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.
Keywords: glutathione S-transferase genes, glioma, gene polymorphism, risk, meta-analysis