Polymorphism of genes encoding glutathione S-transferases GSTM1, GSTT1 GSTP1 is one of the genetic predictors of susceptibility to cancers in the adults. The frequency of deletions of GSTM1. GSTT1 genes and transition A-G in GSTP1 gene were taken into consideration. THE AIM of this study was to investigate the role of GST genes polymorphisms as a genetic risk factor for acute lymphoblastic leukaemia (ALL), and to study the relationship of these polymorphisms with clinical outcome in childhood leukaemias.
Material and methods: 86 children with newly diagnosed acute leukaemia (female: male ratio = 37:49. median age = 7.8 years) and 460 healthy controls were examined using the PCR and PCR-RFLP methods to identify polymorphisms within GSTM1, GSTT1 and GSTP1 genes. In the group of children with ALL. the frequency of relapses, deaths, clinical course, immunophenotype of blasts and the initial response to prednisone were also analyzed.
Results: the higher frequency of A-G transition in the GSTP1 gene was identified in the group of children with ALL in comparison to healthy controls (OR=3.13, 95%CI=1.4-7). We also found that the combination of GSTPl (Val/Val) and GSTM1 null genotypes further increased the risk of ALL (OR= 10.63, 95%CI=3.47 - 32.58; p =0.0001). No differences in the frequency of GSTM1 and GSTTI genes between both groups (OR=1; 95%CI=0,59-1,74 and OR=0, 71; 95%CI=0.45-1.13 respectively) were observed. Statistical analysis has not revealed any connections between polymorphisms within glutathione S-transferases genes and the frequency of relapses and death or poor initial response to prednisone. However, the biphenotypic immunophenotype or B-line blasts were the risk factors of relapse or death of progression in ALL (p=0.03).
Conclusion: transition in exon 5 of GSTP1 gene (alone or combined with GSTM1 deletion) may be one of the molecular predictors of higher susceptibility to acute leukaemia in children. but not of the clinical course of this disease.