title: GSTT1 and GSTM1 polymorphisms predict treatment outcome for acute myeloid leukemia: a systematic review and meta-analysis.
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.
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Guangxi Medical University, Shuang Yong Rd. 6, Nanning, 530021, Guangxi Zhuang Autonomous Region, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xiao
authors.forename: Donghong
authors.initials: D
authors.lastname: Deng
authors.forename: Hongying
authors.initials: H
authors.lastname: Li
authors.forename: Fanghui
authors.initials: F
authors.lastname: Ye
authors.forename: Lulu
authors.initials: L
authors.lastname: Huang
authors.forename: Bing
authors.initials: B
authors.lastname: Zhang
authors.forename: Bingbing
authors.initials: B
authors.lastname: Ye
authors.forename: Zengnan
authors.initials: Z
authors.lastname: Mo
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Yang
authors.forename: Zhenfang
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000008:administration & dosage / Q000493:pharmacokinetics; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics / Q000627:therapeutic use; D002681:China / Q000453:epidemiology; D003561:Cytarabine / Q000008:administration & dosage / Q000493:pharmacokinetics; D018572:Disease-Free Survival; D005260:Female; D017353:Gene Deletion; D005838:Genotype; D005982:Glutathione Transferase / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D006801:Humans; D008658:Inactivation, Metabolic; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009363:Neoplasm Proteins / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D016017:Odds Ratio; D010597:Pharmacogenetics; D012074:Remission Induction; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018943:Anthracyclines; D003561:Cytarabine; D005982:Glutathione Transferase; D009363:Neoplasm Proteins; C413545:glutathione S-transferase T1