title: Influence of XPC, XPD, XPF, and XPG gene polymorphisms on the risk and the outcome of acute myeloid leukemia in a Romanian population.
abstract: XPC, XPD, XPF, and XPG genes are implicated in the nucleotide excision repair (NER) system. Gene polymorphisms in NER repair system may influence the individual's capacity to recognize and repair DNA lesions, thus increasing the cancer risk. We hypothesized that these gene polymorphisms might influence the probability of developing acute myeloid leukemia (AML). We investigated the XPC, XPD, XPF, and XPG gene polymorphisms in 108 AML cases and 163 healthy controls. Also cytogenetic analyses besides FLT3 and DNMT3A mutations status were investigated. We found that variant genotypes (heterozygous and homozygous) of XPD 2251A > C and 22541A > C and the heterozygous genotype of XPG 3507G > C were associated with the risk of developing AML (OR = 2.55; 95% CI = 1.53-4.25; p value <0.001; OR = 1.66, 95 % CI = 1.02-2.72; p value = 0.047, and OR = 2.36; 95 % CI = 1.32-4.21; p value = 0.004, respectively). No association was found between white blood cell counts, FLT3, DNMT3A mutations, cytogenetic risk group, and variant genotypes of none of the analyzed polymorphisms. Variant homozygous XPF 673C > T genotype was associated with higher dose of cytosine arabinoside treatment administrated to AML patients (p value = 0.04). No differences were found regarding survival time and variant genotype in the investigated gene polymorphisms with the exception of XPD 2251A > C. In conclusion, XPD 22541A > C, XPD 2251A > C, and XPG 3507G > C gene polymorphisms confer susceptibility to AML, while XPC 2920A > C, XPF-673C > T, XPF 11985A > G are not associated with AML.
authors.affiliation: Department of Medical Genetics, University of Medicine and Pharmacy Tirgu Mures, 38 Gh Marinescu St, 540139, Tirgu Mures, Romania. claudia.banescu@gmail.com.
authors.forename: Claudia
authors.initials: C
authors.lastname: Bănescu
authors.affiliation: Department of Medical Informatics and Biostatistics, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, 8 Victor Babes St, 400012, Cluj-Napoca, Romania.
authors.forename: Mihaela
authors.initials: M
authors.lastname: Iancu
authors.affiliation: Department of Medical Genetics, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, 8 Victor Babes St, 400012, Cluj-Napoca, Romania.
authors.forename: Adrian P
authors.initials: AP
authors.lastname: Trifa
authors.affiliation: Department of Laboratory Medicine, University of Medicine and Pharmacy Tirgu Mures, 38 Gh Marinescu St, 540139, Tirgu Mures, Romania.
authors.forename: Minodora
authors.initials: M
authors.lastname: Dobreanu
authors.affiliation: Department of Medical Genetics, University of Medicine and Pharmacy Tirgu Mures, 38 Gh Marinescu St, 540139, Tirgu Mures, Romania.
authors.forename: Valeriu G
authors.initials: VG
authors.lastname: Moldovan
authors.affiliation: Pediatric Clinic, University of Medicine and Pharmacy Tirgu Mures, 38 Gh Marinescu St, 540139, Tirgu Mures, Romania.
authors.forename: Carmen
authors.initials: C
authors.lastname: Duicu
authors.affiliation: Department of Medical Genetics, University of Medicine and Pharmacy Tirgu Mures, 38 Gh Marinescu St, 540139, Tirgu Mures, Romania.
authors.forename: Florin
authors.initials: F
authors.lastname: Tripon
authors.affiliation: Department of Medical Genetics, University of Medicine and Pharmacy Tirgu Mures, 38 Gh Marinescu St, 540139, Tirgu Mures, Romania.
authors.forename: Andrei
authors.initials: A
authors.lastname: Crauciuc
authors.affiliation: Al Jawhara Center for Molecular Medicine, College of Medicine, Arabian Gulf University, P.O. Box 26671, Manama, Bahrain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Skypnyk
authors.affiliation: Department of Medical Genetics, University of Medicine and Pharmacy Tirgu Mures, 38 Gh Marinescu St, 540139, Tirgu Mures, Romania.
authors.forename: Alina
authors.initials: A
authors.lastname: Bogliș
authors.affiliation: Hematology Clinic 2, University of Medicine and Pharmacy Tirgu Mures, 38 Gh Marinescu St, 540139, Tirgu Mures, Romania.
authors.forename: Erzsebeth
authors.initials: E
authors.lastname: Lazar
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics; D016022:Case-Control Studies; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics*; D004720:Endonucleases / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D011379:Prognosis; D012307:Risk Factors; D012383:Romania / Q000453:epidemiology; D015996:Survival Rate; D014157:Transcription Factors / Q000235:genetics*; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics*; D055815:Young Adult; D000099250:DNA Excision Repair Protein ERCC-5
chemical_list: D014408:Biomarkers, Tumor; 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; C095888:xeroderma pigmentosum group F protein; C086984:XPC protein, human; C497292:ERCC2 protein, human
keywords: AML; Gene polymorphism; XPC; XPD; XPF; XPG