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

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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.

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Acknowledgments

The authors thank Dr. Prof. Deborah Rund (Department of Hematology, Hebrew University—Hadassah Medical Center) and Dr.ssa Maria Teresa Voso (Istituto di Ematologia Università Cattolica S. Cuore) and others for providing us with additional data or information from their studies. The study was supported by grants from the Guangxi Science Fund for Distinguished Young Scholars (2012GXNSFFA060009), Guangxi Natural Science Foundation (2010GXNSFA013181, 2010GXNSFB013064), and National Natural Science Foundation of China (81160072, 81060234). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Hematology, The First Affiliated Hospital of Guangxi Medical University, Shuang Yong Rd. 6, Nanning, 530021, Guangxi Zhuang Autonomous Region, China

    Qiang Xiao, Donghong Deng, Hongying Li & Zhenfang Liu

  2. Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, China

    Qiang Xiao, Fanghui Ye, Lulu Huang, Bing Zhang, Bingbing Ye, Zengnan Mo & Xiaobo Yang

  3. Institute of Urology and Nephrology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China

    Zengnan Mo

  4. Department of Occupational Health and Environmental Health, School of Public Health, Guangxi Medical University, Nanning, Guangxi, China

    Xiaobo Yang

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Xiao, Q., Deng, D., Li, H. et al. GSTT1 and GSTM1 polymorphisms predict treatment outcome for acute myeloid leukemia: a systematic review and meta-analysis. Ann Hematol 93, 1381–1390 (2014). https://doi.org/10.1007/s00277-014-2050-z

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