Polymorphisms of the DNA repair genes (APE1, XPD, and RAD51) and the risk of developing cytogenetic abnormalities in a cohort of Egyptian patients with newly diagnosed AML

Abstract

Abstract Background Genetic alterations of the DNA repair genes might decrease the efficiency of DNA repair mechanisms and increase susceptibility to cancers such as acute myeloid leukemia (AML). Objectives The purpose of the present study was to detect the association of APE1Asp148Glu; rs1130409, XPD Lys751Gln;rs13181 & RAD51 G135C;rs1801320 polymorphisms with the risk of developing abnormal cytogenetics in a sample of newly diagnosed AML Egyptian patients. Methods: The target genetic polymorphisms were determined by polymerase chain reaction and restriction fragment length polymorphism (PCR –RFLP) in 101 AML blood samples comprising 70 cases with normal cytogenetics and 31 cases with abnormal cytogenetics. Results: The genotypic variants of APE1Asp148Glu; rs1130409 polymorphism (T/G,G/G,T/G+G/G) were significantly associated with cytogenetic abnormalities than normal cytogenetics in the studied de novo AML cases {P-0.022,OR:3.463,95%CI:1.199-10.002;P-0.042,OR:3.85,95%CI:1.049-14.124;P-0.01,OR:3.568,95%CI:1.299-9.797}, respectively. The combined APE1 mutants (T/G+G/G) were more likely to be associated with t(15;17){P-value0.02,OR:10.08,95%CI:1.23-82.41}. The association of XPD Lys751Gln combined mutants (A/C+C/C) and RAD1 G135C(G/C+C/C) in AML cases with abnormal cytogenetics were not significantly different from those with normal cytogenetics. Conclusions: APE1Asp148Glu; rs1130409 polymorphism in AML may be associated with the development of favourable cytogenetic abnormalities, especially t(15; 17) .This association might affect AML prognosis but further large sample studies including AML cases with adverse cytogenetics should be performed.