Risk effects of XRCC1 Arg399Gln and XPD Lys751Gln gene polymorphisms in <em>de novo</em> acute myeloid leukemia – A study from India

Abstract

Defects in the DNA repair pathway are connected to many malignancies including leukemia. Variability in the repair rates leading to genotoxic damage have been shown to be associated with polymorphisms of XRCC1 Arg399Gln and XPD Lys 751 Gln, involved in the base excision repair and the nucleotide excision repair pathway. The present study focused on the risk effects of these polymorphisms in acute myeloid leukemia (AML). Genotypes were analyzed in 211 AML patients and control samples using polymerase chain reaction and restriction fragment length polymorphism. Logistic regression analysis was carried out to find the association of various polymorphisms with susceptibility to AML. Kaplan-Meier survival analysis was carried out to find the influence of these polymorphism on patients overall survival. The carriers of XRCC1 399 GA genotype were at increased risk for AML than with carriers of GG genotype. Subjects carrying XPD 751 AC as well as CC genotype were at an increased risk for the onset of the disease. The CC genotype was found to be having the higher risk than other genotypes with an OR of 5. 29 (P < 0. 001). In the combination group XRCC1 399 GG/ XPD 751 AC + CC and XRCC1 399 GA+AA/ XPD 751 AA show an increased risk for AML with P value 0. 010 and 0. 004 respectively. While a 6.8 fold increased risk was shown by the both variant genotype combination. A significant association for the XRCC and XPD genotype with overall survival was not detected in the present study. Our findings suggests that genetic polymorphism in the DNA repair genes may modulate susceptibility to AML.