Glutathione S-Transferase M1 and T1 Genes and Susceptibility to Chronic Myeloid Leukemia: A Meta-Analysis

Abstract

Variants of glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) genes have been implicated as risk factors for chronic myeloid leukemia (CML). However, the genetic association studies that examined the relation between the null genotypes of GSTM1 and GSTT1 genes and risk of developing CML gave conflicting or inconclusive results. In an attempt to interpret these results, a meta-analysis of all available studies (nine studies, with 757 cases and 1959 controls) was performed. In the meta-analysis the pooled odds ratios (OR) were estimated using random effects models. The heterogeneity between studies, the sources of potential bias, and the consistency of genetic effects across ethnicities were explored. Cumulative meta-analysis was also performed. Overall, the meta-analysis showed nonsignificant association between GSTM1 null genotype and CML (OR = 1.00 [0.83-1.20]) and lack of heterogeneity between the studies (p(Q) = 0.87). The association was also nonsignificant in Whites, East Asians, and Indians: OR = 1.38 (0.43-4.46), 0.94 (0.65-1.35), and 1.16 (0.74-1.82), respectively. However, GSTT1 null genotype was associated with increased risk of CML (OR = 1.57 [1.13-2.17]) and the heterogeneity between studies was significant (p(Q) = 0.04). In Indians, the association was significant (OR = 2.89 [1.56-5.35]) whereas in East Asians it was not significant (OR = 1.07 [0.74-1.54]). The combined GSTM1 normal/GSTT1 null genotypes produced significant association (OR = 1.95 [1.17-3.24]). Cumulative meta-analysis for GSTT1 gene showed an upward trend in risk effect, whereas the trend was downward in GSTM1. There was a differential magnitude of effect in large versus small studies. In conclusion, the accumulated evidence indicated an association between GSTT1 null genotype and CML.