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.
Subject(s)
DNA-Binding Proteins/genetics , Endonucleases/genetics , Leukemia, Myeloid, Acute/genetics , Nuclear Proteins/genetics , Polymorphism, Genetic/genetics , Transcription Factors/genetics , Xeroderma Pigmentosum Group D Protein/genetics , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/genetics , Case-Control Studies , DNA Repair , Female , Follow-Up Studies , Genetic Predisposition to Disease , Genotype , Humans , Leukemia, Myeloid, Acute/epidemiology , Male , Middle Aged , Neoplasm Staging , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , Prognosis , Risk Factors , Romania/epidemiology , Survival Rate , Young AdultABSTRACT
Oxidative damage at the DNA level may be promoted by high levels of reactive oxygen species (ROS), leading to genomic instability and increased neoplastic risk. Superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase (CAT) enzymes are implicated in the prevention of DNA damage by ROS. The aim of the study was to investigate the relationships between CAT C262T, GPX1 Pro198Leu, MnSOD Ala16Val, GSTM1, GSTT1, and GSTP1 Ile105Val polymorphisms and the risk of CML. No association was observed between CML and variant genotypes of GPX1, MnSOD, GSTM1, and GSTT1 polymorphisms in any of the investigated cases. Our study suggests that the homozygous variant genotype of the GSTP1 Ile105Val gene polymorphisms may be associated with the risk of developing CML (OR = 2.5; 95% CI = 1.08-5.7; P value = 0.02), while the heterozygous genotype of the CAT C262T polymorphism seems to have a protective effect against CML (OR = 0.59, 95% CI = 0.39-0.89, P value = 0.01). In most cases, no association was found between laboratory parameters and prognostic factors and the variant genotype of investigated gene polymorphisms. We concluded that CAT, GPX, MnSOD, GSTM1, and GSTT1 gene polymorphisms are not associated with the risk of CML. Variant genotype of the GSTP1 Ile105Val gene polymorphisms may contribute to the risk of developing CML.
Subject(s)
Catalase/genetics , Glutathione Peroxidase/genetics , Glutathione Transferase/genetics , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/enzymology , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Superoxide Dismutase/genetics , Case-Control Studies , Female , Gene Frequency , Genetic Predisposition to Disease , Genotype , Glutathione S-Transferase pi/genetics , Humans , Male , Middle Aged , Oxidative Stress , Polymorphism, Genetic , Risk Factors , Glutathione Peroxidase GPX1ABSTRACT
The genetic polymorphisms of X-ray repair cross complementing group 1 (XRCC1), X-ray repair cross complementing group 3 (XRCC3), and xeroderma pigmentosum complementation group D (XPD) repair genes may lead to genetic instability and leukemogenesis. The purpose of the study was to evaluate the association between XRCC1 Arg399Gln, Arg280His and Arg194Trp, XRCC3 Thr241Met, and XPD Lys751Gln polymorphisms and the risk of developing CML in Romanian patients. A total of 156 patients diagnosed with CML and 180 healthy controls were included in this study. We found no association between CML and XRCC1 or XRCC3 variant genotypes in any of the investigated cases. A significant difference was observed in the variant genotype frequencies of the XPD Lys751Gln polymorphism between the patients with CML and control group (for variant homozygous genotypes, OR = 2.37; 95% CI = 1.20-4.67; P value = 0.016 and for combined heterozygous and variant homozygous genotypes, OR = 1.72; 95% CI = 1.10-2.69; P value = 0.019). This was also observed when analyzing the variant 751Gln allele (OR = 1.54; 95% CI = 1.13-2.11; P value = 0.008). Our results suggest that the XPD Lys751Gln variant genotype increases the risk of CML.
