title: GSTM1 and GSTP1, but not GSTT1 genetic polymorphisms are associated with chronic myeloid leukemia risk and treatment response.
abstract: Chronic myeloid leukemia (CML) is associated to the BCR-ABL1 oncogene and can successfully be treated with tyrosine kinase inhibitors (TKIs). However, it remains still under investigation which molecular factors may influence CML risk or varying responses to TKIs. The aim of this study was to assess the role of Glutathione-S-transferases (GSTs) genetic polymorphisms in CML susceptibility and TKI clinical outcome.
  
  
  
  Deletion polymorphisms in GSTM1 and GSTT1 genes and the single nucleotide polymorphism in GSTP1 c.319A>G (rs1695; p.105Ile>Val) were genotyped by PCR methods in 141 CML treated patients and 141 sex- and age-matched healthy individuals.
  
  
  
  Individual analysis of each GST gene showed no association with CML risk. A trend toward significance (p=0.07) for a recessive model was found for GSTP1 (OR: 2.04; CI: 0.94-4.4). However, the combined analysis showed that GSTM1-null/GSTP1-GG as well as GSTT1-null/GSTP1-GG were associated with CML development (p=0.03; OR: 3.54 CI: 1.2-14.57; p=0.05; OR: 12.65; CI: 1.17-21.5). The relationship with treatment outcome showed that the presence of GSTM1 gene was significantly linked with an inferior rate of major molecular response (p=0.048) and poor event free-survival (EFS) (p=0.02). Furthermore, a group of patients with GSTP1-GG genotype were significantly associated with reduced EFS comparing to those carrying other GSTP1 genotypes (p=0.049). GSTP1-GG genotypes had short time to treatment failure in a group of patients unresponsive to TKIs comparing to other GSTP1 genotypes (p=0.03).
  
  
  
  This study highlights the significance of GSTM1 and GSTP1 polymorphisms on CML susceptibility and response to TKIs in the Argentinean population.
authors.affiliation: Laboratorio de Genética Hematológica, IMEX, CONICET-Academia Nacional de Medicina, Buenos Aires, Argentina.
authors.forename: Natalia
authors.initials: N
authors.lastname: Weich
authors.affiliation: Laboratorio de Genética Hematológica, IMEX, CONICET-Academia Nacional de Medicina, Buenos Aires, Argentina.
authors.forename: Cristian
authors.initials: C
authors.lastname: Ferri
authors.affiliation: Servicio de Hematología, Hospital Ramos Mejía, Buenos Aires, Argentina.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Moiraghi
authors.affiliation: Departamento de Hemato-oncología, Academia Nacional de Medicina, Buenos Aires, Argentina.
authors.forename: Raquel
authors.initials: R
authors.lastname: Bengió
authors.affiliation: FUNDALEU, Buenos Aires, Argentina.
authors.forename: Isabel
authors.initials: I
authors.lastname: Giere
authors.affiliation: FUNDALEU, Buenos Aires, Argentina.
authors.forename: Carolina
authors.initials: C
authors.lastname: Pavlovsky
authors.affiliation: Laboratorio de Genética Hematológica, IMEX, CONICET-Academia Nacional de Medicina, Buenos Aires, Argentina.
authors.forename: Irene B
authors.initials: IB
authors.lastname: Larripa
authors.affiliation: Laboratorio de Genética Hematológica, IMEX, CONICET-Academia Nacional de Medicina, Buenos Aires, Argentina. Electronic address: affundia@hematologia.anm.edu.ar.
authors.forename: Ariela F
authors.initials: AF
authors.lastname: Fundia
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012307:Risk Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; C413545:glutathione S-transferase T1
keywords: Chronic myeloid leukemia risk; Genetic polymorphisms; Glutathione-S-transferases; Treatment outcome