GSTT1 and GSTM1 polymorphisms predict treatment outcome for acute myeloid leukemia: a systematic review and meta-analysis

Ann Hematol. 2014 Aug;93(8):1381-90. doi: 10.1007/s00277-014-2050-z. Epub 2014 Mar 29.

Abstract

Glutathione S-transferases (GSTs) contribute to the metabolism of different xenobiotics and anticancer drugs and confer protection against oxidative stress thus may influence the treatment outcome of acute myeloid leukemia (AML). Studies regarding the association between GSTT1 and GSTM1 polymorphisms and treatment outcome in AML patients showed an inconsistent result. A systematic review and meta-analysis were performed to further explore this association. PubMed, Hartford User Group Exchange (HUGE), and China National Knowledge Infrastructure (CNKI) databases were searched for all related publications. Statistical analyses were analyzed by using RevMan 5.0 and Stata 9.0 softwares. A total of 1,837 patients in 11 studies were included. GSTT1 null genotype was found to be significantly associated with a reduced response after first course of induction chemotherapy (odds ratio (OR) = 0.894, 95 % confidence interval (CI) = 0.818-0.977, P = 0.013), progression-free survival (PFS; hazard ratio (HR) = 0.698, 95 % CI = 0.520-0.937, P = 0.017), and overall survival (OS; HR = 0.756, 95 % CI = 0.618-0.925, P = 0.007) in Asian population. GSTM1/GSTT1 double-null genotype was also identified to be significantly associated with response after the first course of induction chemotherapy (OR = 0.40, 95 % CI = 0.24-0.67, P = 0.0003). Our study suggested that GSTT1 null genotype and GSTT1/GSTM1 double-null genotype were associated with a worse treatment outcome for AML patients, especially in Asian population.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Anthracyclines / administration & dosage
  • Anthracyclines / pharmacokinetics
  • Antineoplastic Combined Chemotherapy Protocols / pharmacokinetics
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • China / epidemiology
  • Cytarabine / administration & dosage
  • Cytarabine / pharmacokinetics
  • Disease-Free Survival
  • Female
  • Gene Deletion
  • Genotype
  • Glutathione Transferase / analysis
  • Glutathione Transferase / genetics*
  • Glutathione Transferase / physiology
  • Humans
  • Inactivation, Metabolic
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / mortality
  • Male
  • Middle Aged
  • Mutation
  • Neoplasm Proteins / analysis
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / physiology
  • Odds Ratio
  • Pharmacogenetics
  • Remission Induction
  • Survival Analysis
  • Treatment Outcome
  • Young Adult

Substances

  • Anthracyclines
  • Neoplasm Proteins
  • Cytarabine
  • glutathione S-transferase T1
  • Glutathione Transferase
  • glutathione S-transferase M1