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

Authors

  • Issa J. Dahabreh,

    1. Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Tufts University School of Medicine, Boston, MA, USA
    Search for more papers by this author
  • Stavroula Giannouli,

    1. Department of Hematology, Medical School, National University of Athens, Athens, Greece
    Search for more papers by this author
  • Vaia Gota,

    1. Haematology Research Laboratory, Biomedical Research Foundation, Academy of Athens, Athens, Greece
    Search for more papers by this author
  • Michael Voulgarelis

    Corresponding author
    1. Department of Pathophysiology, Medical School, National University of Athens, Athens, Greece
    • Department of Pathophysiology, Medical School, National University of Athens, 75 Mikras Asias St., 11527 Athens, Greece
    Search for more papers by this author
    • Tel: +30 210 7462648, Fax: +30 210 7462664


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 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 (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 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.

Ancillary