GSTT1 and GSTM1 polymorphisms and myelodysplastic syndrome risk: a systematic review and meta‐analysis

Glutathione‐S‐transferace polymorphisms may make hematopoietic lineage cells susceptible to genotoxicity following exposure to heavy metals or benzene. We conducted a systematic review and meta‐analysis to define the effect of GSTM1 and GSTT1 null polymorphisms on MDS risk. We searched the PubMed and SCOPUS databases to identify peer‐reviewed published case‐control studies investigating the association between GSTT1 and/or GSTM1 null genotypes and development of MDS. Between‐study heterogeneity was assessed using Cochran's Q statistic and the I² statistic. Odds ratios from individual studies were pooled using fixed and random effects models. Thirteen studies were considered eligible for the GSTT1 meta‐analysis (1471 cases, 1907 controls) and 10 were considered eligible for the GSTM1 meta‐analysis (1161 cases, 1668 controls). For the GSTT1 polymorphism, there was moderate between study heterogeneity (p_Q = 0.01; I² = 52.3%) and the null genotype was significantly associated with increased risk of MDS development, random effects OR = 1.43 (95% CI, 1.09–1.89); p = 0.01. For the GSTM1 polymorphisms there was moderate between‐study heterogeneity (p = 0.07; I² = 43.1%) and the random effects OR = 1.02 (95% CI, 0.82–1.28) was non‐significant (p = 0.85). The GSTT1 null genotype is a significant risk factor for MDS development. Gene‐environment interactions need to be further explored.