Abstract
BackgroundGlutathione S‐transferases (GSTs) polymorphisms may impact on chronic myeloid leukemia (CML) risk or heterogeneous responses to Imatinib mesylate (IM). The aim of this study was to evaluate the correlation between GSTs polymorphisms and CML risk, treatment response.MethodsWe genotyped GSTM1, GSTT1 null deletion polymorphisms, and GSTP1 Ile105Val polymorphism by PCR methods and BCR‐ABL transcripts were analyzed by qRT‐PCR in 104 CML patients and 104 sex‐ and age‐matched healthy individuals.ResultsIndividual analysis showed significant association of GSTM1 (p = 0.008; OR = 0.46; 95% CI: 0.26–0.82) and GSTP1 genes (p = 0.04; OR = 1.56; 95% CI: 1.016–2.423) with CML risk. The combined analysis indicated that GSTM1 null/GSTT1 present, GSTM1‐null/GSTP1M*(AG/GG) as well as GSTT1 present/ GSTP1M* genotype were associated with CML risk (ORg(‐):2.28; 95% CI: 1.29–4.04; ORgg: 2.85; 95% CI: 1.36–5.97; OR(‐)g: 1.75; 95% CI: 0.99–3.06, respectively). The proportion of CML cancer attributable to the interaction of smoking and GSTM1 null, GSTT1null, and GSTP1 M* was 42%, 39%, and 13%, respectively. Patients with GSTM1‐null and GSTP1 AG/GG genotype had significantly a lower rate of MMR achievement (p = 0.00; p = 0.009 respectively). Event‐free survival (EFS) percentage was similar between GSTM1 null and GSTM1 present patients (p = 0.21).ConclusionOur study suggests the influence of GSTM1 and GSTP1 polymorphisms on CML risk and treatment response. The interaction between GSTs polymorphisms and smoking plays a significant role on CML susceptibility.
Highlights
Chronic myeloid leukemia (CML) is a myeloproliferative disease and an outcome of the reciprocal translocation t (9;22) (q34;q11) or the BCR‐ABL1 fusion gene (Kassogue et al, 2014; Rostami, Hamid, Yaran, Khani, & Karimipoor, 2015)
A recent study has evaluated the effect of Glutathione S‐transferases (GSTs) polymorphisms on chronic myeloid leukemia (CML) susceptibility and treatment response, but the interaction between these genes and environmental exposures or risk factors such as cigarette smoke was not evaluated in CML development (Weich et al, 2016)
A number of studies have been carried out in different ethnic populations to evaluate the role of GSTs polymorphisms on CML susceptibility, but significance of association is still controversial
Summary
Chronic myeloid leukemia (CML) is a myeloproliferative disease and an outcome of the reciprocal translocation t (9;22) (q34;q11) or the BCR‐ABL1 fusion gene (Kassogue et al, 2014; Rostami, Hamid, Yaran, Khani, & Karimipoor, 2015). Earlier association studies have identified the roles of polymorphic variants in different crucial genes associated with predisposing individuals to CML, with incompatible results (Bruzzoni‐Giovanelli et al, 2015; He et al, 2014) These incompatibilities may be due to lifestyle factors, ethnic differences, environmental exposures in population cohorts studied (Davies et al, 2014; Özten, Sunguroğlu, & Bosland, 2012). A recent study has evaluated the effect of GST polymorphisms on CML susceptibility and treatment response, but the interaction between these genes and environmental exposures or risk factors such as cigarette smoke was not evaluated in CML development (Weich et al, 2016). Our overall aim of this work was to identify, for the first time, the correlation between GSTs genetic polymorphisms and CML cancer risk, treatment response and pattern its interactions with smoking as genetic modifiers in the etiology of CML disease in the Iranian population
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