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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 ofGSTM1andGSTT1null polymorphisms on MDS risk. We searched the PubMed and SCOPUS databases to identify peer-reviewed published case-control studies investigating the association betweenGSTT1and/orGSTM1null 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 theGSTT1meta-analysis (1471 cases, 1907 controls) and 10 were considered eligible for theGSTM1meta-analysis (1161 cases, 1668 controls). For theGSTT1polymorphism, there was moderate between study heterogeneity (pQ = 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 theGSTM1polymorphisms 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). TheGSTT1null genotype is a significant risk factor for MDS development. Gene-environment interactions need to be further explored.