Thesis (Ph.D.) - Cairo University - Faculty of Medicine - Department of Clinical and Chemical Pathology

Purpose The aim of our study was to investigate the role of genetic polymorphisms in Glutathione S-transferase Omega (GSTO1 and GSTO2) genes in childhood acute lymphoblastic leukemia susceptibility, and their impact on prognosis of childhood ALL patients . Methods The polymorphism of GSTO1 and GSTO2 genes were analyzed in 96 ALL patients compared with 96 healthy Egyptian children by PCR-based restriction fragment length polymorphism (RFLP) analysis. Results Genotyping of the GSTO1gene revealed no statistically significant difference in genotypes distribution between patients and control groups (p=0.106). However, when ALL cases were divided into de novo and remission groups,it was found that the frequency of homozygous and heterozygous GSTO1 mutations was significantly higher in the de novo group compared to the control group[63.0%vs 43.4% respectively, p=0.028, OR(95%CI):2.222(1.083-4.558)]. As regards The GSTO2 gene, our study demonstrated a statistically significant difference in genotypes distribution between patients and control groups; the frequency of the homozygous GSTO2 mutation was significantly higher in the de novo group compared to healthy subjects (17.3%vs 2.0%, p= 0.002 ).In addition ,the frequency of the homozygous and heterozygous GSTO2 mutation was significantly higher in the remission group compared to the control group [(82.0%vs 63.6%, p=0.012, OR(95% CI)=2.929(1.238- 6.929)]. No association was found between the presence of GSTO1 or GSTO2 mutation or their combined presence and the available bad prognostic factors (age>10 years, T-ALL phenotype, WBCs more than 50.000x10⁹/L) Conclusion We concluded that polymorphisms in the GSTO1 and O2 genes allele are present in an increased percentage of Childhood acute lymphoblastic leukemia patients. Thus it might play an important role as a genetic risk factor in development of ALL in Egyptian children

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