The Genotype Distribution of the XRCC1, XRCC3, and XPD DNA Repair Genes and Their Role for the Development of Acute Myeloblastic Leukemia

Abstract

The distribution of XRCC1Arg 339Gln genotypes showed a significant difference between patients and controls (p=0.025). The presence of at least one XRCC1 399Gln allele indicated an increased risk of AML and the proportion of AML patients homozygous for the Gln/Gln allele was significantly higher than in the control group (p=0.025). However, distributions of the XRCC3 Thr241Met, XPD Lys751Gln, and NQO1Pro 187Ser genotypes were not significantly different between patients and controls. Combined analysis of the studied DNA repair gene polymorphisms did not show an interaction with the detoxification NQO1 Pro187Ser polymorphism.

Polymorphism ofXRCC1,XRCC3, andXPDGenes and Risk of Chronic Myeloid Leukemia

“…Similar results were also reported in previous studies, in which XPD Lys751Gln variant genotypes were shown to be risk factors for AML [37] and acute lymphoid leukemia [38]. These findings are not in agreement with the study conducted by Sorour et al, in which they found no differences in the frequency of the XPD Lys751Gln polymorphism between AML patients and controls [35]. …”

“…Single-nucleotide polymorphisms (SNPs) of XPD gene, such as Arg156Arg, Asp312Asn, and Lys751Gln, have been studied in relation to lung cancer [32] and colorectal cancer [28, 34]. In the last years XPD Lys751Gln polymorphism has been investigated in different hematological malignancies, such as acute myeloid and lymphoblastic leukemia, but with contradictory results [35–41]. …”

Replication analysis confirms the association of several variants with acute myeloid leukemia in Chinese population

“…The two published GWASs have provided the unambiguous evidence that several common genetic variations influence the risk of ALL (Treviño et al 2009;Papaemmanuil et al 2009), although several replication studies in ALL were later reported; however, the role of these SNPs in the susceptibility to AML is rarely investigated (Sorour et al 2013;Pakakasama et al 2007;Lightfoot et al 2010). In our study, we evaluated the association of these SNPs with AML risk in an independent case-control study with 545 AML cases and 1034 controls in a Chinese population and found that seven SNPs (rs2191566, rs10873876, rs9290663 and rs11155133 in additive model and rs2239633, rs10821936 and rs2242041 in other genetic models) were significantly associated with altered risk of AML.…”

“…Despite differences in the pathogenesis, AML and ALL sometimes share some genetic factors. For example, XRCC1 (X-ray repair cross-complimenting group 1 gene) 399Gln allele could increase risk of both AML (Sorour et al 2013) and ALL (Sorour et al 2013;Pakakasama et al 2007), and MTR (5-methyltetrahydrofolate-homocysteine methyltransferase) 2756GG genotype showed similar effect on both acute leukemia subtypes (Lightfoot et al 2010).…”

DNA repair genes XPD and XRCC1 polymorphisms and risk of end-stage renal disease in Egyptian population

“…11,12 SNPs of XPD gene have been studied in relation to lung cancer 13 and colorectal cancer, 14,15 cataract and glaucoma development; 16,17 also, it has been investigated in different hematological malignancies, such as acute myeloid and lymphoblastic leukemia. [18][19][20] X-ray cross-complementing group 1 (XRCC1), a DNA repair protein involved in single-strand breaks and BER pathway, has been reported to be responsible for the efficient repair of DNA damage caused by active oxygen, ionization and alkylating agents. 21 It is a multidomain protein that interacts with the nicked DNA and participates with at least three different enzymes, poly-ADP-ribose polymerase, DNA ligase III and DNA polymerase b, to repair single-strand breaks.…”