title: GSTT1 and GSTM1 polymorphisms and myelodysplastic syndrome risk: a systematic review and meta-analysis.
abstract: 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 I(2) 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; I(2) = 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; I(2) = 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.
authors.affiliation: Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Tufts University School of Medicine, Boston, MA, USA.
authors.forename: Issa J
authors.initials: IJ
authors.lastname: Dahabreh
authors.forename: Stavroula
authors.initials: S
authors.lastname: Giannouli
authors.forename: Vaia
authors.initials: V
authors.lastname: Gota
authors.forename: Michael
authors.initials: M
authors.lastname: Voulgarelis
mesh_terms: D016022:Case-Control Studies; D005500:Follow-Up Studies; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D009190:Myelodysplastic Syndromes / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D009367:Neoplasm Staging; D016017:Odds Ratio; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D012307:Risk Factors; D015996:Survival Rate
chemical_list: D005982:Glutathione Transferase; C413545:glutathione S-transferase T1