Polymorphic Variation in Glutathione-S-transferase Genes and Risk of Chronic Myeloid Leukaemia in the Kashmiri Population

Abstract

Cancer is a complex disease and the genetic susceptibility to it could be an outcome of the inherited differencein the capacity of xenobiotic metabolizing enzymes. Glutathione-S-transferases (GSTs) are phase II metabolizingenzymes whose various genotypes have been associated with increased risk of different types of cancer. Nullmutations caused by the deletion of the entire gene result in the absence of the enzymatic activity and increasein the risk of developing cancer including chronic myeloid leukaemia (CML). In the present case-control studywe evaluated the effect of null mutations in GSTM1 and GSTT1 genes on the risk of developing CML. Thestudy included 75 CML patients (43 males and 32 females; age (mean ± S.D) 42.3 ± 13.4 years) and unrelatednon-malignant controls (76 male and 48 females; age (mean ± S.D) 41.5 ± 12.9). The distribution of GSTM1 andGSTT1 genotypes in CML patients and controls was assessed by multiplex-PCR method. Logistic regressionwas used to assess the relationship between GSTM1 and GSTT1 genotypes and risk of CML. Chi-square testwas used to evaluate the trend in modulating the risk to CML by one or more potential high risk genotype.Although GSTM1 null genotype frequency was higher in CML patients (41%) than in the controls (35%), it didnot reached a statistical significance (OD = 1.32, 95% CI: 0.73–2.40; P value = 0.4295). The frequency of GSTT1null genotypes was higher in the CML patients (36%) than in the controls (21%) and the difference was foundto be statistically significant (OD = 2.12, 95% CI: 1.12–4.02; P value = 0.0308). This suggests that the presenceof GSTT1genotype may have protective role against the CML. We found a statistically significant (OD = 3.09,95% CI: 1.122–8.528; P value = 0.0472) interaction between the GSTM1 and GSTT1 null genotypes and thusindividuals carrying null genotypes of both GSTM1 and GSTT1 genes are at elevated risk of CML.