title: Polymorphisms in XPC, XPD and XPG DNA repair genes and leukemia risk in a Tunisian population.
abstract: Human DNA repair mechanisms protect the genome from DNA damage caused by endogenous and environmental agents. Polymorphisms in DNA repair genes and differences in repair capacity between individuals have been widely reported in different cancers. In this study we aimed to evaluate the associations between XPC Lys939Gln (rs2228001), XPD Lys751Gln (rs13181) and XPG Asp1104His (rs17655) polymorphisms and leukemia risk in a Tunisian population. Genotypes were determined by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) in 206 patients with leukemia and 206 healthy controls. We found increased risk of leukemia among subjects carrying the XPC 939Gln/Gln genotype (odds ratio [OR] = 2.48, 95% confidence interval [CI] = 1.353-4.560, p = 0.0042). Moreover, in subgroup analysis according to clinical types, patients with chronic myeloid leukemia (CML) showed a higher risk than patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) (OR = 3.87, 95% CI = 1.820-8.237, p = 0.0003). However, the XPD 751Gln allele may be protective against CML and AML development, and no significant differences in genotype frequencies were observed for the XPG gene between patients and controls. Further studies with larger samples and risk factor information are needed.
authors.affiliation: Laboratory of Molecular and Cellular Hematology, Pasteur Institute of Tunis, University of Tunis El Manar , Tunis , Tunisia.
authors.forename: Kais
authors.initials: K
authors.lastname: Douzi
authors.forename: Slah
authors.initials: S
authors.lastname: Ouerhani
authors.forename: Samia
authors.initials: S
authors.lastname: Menif
authors.forename: Ines
authors.initials: I
authors.lastname: Safra
authors.forename: Salem
authors.initials: S
authors.lastname: Abbes
mesh_terms: D000208:Acute Disease; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics*; D004720:Endonucleases / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D007938:Leukemia / Q000145:classification / Q000235:genetics*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics; D007951:Leukemia, Myeloid / Q000235:genetics; D015810:Linkage Disequilibrium; D009687:Nuclear Proteins / Q000235:genetics*; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics; D012307:Risk Factors; D014157:Transcription Factors / Q000235:genetics*; D014416:Tunisia; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics*; D000099250:DNA Excision Repair Protein ERCC-5
chemical_list: D004268:DNA-Binding Proteins; D004720:Endonucleases; D009687:Nuclear Proteins; D014157:Transcription Factors; D051759:Xeroderma Pigmentosum Group D Protein; D000099250:DNA Excision Repair Protein ERCC-5; C086984:XPC protein, human; C497292:ERCC2 protein, human
keywords: ALL; AML; CML; DNA repair gene; Polymorphisms; XPC; XPD; XPG