Glutathione S Transferase T1 and M1 Gene Polymorphisms and Risk of Myeloid Leukemias

Leukaemias in general population result from complex interaction between multiple genetic and environmental factors over time. The interplay of xenobiotic exposure, endogenous physiology, and genetic variability of multiple loci may facilitate knowledge about leukaemia aetiology and the identification of individuals who are at increased risk of developing leukaemias. Xenobiotics are chemical substances that are foreign to the biological system, adverse effects of xenobiotics are exerted via covalent interactions between intermediate metabolites and genetic materials or proteins and their related metabolites. In order to avoid accumulation of lipophilic xenobiotics in cells and tissues, enzymatic reactions of xenobiotic metabolism that can be divided into two distinct phases are needed. Phase II enzymes known as Glutathione S Transferases (GST) catalyze the conjugation of glutathione or glucuronide with reactive electrophiles and thus detoxify procarcinogens and carcinogens. Human GSTs: GSTM1 and GSTT 1 are two genes whose products can modify endogenous and exogenous toxic substrates to less reactive species through a number of mechanisms that play a critical role in the system which protects against reactive oxygen species, the breakdown of peroxidized lipid and oxidized DNA. In the present study we attempted to study null genotype frequency of GSTT 1 and GSTM1 genes in myeloid leukaemias by multiplex PCR. Our study included 50 newly diagnosed patients of myeloid leukemias: 25 cases with Acute Myeloid Leukemia (AML), 25 with Chronic Myeloid Leukemia (CML), and 30 healthy volunteers. A statistical significant difference was found with GSTT1 null genotypes frequency in AML patients as compared to controls 13/25 (52%) versus 4/30 (13.3%): OR=7.04 (1.926.1). There was no statistical significant difference in the frequencies of the GSTM1 null genotypes between AML patients and control (p-value 0.084). There was a significant association between patients achieving complete remission and GSTT1 genotype i.e. those with GSTT1 gene present were more liable to complete remission (p-value 0.008), with no statistical significant association between follow-up cases and GSTM1 genotype (p-value 0.290). There was a statistical significant difference in GSTT1 null genotypes frequency in CML patients as compared to controls 10/25 (40%) versus 4/30 (13.3%): Odds ratio {OR=4.3 (1.15-16.2)}. On the other hand there was no significant difference in frequency Corresponding author: Dr. Laila A. Hegazy, Clinical and Chemical Pathology, Faculty of Medicine, Cairo University. of the GSTM1 null genotypes between CML patients and control (p-value 0.80). In conclusion our results revealed a strong association between GSTT1 null genotypes and risk of AML and CML, with a valuable influence on the fate of AML patients where patients with GSTT1 present alleles are more liable to achieve complete remission than those with deletions of the gene. There was no association encountered between GSTM1 null genotype and risk of AML or CML.