Relationship Between Genetic Polymorphisms And Acute Myeloid Leukemia And Recurrent Chromosome Translocations

Object To investigate the impact of RAD51, XRCC3, GSTM1, GSTT1 and NQO1 genotypes on the acute myelois leukemia(AML) susceptibility and recurrent chromosome chromosome tranlocations of AML.Methods RAD51,XRCC3, NQO1, GSTT1 and GSTM1 genotypes were detected in 306 adult patients with de novo AML and 458 controls by PCR or PCR-RFLP.Results There was a significant difference of the incidence of RAD51G135C G/C genotype between AML patients and controls. In individuals with the XRCC3Thr24tMet polymorphic allele, the odds ratios for inv(16) and/or t(16;16)/CBFB- MYH11(＋) AML risk were elevated to 6.133 (95%CI: 2.227-16.887, P=0.000) , The risk of the development of inv(16) and/or t(16;16)/CBFB-MYH11(＋) AML was found to be significantly increased when both variant RAD51-135C and XRCC3-241Met alleles are present (OR=8.697, 95%CI: 2.384-31.370, P=0.000) , If we further combine a null GSTM1 genotype or NQO1C609T polymorphic allele with the double HR gene variants, the risk of inv(16) and/or t(16; 16)/CBFB-MYH11 (＋) AML was further increased to 12.656(95%CI: 2.411-66.441, P=0.000) and 17.091 (95%CI: 2.801-104.291, P=0.000), respectively.There was a significant difference of the incidence of GSTM1 null genotype between AML patients and controls but was no difference of the incidence of. GSTT1 null genotype. The frequency of cases with NQO1C609T C/T and variant genotype was significantly higher among total AML case (odds ratio [OR] was 2.480 and 1.477, respectively) subjects compared with controls, especially among AML with t(8;21)(q22;q22)/AML-ETO fusion gene(OR was 2.789; 95% confidence interval [CI] was 1.055-3.375) and patient with t(15;17)(q22;q 11)/PML-RARct fusion gene(OR was 2.911 and 1.734, respectively; 95%CI was 1.524-5.559 andl.046-2.874, respectively). Conclusion The frequency of cases with NQO1C609T C/T and T/T genotype was significantly higher among adult primary AML case, especially among AML patients with t(8;21)(q22;q22)/AML-ETO fusion gene and patients with t(15;17)(q22;q 11)/PML-RARa fusion gene. There was a significant difference of the incidence of GSTM1 null genotype between AML patients and controls. XRCC3 Thr241Met genotype was significantly higher among AML patients with inv(16) or t(16;16)/CBFB-MYH11 fusion gene, XRCC3 Thr241Met combined with RAD51G135C G/C or C/C and GSTM1 null or NQO1C609T C/T or T/T result in a large increase in the risk of this subtype of AML, which supply some new evidenves for the theory of multistep process of leukemogenesis. Our results also showed that the cytogenetic background is different among myeloid tunours.