Influence of glutathione S‐transferases (GSTM1, GSTT1, and GSTP1) genetic polymorphisms and smoking on susceptibility risk of chronic myeloid leukemia and treatment response

Abstract

Background Glutathione 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. Methods We 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. Results Individual 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). Conclusion Our 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.

Genetic Polymorphism of GSTP1, GSTM1 and GSTT1 Genes and Susceptibility to Chronic Myeloid Leukaemia

“…Such cancers include lung cancer (Mir Muhammad NasirUddin, 2014), ovarian cancer (Coughlin and Hall, 2002) and breast cancer (Hashemi et al, 2012). Previous studies have reported about GSTs association with heamatological malignancy, but with conflicting findings as mentioned previously (Dunna et al, 2012;Zhou et al, 2013;Rostami internal positive control.…”

“…Some genes of cytosolic enzymes play a crucial role in the detoxification of activated carcinogens and implications in cancer progress, particularly GSTP1, GSTM1, and GST1 (Sailaja et al, 2010). Polymorphisms in these genes lead to the absence or decreased detoxification ability of enzymes, their dysfunction, and finally may impact on the risk of cancer development and heterogeneous drug responsiveness Editorial Process: Submission:10/06/2019 Acceptance:01/10/2020 (Rostami et al, 2019).…”

“…Individuals who are homozygous for this allele are unable to produce the GSTM1 protein. The null variant of GSTΜ1 is of particular interest as a plethora of studies have demonstrated the difference in its susceptibility, exposure to environmental toxicants, and resistance to chemotherapy treatment (Rostami et al, 2019;Mondal et al, 2005;Bhat et al, 2012). The frequency of the GSTM1 null genotype ranges from 23% to 48% in African populations, 33% to 63% in Asian populations, 39% to 62% in European populations, and 23% to 62% in U.S. populations (Coughlin and Hall, 2002).…”

“…The latter is a non-functional allele arising from the deletion of the GSTT1 gene, with null GSTT1 (0/0) phenotype individuals being unable to form the GSTT1 protein (Bajpai et al, 2007). The homozygous GSTT1 null phenotype has been described in different populations and shows wide variation (Bajpai et al, 2007;Rostami et al, 2019;Lordelo et al, 2012). The frequency of the GSTT1 null genotype has been described in different ethnic groups with varying degrees as follows: 22% to 29% in African-Americans, 16% to 64% in Asian individuals, 15% to 27% in whites, 10% to 21% in European populations and 10% to 12% in Mexican-Americans (Coughlin and Hall, 2002).…”

<p>Association Between Glutathione S-Transferase (GST) Polymorphisms and Schizophrenia in a Chinese Han Population</p>

“…24 Among GST genes, GSTM1, GSTT1, and GSTP1 have well-defined single nucleotide polymorphisms (SNPs). 25 The GSTT1 gene contains two alleles, the functional gene GSTT1+ and the nonfunctional gene GSTT1null. Similarly, the GSTM1 gene contains the functional gene GSTM1+ and the nonfunctional gene GSTM1null.…”