Glutathione S-transferase T1, M1 genetic polymorphisms in cases of acute leukemia

Abstract

7053 Background: Glutathione S-transferases (GSTs) are enzymes that detoxify potentially mutagenic and carcinogenic xenobiotics. The genes encoding isoenzymes M1 and T1 are polymorphic in humans and the phenotypic absence of enzyme activity is caused by a homozygous inherited deletion of the gene. The null genotype has been associated with incidence of several types of solid tumors. In addition, GSTM1 and GSTT1 polymorphisms have been considered as risk factors for developing acute leukemia in a number of studies; however the overall results of these previous reports are inconsistent and even controversial. Methods: The present study was undertaken to determine the frequencies of allelic variants in the GST genes in Egyptians and to explore the possibleinfluence of GSTT1, M1 genetic polymorphisms on the risk of acuteleukemia (myeloid and lymphoid). Results: The prevalence of the GSTM1 and GSTT1 homozygous deletions in 53 Egyptian patients with leukemia (21 ALL and 32 AML) and 87 racially,geographically, age and sex matched healthy control individuals was determined using a multiplex polymerase chain reaction (PCR)-based method. Thegenotype frequencies in the leukemia patients and normal controls were compared using Fisher's exact test. A significantly increased incidence of the GSTT1 null genotype was found in the group of patients compared to the controls (34% versus 15% P = 0.03, OR = 2.98, 95% CI 1.6–7.6). GSTM1 null genotype frequencies in cases were slightly but non-significantly higher than controls (68 % versus 49 %, respectively, P=0.07). Conclusions: In conclusion, this study has shown an increased risk of acute leukemia in adult Egyptian patients associated with the GSTT1 null genotype, as well as the combined GSTM1/T1 null genotype, particularly in AML cases. Study will be further extended to examine the relation between the GSTT1 and GSTM1 null genotypes and the patient's response to chemotherapy. No significant financial relationships to disclose.