Abstract
Glutathione S-transferase (GST), a phase II metabolizing enzyme, plays an important role in the cellar defense system, and its activity may modulate leukemia risk. A large body of evidence has shown the possible relevance of functional polymorphisms of the genes that encode GSTs μ, π, and θ (GSTM1, GSTP1, and GST1, respectively) to the genetic susceptibility of chronic myeloid leukemia (CML). Because of the lack of available conclusive data, we performed a meta-analysis of all relevant available studies to derive a more precise estimation of the relationship. A comprehensive literature search of PubMed and Web of Knowledge electronic databases was conducted to collect relevant studies until December 20, 2013, and the extracted data were statistically analyzed using Review Manager version 5.2. Finally, 16 eligible studies were identified in the literature. The GSTT1 null genotype was associated with an increased risk of CML, as were the double null GSTT1 and GSTM1 genotypes. These findings suggest that heritable GST status influences the risk of developing CML and that more attention should be paid to carriers of these susceptibility genes.
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References
Karkucak M et al. Investigation of GSTP1 (Ile105Val) gene polymorphism in chronic myeloid leukaemia patients. Int J Hum Genet. 2012;12(3):145–9.
Nowicki MO et al. BCR/ABL oncogenic kinase promotes unfaithful repair of the reactive oxygen species-dependent DNA double-strand breaks. Blood. 2004;104(12):3746–53.
Ishikawa K, Ishii H, Saito T. DNA damage-dependent cell cycle checkpoints and genomic stability. DNA Cell Biol. 2006;25(7):406–11.
Kennedy RD, D’Andrea AD. DNA repair pathways in clinical practice: lessons from pediatric cancer susceptibility syndromes. J Clin Oncol. 2006;24(23):3799–808.
Voso MT et al. Increased risk of acute myeloid leukaemia due to polymorphisms in detoxification and DNA repair enzymes. Ann Oncol. 2007;18(9):1523–8.
Taspinar M et al. CYP1A1, GST gene polymorphisms and risk of chronic myeloid leukemia. Swiss Med Wkly. 2008;138(1–2):12–7.
Bhatla D et al. DNA repair polymorphisms and outcome of chemotherapy for acute myelogenous leukemia: a report from the Children’s Oncology Group. Leukemia. 2008;22(2):265–72.
Hayes JD, Pulford DJ. The glutathione S-transferase supergene family: regulation of GST and the contribution of the isoenzymes to cancer chemoprotection and drug resistance. Crit Rev Biochem Mol Biol. 1995;30(6):445–600.
Mannervik B et al. Nomenclature for mammalian soluble glutathione transferases. Methods Enzymol. 2005;401:1–8.
Alves S et al. The GSTM1 and GSTT1 genetic polymorphisms and susceptibility to acute lymphoblastic leukemia in children from north Portugal. Leukemia. 2002;16(8):1565–7.
Strange RC et al. Glutathione-S-transferase family of enzymes. Mutat Res. 2001;482(1–2):21–6.
Sailaja K et al. Association of the GSTP1 gene (Ile105Val) polymorphism with chronic myeloid leukemia. Asian Pac J Cancer Prev. 2010;11(2):461–4.
Dunna NR et al. Association of GSTP1 gene (I105V) polymorphism with acute leukaemia. J Genet. 2012;91(1):e60–3.
Watson MA et al. Human glutathione S-transferase P1 polymorphisms: relationship to lung tissue enzyme activity and population frequency distribution. Carcinogenesis. 1998;19(2):275–80.
Harries LW et al. Identification of genetic polymorphisms at the glutathione S-transferase Pi locus and association with susceptibility to bladder, testicular and prostate cancer. Carcinogenesis. 1997;18(4):641–4.
Bajpai P, Tripathi AK, Agrawal D. Increased frequencies of glutathione-S-transferase (GSTM1 and GSTT1) null genotypes in Indian patients with chronic myeloid leukemia. Leuk Res. 2007;31(10):1359–63.
Bhat G et al. Polymorphic variation in glutathione-S-transferase genes and risk of chronic myeloid leukaemia in the Kashmiri population. Asian Pac J Cancer Prev. 2012;13(1):69–73.
Chen HC et al. Genetic polymorphisms of metabolic enzymes CYP1A1, CYP2D6, GSTM1 and GSTT1 and leukemia susceptibility. Eur J Cancer Prev. 2008;17(3):251–8.
Hishida A et al. GSTT1 and GSTM1 deletions, NQO1 C609T polymorphism and risk of chronic myelogenous leukemia in Japanese. Asian Pac J Cancer Prev. 2005;6(3):251–5.
Loffler H et al. Reduced risk for chronic myelogenous leukemia in individuals with the cytochrome P-450 gene polymorphism CYP1A1*2A. Blood. 2001;98(13):3874–5.
Lordelo GS et al. Association between methylene tetrahydrofolate reductase and glutathione S-transferase M1 gene polymorphisms and chronic myeloid leukemia in a Brazilian population. Genet Mol Res. 2012;11(2):1013–26.
Lourenco GJ et al. Polymorphisms of glutathione S-transferase mu1 (GSTM1) and theta 1 (GSTT1) genes in chronic myeloid leukaemia. Eur J Haematol. 2005;75(6):530–1.
Mondal BC et al. Glutathione S-transferase M1 and T1 null genotype frequency in chronic myeloid leukaemia. Eur J Cancer Prev. 2005;14(3):281–4.
Ovsepian VA, Vinogradova E, Sherstneva ES. Cytochrome P4501A1, glutathione S-transferase M1 and T1 gene polymorphisms in chronic myeloid leukemia. Genetika. 2010;46(10):1360–2.
Ozten N, Sunguroglu A, Bosland MC. Variations in glutathione-S-transferase genes influence risk of chronic myeloid leukemia. Hematol Oncol. 2012;30(3):150–5.
Souza CL et al. Polymorphisms in the glutathione S-transferase theta and mu genes and susceptibility to myeloid leukemia in Brazilian patients. Genet Mol Biol. 2008;31(1):39–41.
Lemos MC et al. Genetic polymorphism of CYP2D6, GSTM1 and NAT2 and susceptibility to haematological neoplasias. Carcinogenesis. 1999;20(7):1225–9.
Ouerhani S et al. Influence of genetic polymorphisms of xenobiotic metabolizing enzymes on the risk of developing leukemia in a Tunisian population. Bull Cancer. 2011;98(12):95–106.
Lopez-Lopez, E., et al., A systematic review and meta-analysis of MTHFR polymorphisms in methotrexate toxicity prediction in pediatric acute lymphoblastic leukemia. Pharmacogenomics J, 2012.
Gurion R et al. Has the time for first-line treatment with second generation tyrosine kinase inhibitors in patients with chronic myelogenous leukemia already come? Systematic review and meta-analysis. Haematologica. 2013;98(1):95–102.
Egger M et al. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315(7109):629–34.
Kawajiri K et al. The CYP1A1 gene and cancer susceptibility. Crit Rev Oncol Hematol. 1993;14(1):77–87.
Tan W et al. Impact of genetic polymorphisms in cytochrome P450 2E1 and glutathione S-transferases M1, T1, and P1 on susceptibility to esophageal cancer among high-risk individuals in China. Cancer Epidemiol Biomarkers Prev. 2000;9(6):551–6.
Zintzaras E. Glutathione S-transferase M1 and T1 genes and susceptibility to chronic myeloid leukemia: a meta-analysis. Genet Test Mol Biomarkers. 2009;13(6):791–7.
Das P, Shaik AP, Bammidi VK. Meta-analysis study of glutathione-S-transferases (GSTM1, GSTP1, and GSTT1) gene polymorphisms and risk of acute myeloid leukemia. Leuk Lymphoma. 2009;50(8):1345–51.
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This work was supported by the National Natural Science Foundation of China (No. 81071765; 81372379) and the Fundamental Research Funds for the Central Universities (No. 08143047) of China.
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H.-r. He and X.-x. Zhang contributed equally to this manuscript
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He, Hr., Zhang, Xx., Sun, Jy. et al. Glutathione S-transferase gene polymorphisms and susceptibility to chronic myeloid leukemia. Tumor Biol. 35, 6119–6125 (2014). https://doi.org/10.1007/s13277-014-1810-7
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DOI: https://doi.org/10.1007/s13277-014-1810-7