Detection of XRCC1 gene polymorphisms in Egyptian patients with acute myeloid leukemia
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Mona Salah El-Din & Hanan Raslan & Samah Abdel-Hamid & Manal Makhlouf
- چاپ و سال / کشور: 2010
Description
XRCC1 is a polymorphic gene belonging to one of the major deoxyribonucleic acid (DNA) repair pathways. XRCC1 is involved in base excision repair (BER) and the repair of single-strand breaks. Several variants of XRCC1 have been described, including one affecting codon 399 in exon 10 that results in an arginine (Arg) to glutamine (Gln) substitution and one affecting codon 194 in exon 6 that results in an Arg to tryptophan (Trp) substitution. The aim of this study was to determine the presence of these polymorphisms in the Egyptian population and to define their role in modulating susceptibility to development of acute myeloblastic leukemia (AML) using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique in 40 de novo AML patients and 20 controls. The risk of development of AML was found to be significantly increased when variant XRCC1-399 (Arg/Gln) is present (P value 0.025). Moreover, the risk of AML development was found to be significantly increased when variant XRCC1-194 (Arg/Trp) is present (P value 0.002), whereas the risk of AML development is even higher when both variants XRCC1-Arg-399 Gln and Arg-194 Trp alleles are present (odds ratio [OR] 6.15 and 4.00 and 95% CI 1.88–20.05 and 1.13–14.08, respectively), presumably because an increase in DNA damage significantly increases the risk of development of AML, and the phenotypes, as a result, interact to increase this risk. These results strongly suggest that BER pathway, notably XRCC1, is important in the pathogenesis of de novo AML.
Comp Clin Pathol DOI 10.1007/s00580-010-1120-4 Received: 29 July 2010 / Accepted: 8 October 2010
