GSTM1 and GSTP1, but not GSTT1 genetic polymorphisms are associated with chronic myeloid leukemia risk and treatment response. (October 2016)

• Record Type: Journal Article
• Authors: Weich, Natalia; Ferri, Cristian; Moiraghi, Beatriz; Bengió, Raquel; Giere, Isabel; Pavlovsky, Carolina; Larripa, Irene B.; Fundia, Ariela F.
• Is Part Of: Cancer epidemiology. Volume 44(2016:Oct.)
• Page Start: 16
• Page End: 21
• Publication Date: 2016-10
• Subjects: Glutathione-S-transferases -- Genetic polymorphisms -- Chronic myeloid leukemia risk -- Treatment outcome; Cancer -- Epidemiology -- Periodicals; Cancer -- Prevention -- Periodicals; Cancer -- Diagnosis -- Periodicals; Carcinogenesis -- Periodicals; 616.994005
• DOI: 10.1016/j.canep.2016.07.008
• Languages: English
• ISSNs: 1877-7821

Abstract

Highlights: GSTM1, GSTT1 and GSTP1 were studied in chronic myeloid leukemia patients and controls to assess their role on disease risk and treatment response. A trend toward significance was found for GSTP1 for a recessive model suggesting a potential association with the CML risk in Argentinean patients. Patients carrying combined GSTM1 -null/GSTP1-GG or GSTT1 -null/GSTP1-GG genotypes were associated with CML susceptibility. Patients with GSTM1 gene as well GSTP1 -GG genotype were associated to treatment failure This study highlights the identification of GST markers associated to CML susceptibility and treatment response. Abstract: Background: 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 (G S Ts) genetic polymorphisms in CML susceptibility and TKI clinical outcome. Materials: 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. Results: 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). Conclusions: This study highlights the significance of GSTM1 and GSTP1 polymorphisms on CML susceptibility and response to TKIs in the Argentinean population.