XPD Lys751Gln Polymorphisms Research Articles

Abstract 3046: Association of XRCC1 Arg194Trp polymorphism and XPD Lys751Gln polymorphism with biochemical parameters, severity and risk of prostate cancer in Bangladesh Population

Abstract a)To evaluate the association between x-ray cross-complementing gene 1 (XRCC1) polymorphism Arg194Gln and xeroderma pigmentosum group D (XPD) polymorphism Lys751Gln with severity and risk of prostate cancer as well as with biochemical parameters of prostate cancer patients in Bangladesh population. b) Blood samples and data were collected from 132 prostate cancer patients and 135 healthy controls among Bangladesh population. Genotype analysis was done by the PCR-RFLP method. Statistical analysis was performed using GraphPad Prism 9.4.1 software. c) Only the recessive model, that is, carrying two copies of the XRCC1 194 codon Trp allele was positively associated with prostate cancer, with an OR of 7.50 (95% CI, 1.227-85.12; p=0.035). No association was found between the XPD variants with prostate cancer risk. Keeping the wild type and heterozygous genotype as a reference, the combined effects of the XRCC1 codon 194 Arg/Arg and the XPD codon 751 Gln/Gln genotype were found to be significantly associated with prostate cancer risk with an OR of 3.25 (95% CI, 1.39-8.20; p=0.006). XRCC1 194 Trp/Trp genotype was significantly associated with obstructive features, such as hematuria and creatinine levels of the prostate cancer patients (P<0.05). Moreover, the homozygous mutant Gln/Gln genotype of XPD gene was also significantly associated with creatinine levels in prostate cancer patients. No association was found between any of the variants of XRCC1 and XPD with invasiveness, tumor grade, prostate ultrasound scan results, digital rectal examination, Urine R/E or Prostate Specific Antigen (PSA) results (P>0.05). d) Only the XRCC1 codon 194 Trp allele showed a modest association with prostate cancer risk with an 8.19-fold increased risk when two copies of the allele were present. When both alleles- XRCC1 codon 194 and XPD codon 751 Gln -were present in their homozygous states, the risk for prostate cancer increased by 3.2-folds. Our results showed a significant association between XRCC1 194 Trp/Trp with obstructive features and and levels of creatinine in prostate cancer patients of Bangladeshi men. Citation Format: Nafisa Ahmed, MD. Ariful Islam, M. Mahboob Hossain, Yearul Kabir. Association of XRCC1 Arg194Trp polymorphism and XPD Lys751Gln polymorphism with biochemical parameters, severity and risk of prostate cancer in Bangladesh Population [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3046.

DNA repair gene (XRCC1 and XPD) polymorphism and risk of primary ovarian failure.

DNA repair genes may be related with the onset of primary ovarian failure (POF). The study was planned to investigate whether the polymorphisms in the DNA repair genes modulate the risk of POF. This prospective study included 25 women diagnosed with POF and 25 healthy controls. The genotyping and allele of XRCC1 and XPD genes were determined by using Polymerase Chain Reaction and fluorescence melting curve analysis. The genotype and allele distribution of the Arg194Trp and Arg399Lys polymorphism of the XRCC1 gene did not differ statistically between those of the POF and control groups. The frequency of the C (Gln) allele was significantly lower in patients diagnosed with POF when compared to that in healthy controls [48% vs. 76%, p=0.040, OR: 3.43 (CI: 1.03-11.48)]. The Lys/Lys genotype for XPD-Lys751Gln polymorphism in patients diagnosed with POF was more common than in healthy controls (p=0.028, 52% vs. 24%). The genotype distribution and allele frequency of XPD-Lys751Gln, XRCC1-Arg194Trp and XRCC1-Arg399 Gln did not regulate the risk of developing POF. Gln/Gln+Lys/Gln and XPD-Lys751Gln polymorphism may have a possible protective role against the development of POF.

Polymorphism of the DNA repair gene XDP increases the risk of systemic lupus erythematosus but not multiple sclerosis in the Iranian population

BackgroundXeroderma pigmentosum group D ( XPD ) is an essential component of the nucleotide excision repair (NER) pathway, which can play a major role in DNA repair processes. A deficiency in this pathway was suggested as a causative factor of autoimmune diseases. Therefore, the current study aimed to investigate the relationship between XPD Lys751Gln polymorphism (rs13181) as one of the most common XDP polymorphisms and the risk of two important auto-immune diseases,namely systemic lupus erythematosus (SLE) and multiple sclerosis (MS) in the Iranian population. Methods165 SLE patients and 165 age- and gender-matched healthy controls, and 150 MS patients and 150 age- and gender-matched healthy controls were genotyped for XPD rs13181 A/C polymorphism using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. ResultsThe results of the present study have indicated that both C allele frequency ( P = 0.012; odds ratio: 1.5; 95% confidence interval: 1.1–2.07) and CC genotype ( P = 0.007; odds ratio: 2.46; 95% confidence interval: 1.2–4.7) in SLE patient were significantly higher than those in control group. Furthermore, there were no significant differences between MS patients and normal subjects concerning the genotype and the allele frequencies. ConclusionOur findings suggested that XPD rs13181 A/C polymorphism may be a crucial risk factor for the development of SLE but not MS in Iranian patients.

Assessment on the influence of TLR4 and DNA repair genes in laryngeal cancer susceptibility: a selective examination in a Romanian case control study

Abstract Background: Tumor characterization through the study of molecular biology has become an invaluable tool in understanding cancer development and evolution due to its relationship with chromosomal mutations, alterations or aberrations. The purpose of this study was to investigate the involvement of genes such as TLR-4 and DNA repair pathways (XRCC1 and XPD) in laryngeal cancer susceptibility in a Romanian population. Method: We performed a case-control study on 157 laryngeal cancer patients and 101 healthy controls. Genetic testing was carried out using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism. Results: We identified the Gln allele of the XPDLys751Gln polymorphism as an individual risk factor in laryngeal cancer development (Gln vs Lys, adjusted OR=1.65, 95%CI=1.13–2.40, P=0.008). Subjects with the mutant homozygote variant (Gln/Gln) had a two fold increase in cancer risk (adjusted OR=2.18, 95%CI=1.06–4.47, p=0.028) when compared to the reference wild type genotype (Lys/Lys). Stratification by sex and age, identified males under 62 years as the most susceptible group with an almost three fold risk (adjusted OR=2.94, 95%CI=1.31–6.59, p=0.007) for the dominant model (Lys/Gln+Gln/Gln). No associations were found for TLR-4Thr399Ile, XRCC1Arg194Trp and XRCC1Arg399Gln. Conclusion: The results of the study show that the XPDLys751Gln polymorphism may be among other independent risk factors for developing laryngeal cancer where as TLR-4Thr399Ile, XRCC1Arg194Trp and XRCC1 Arg399Gln show no such association. However, we consider the relative small number of the subjects selected for this analyses a possible limitation towards the real influence the obtain results may pertain in laryngeal cancer evolution.

Association of XPD Lys751Gln gene polymorphism with susceptibility and clinical outcome of colorectal cancer in Pakistani population: a case-control pharmacogenetic study.

XPD Lys751Gln polymorphism may modulate inter-individual variation in repair capacity of DNA, which may enhance a person's susceptibility to develop colorectal cancer (CRC). The analysis of XPD Lys751Gln polymorphism may provide important information for identifying high-risk individuals and for selecting the most appropriate treatment for poor prognostic CRC patients. The overall objective was to find out the association of XPD Lys751Gln gene polymorphism with the risk of having a colorectal cancer and the ultimate clinical outcomes. In this study a total of 300 subjects (CRC and Controls), were genotyped for XPD Lys751Gln. Using PCR-RFLP methods, the association of XPD Lys751Gln gene polymorphism with the risk of having a colorectal cancer was studied. In addition to overall risk assessment, genotyping results were also investigated with respect to the lifestyle risk factors, patients treated with oxaliplatin-based chemotherapy and clinicopathological characteristics. The overall correlation between the XPD Lys751Gln genetic variation and the CRC risk was observed to be significant with both the homozygous variant genotype Gln/Gln as well as heterozygous genotype Lys/Gln being associated with the increased risk of CRC. Additional stratified analyses revealed that XPD Lys751Gln variants remarkably increased risk of CRC in males and younger individuals (≤ 50years), Naswar users (8.09-fold) and high intake of red meat. Our findings suggest that the relationship between the XPD Lys751Gln variants and lifestyle factors modulates the risk for CRC in Pakistani population.

Impact of DNA Repair Genes Polymorphisms on Incidence and Prognosis of Breast Cancer in an Egyptian Cohort

Background: Sporadic breast cancer might be caused by low-penetrance genes, including genes constituting the DNA repair pathways. Defective DNA repair is a common imprint of cancer that promotes the accretion of DNA errors and genomic instability. The clustering of damage in DNA may stimulate breast carcinogenesis. Aims: The goal of the study is to evaluate the role of single nucleotide polymorphisms in DNA repair genes XRCC1 Arg399Gln, XPD Lys751Gln, RAD51 G135C and XRCC3 Thr241Met as genetic indicators of susceptibility to breast cancer and to evaluate their role in treatment outcome. Methodology: The study included 248 females diagnosed with primary breast cancer and 232 normal healthy females. Patients were clinically followed up for 5 years after completing chemotherapy. Genomic DNA was isolated and the four polymorphisms under investigation were assessed by PCR-RFLP technique. Findings: XRCC1 399Gln, XPD 751Gln and XRCC3 241Met alleles were significantly associated with breast cancer risk (OR = 2.63, 2.17 and 3.21; respectively), with carriers having lower disease free survival (DSF). When grouping patients based on the number of affected genotypes they carry, DFS decreased as the number of affected genotypes increased (PaccumConclusion: XRCC1 Arg399Gln, XPD Lys751Gln and XRCC3 Thr241Met polymorphisms may take a significant part in sporadic breast cancer as risk factors and in prognosis, where patients carrying XRCC1 Arg/Arg, XPD Lys/Lys and XRCC3 Thr/Thr genotypes had significantly diminished risk for breast cancer and higher DFS. DFS decreased as the number of affected genotypes increased. But RAD51 5'UTR G135C polymorphism did not associate with either risk or prognosis of breast cancer.

Haplotype CGC from XPD, hOGG1 and ITGA2 polymorphisms increases the risk of nasopharyngeal carcinoma in Malaysia.

Background8-oxoG, a common DNA lesion resulting from reactive oxygen species (ROS), has been shown to be associated with cancer initiation. hOGG1 DNA glycosylase is the primary enzyme responsible for excision of 8-oxoG through base excision repair (BER). Integrins are members of a family of cell surface receptors that mediate the cell-cell and extracellular matrix (ECM) interactions. Integrins are involved in almost every aspect of carcinogenesis, from cell differentiation, cell proliferation, metastasis to angiogenesis. Loss of ITGA2 expression was associated with enhanced tumor intravasation and metastasis of breast and colon cancer. XPD gene encodes DNA helicase enzyme that is involved in nucleotide excision repair (NER). It is shown in previous research that XPD homozygous wildtype Lys/Lys genotype was associated with higher odds of NPC.MethodsWe conducted a 1 to N case-control study involving 300 nasopharyngeal carcinoma (NPC) cases and 533 controls matched by age, gender and ethnicity to investigate the effect of hOGG1 Ser326Cys, ITGA2 C807T and XPD Lys751Gln polymorphisms on NPC risk. Linkage disequilibrium and haplotype analysis were conducted to explore the association of allele combinations with NPC risk. Restriction fragment length polymorphism (RFLP-PCR) was used for DNA genotyping.ResultsNo significant association was observed between hOGG1 Ser326Cys and ITGA2 C807T polymorphisms with NPC risk after adjustment for age, gender, ethnicity, cigarette smoking, alcohol and salted fish consumption. Lys/Lys genotype of XPD Lys751Gln polymorphism was associated with increased NPC risk (OR = 1.60, 95% CI = 1.06–2.43). Subjects with history of smoking (OR = 1.81, 95% CI = 1.26–2.60), and salted fish consumption before age of 10 (OR = 1.77, 95% CI = 1.30–2.42) were observed to have increased odds of NPC. The odds of developing NPC of CGC haplotype was significantly higher compared to reference AGC haplotype (OR = 2.20, 95% CI = 1.06–4.58).ConclusionThe allele combination of CGC from hOGG1, ITGA2 and XPD polymorphisms was significantly associated with increased odds of NPC.

The Investigation of Polymorphisms in DNA Repair Genes (XRCC1, APE1 and XPD) in Women with Polycystic Ovary Syndrome

Background:PCOS was reported to arise from the interaction of genetic and environmental factors. Some studies reported that women with PCOS have DNA damage and chromosome breakage. Such studies bring to mind the genes that are involved in DNA repairing. At present, several DNA repair genes and, as products of these genes, certain polymorphisms that alter the activity of proteins are known in the literature. The aim of this dissertation is to study the genomic instability that have been reported in PCOS cases along with the relationship between XRCC1 Arg194Trp, XRCC1 Arg399Gln, APE1 Asp148Glu, and XPD Lys751Gln polymorphisms in order to contribute to the pathogenesis of PCOS.Methods:Polymorphisms in DNA repair genes have been associated with the increased risk of various diseases and could also be related to the etiology of PCOS. Therefore, we conducted a study including 114 women with PCOS and 91 controls. These polymorphisms were determined by quantitative real time PCR and melting curve analysis using LightCycler.Results:Comparing the control groups at the end of the study, the results have not shown any statistically significant difference as far as XRCC1 Arg194Trp, XRCC1 Arg399Gln, and XPD Lys751Gln polymorphisms are concerned. However, there were notable differences between the groups in terms of APE1 Asp148Glu polymorphism. Associated with this condition, it has been noted that both mutant allele (Glu) frequency (37.72 % in the study group; 19.23% in the control group, p=0.0001) and homozygous mutant genotype (Glu/Glu) frequency (%12.28 in the study group; %6.60 in the control group, p=0.015) have been higher in the study group.

POLYMORPHISM OF DNA REPAIR GENE XPD Lys751Gln AND CHROMOSOME ABERRATIONS IN LYMPHOCYTES OF THYROID CANCER PATIENTS EXPOSED TO IONIZING RADIATION DUE TO THE CHORNOBYL ACCIDENT

XPD Lys751Gln polymorphisms were detected by polymerase chain reaction in 102 TC patients including 38 patients exposed to ionizing radiation due to Chornobyl disaster (Chornobyl recovery workers, evacuees, and the residents of contaminated areas), 64 patients without history of ionizing radiation exposure and 45 healthy residents of Ukraine as control group. In homozygous carriers of the minor allele XPD Gln751Gln, exposed to ionizing radiation, the significantly increased risk of TC (odds ratio = 3.66; p = 0.03; 95% confidence interval 1.04-12.84) was found. Among evacuees and residents of contaminated areas, homozygous carriers of the minor allele variants of XPD gene were characterized by the high level of spontaneous chromosome aberrations. TC patients without history of ionizing radiation exposure, being homozygous carriers of the allele XPD Lys751Lys, had significantly reduced frequency of chromosome-type aberrations. The carriage of homozygous minor allele of DNA repair gene XPD Gln751Gln is a risk factor for TC in persons from Ukrainian population exposed to ionizing radiation and is associated with the increased levels of chromosomal instability. This article is a part of a Special Issue entitled "The Chornobyl Nuclear Accident: Thirty Years After".

DNA repair genes polymorphisms and risk of colorectal cancer in Saudi patients

Background and study aimsPolymorphisms in the DNA repair genes may influence individual capacity to repair DNA damage, which may be associated with increased genetic instability and carcinogenesis. Our aim was to evaluate the relation of genetic polymorphisms in 2 DNA repair genes, XPD Lys751Gln and XRCC1 (A399G), with colorectal cancer (CRC) susceptibility. We further investigated the potential effect of these DNA repair variants on clinicopathological parameters of CRC patients. Patients and methodsBoth XPD and XRCC1 polymorphisms were characterised in one hundred CRC patients and one hundred healthy controls who had no history of any malignancy by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method and PCR with confronting two-pair primers (PCR–CTPP), using DNA from peripheral blood in a case control study. ResultsOur results revealed that the frequencies of GG genotype of XRCC1 399 polymorphism were significantly higher in the CRC patients than in the normal individuals (p⩽0.03), and did not observe any association between the XPD Lys751Gln polymorphism and CRC risk. We found association between both XRCC1 A399G polymorphisms and histological grading of disease. ConclusionOur results suggested that, XRCC1 gene is an important candidate gene for susceptibility to colorectal carcinoma.

XRCC3 Thr241Met and XPD Lys751Gln gene polymorphisms and risk of clear cell renal cell carcinoma.

In the last decade, an increasing number of polymorphisms in DNA repair genes have been identified and their involvement in carcinogenesis was studied. Despite the fact that XRCC3 and XPD DNA repair genes association with several types of cancer was widely studied, their role in the development of clear cell renal cell carcinoma (CCRCC) has not been established in the European population. The objective of this study was to investigate the association of XRCC3 Thr241Met and XPD Lys751Gln gene polymorphisms with the risk of CCRCC and the association between these genotypes and CCRCC histopathological prognostic factors (pathologic stage, Fuhrman grade, tumor diameter). This study included 73 patients with CCRCC and 100 healthy individuals without cancer. We used the PCR-RFLP method to determine XRCC3 and XPD genotypes. The XPD 751 variant genotype (Lys/Gln) was more frequent in CCRCC patients than in healthy individuals (OR = 2.92, 95%CI: 1.47-5.79, p= 0.001). Regarding the XRCC3 Thr241Met/XPD Lys751Gln combined genotypes a significant difference was found between patients and controls for Thr/Thr+Lys/Gln (OR = 5.44, 95%CI: 2.09-14.15, p= 0.0003) and for Thr/Met+Gln/Gln (OR = 11.2, 95%CI: 1.95-100.4, p= 0.01).No association was found between any of the studied genotypes and histopathological prognostic factors of CCRCC. Our findings indicate that XPD Lys751Gln polymorphism may be a risk factor for CCRCC. Regarding the XRCC3 Thr241Met polymorphism, an association with CCRCC was found only in XRCC3 Thr241Met/XPD Lys751Gln combined genotypes.

Single nucleotide polymorphisms in DNA repair genes and the risk of laryngeal cancer: A meta-analysis.

Laryngeal cancer is the most common type of head and neck cancer with poor prognosis and high relapse rate. Several genes involved in DNA repair pathways have been identified for their potential role in laryngeal cancer risk. However, the results remain inconclusive. The aim of this study was to investigate the association between polymorphisms of XRCC1 Arg399Gln, XRCC3 Thr241Met, and XPD Lys751Gln and laryngeal cancer risk. Relevant case-control studies published between 2000 and 2015 were retrieved. The odds ratio (OR) with its 95% confidence interval (CI) were employed to calculate the strength of correction. Finally, total 16 articles (8 for XRCC1 Arg399Gln variant, 8 for XRCC3 Thr241Met variant and 7 for XPD Lys751Gln variant) were screened out, including 2242 laryngeal cancer cases and 3811 matched controls. Overall, our results found that only AA genotype of the XRCC1 gene Arg399Gln polymorphism under the homozygous model was associated with increased the risk of patients with laryngeal cancer (AA vs. GG: OR=1.29, 95% CI=1.00-1.65, P=0.05). This significant relationship was not detected between XRCC3 Thr241Met, XPD Lys751Gln polymorphisms and laryngeal cancer risk (P>0.05). In conclusions, our results suggested that XRCC1 gene Arg399Gln polymorphism might be a risk factor for laryngeal cancer. Future studies with large-scales, more ethnicities are still needed to further evaluate the role of these three genes mutations in laryngeal cancer susceptibility.

Association of XPD (Lys751Gln) and XRCC1 (Arg280His) gene polymorphisms in myelodysplastic syndrome

Myelodysplastic syndromes (MDSs) are heterogeneous hematopoietic disease characterized by ineffective haematopoiesis that frequently transforms into acute leukaemia. Alterations in many individual biologic pathways have been reported in MDS pathophysiology. Disease progression along the MDS, acute myeloid leukemia (AML) continuum is believed to be a consequence of stepwise accumulation of DNA mutations which infers a defect in DNA repair. The present study investigated the association between DNA repair genes (XRCC1, XRCC3, OGG1, XPD and RAD51) and the risk of developing MDS. The study was carried out in 92 primary MDS patients. The genotyping study was carried out by PCR-RFLP technique. We have studied seven single-nucleotide polymorphisms (SNPs) of five DNA repair genes (XRCC1 (Arg194Trp, Arg280His, Arg399Gln), XRCC3, XPD, RAD51 and OGG1). Significantly, a high frequency of DNA repair gene XRCC1 (Arg280His) (p=0.05) and XPD (Lys751Gln) (p=0.01) polymorphism was observed in MDS patients compared to controls. The distribution of polymorphisms in MDS subgroups showed a significant association of XRCC1 with RAEB I compared to other subgroup. Though a high frequency of XRCC1 gene polymorphism was observed in farmers and tobacco chewers, it was not statistically significant. Our study suggests that XRCC1 (Arg280His) and XPD polymorphisms are associated with risk of MDS and XRCC1 polymorphism strongly associated with advanced MDS subgroup. Hence, these polymorphisms can be used as a prognostic marker in MDS.

DNA Repair Gene Polymorphisms and Their Relation With DNA Damage, DNA Repair, and Total Antioxidant Capacity in Childhood Acute Lymphoblastic Leukemia Survivors

Oxidative stress and defective DNA repair are major contributory factors in the initiation and progression of carcinogenesis. Chemotherapy and radiotherapy cause oxidative DNA damage, consume antioxidant capacity, and impair DNA repair activity. These effects of chemotherapy and radiotherapy may be contributory factors in the development of secondary malignancy in cancer survivors. Basal, H2O2-induced, and postrepair DNA damage; urinary 8-hydroxydeoxyguanosine level as a marker of oxidatively damaged DNA; and serum total antioxidant capacity were measured; XPD Lys751Gln, XRCC1 Arg399Gln, and XRCC1 Arg194Trp polymorphisms were analyzed in childhood acute lymphoblastic leukemia (ALL) survivors. Basal and H2O2-induced DNA damage were found to be higher in the ALL survivor group versus the control group, however, there was no significant difference between the other parameters. No association was found between the examined parameters and polymorphisms of XPD 751 and XRCC1 399 and both the groups. XRCC1 194Trp allele was found to be associated with a low level of postrepair DNA damage in the ALL survivors. In conclusion, basal DNA damage and susceptibility to oxidation are high in childhood ALL survivors. This situation which may easily lead to occurrence of a secondary cancer does not seem to be a result of deficient DNA repair.

XPD Lys751Gln polymorphisms and the risk of esophageal cancer: an updated meta-analysis.

Published data regarding the association between xeroderma pigmentosum group D XPD Lys751Gln polymorphisms and esophageal cancer (EC) cancer remain controversial. The present meta-analysis aimed to obtain a more precise estimation of the relationship between XPD Lys751Gln polymorphisms and the risk of EC. All eligible case-control studies of Lys751Gln polymorphisms and susceptibility to EC were selected from PubMed, Web of Science and CNKI up to October 2013. The data were extracted, and pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. A total of 21 case-control studies from 19 reports were assessed in this meta-analysis, including 6,581 cases and 8,251 controls. There was a significant association between the XPD Lys751Gln polymorphism and the risk of esophageal cancer in the overall population (Dominant model: OR=1.30, 95%CI: 1.07-1.57, p<0.05; Lys/Gln vs. Gln/Gln: OR=1.20, 95%CI: 1.05-137, p<0.05; Gln/Gln vs. Lys/Lys: OR=1.76, 95%CI: 1.08-2.85, p=0.02; Recessive model: OR=1.48, 95%CI: 1.06-2.07, p=0.02). Similar results were found when stratified according to the cancer type, ethnicity and control source. However, no associations were found among smokers or drinkers. The results of this meta-analysis suggest that XPD Lys751Gln polymorphisms contribute to susceptibility to EC.

Research of DNA repair genes polymorphism XRCC1 and XPD and the risks of thyroid cancer development in persons exposed to ionizing radiation after Chornobyl disaster

The objective of this work was to determine and compare the features of DNA repair gene XRCC1 Arg399Gln and XPD Lys751Gln polymorphisms in patients with thyroid cancer (TC), who were exposed to ionizing radiation (IR) as a result of the Chornobyl disaster, and in patients without exposure to ionizing radiation in history. Determination of gene XRCC1 Arg399Gln and XPD Lys751Gln polymorphisms was performed by polymerase chain reaction (PCR) in 102 patients with thyroid cancer: 38 people, who were exposed to ionizing radiation due to Chornobyl disaster (members of the accident, and evacuees and residents from controlled areas contaminated with radionuclides), 64 individuals without exposure to ionizing radiation in history and 41 persons residents of Ukraine without cancer pathology in the control group. For comparison of the data on spontaneous and radiation-associated thyroid cancer and settlement of allele frequencies differences and risk of cancer pathology were used the literature data on control groups of populations of Russia, Belarus and Poland. Comparing to the literature data on XRCC1 Arg399Gln polymorphisms in radiation-exposed individuals without cancer pathology, the risk of thyroid cancer in homozygous minor allele XRCC1 Gln399Gln carriers, who were exposed to ionizing radiation was significantly increased: OR = 4,14, p = 0,001 (CI95 % 1,72-9,93). In homozygous carriers of the minor allele of the gene XPD Lys751Gln, exposed to IR, revealed increased risk of thyroid cancer: OR = 3,30, p = 0,05 (CI 95 % 0,82-14,14), when compared with the control group of Ukrainian population. The carriage of homozygous minor allele Gln399Gln XRCC1 and XPD Gln751Gln of DNA repair genes is a risk factor for thyroid cancer under the influence of ionizing radiation in research group of Ukrainian population.

Polymorphisms in XPC, XPD and XPG DNA repair genes and leukemia risk in a Tunisian population

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.

XPD Lys751Gln and Asp312Asn polymorphisms and susceptibility to skin cancer: a meta-analysis of 17 case-control studies.

Numerous studies have explored the influence of XPD Lys751Gln and/or Asp312Asn polymorphisms on skin cancer susceptibility. However, the results remain inconclusive. To derive a more precise estimation, we conducted a comprehensive search to identify all available published studies and performed a meta-analysis. Electronic literature searches of the PubMed, CBM and CNKI databases were performed up to March 2014. Odds ratios (ORs) with 95% confidence intervals (CIs) were applied to assess the strength of associations. Seventeen case-control studies were included with a total sample size of 6, 113 cases and 11, 074 controls for the XPD Lys751Gln polymorphism, and 10 studies (3, 840cases and 7, 637 controls) for the XPD Asp312Asn polymorphism were pooled for analysis. Overall, no significant associations were found between the XPD Lys751Gln polymorphism and skin cancer risk in any genetic model. On stratified analysis by tumor type, XPD Lys751Gln polymorphism was not associated with increased risk of non-melanoma skin cancer, but was significantly related with increased risk of cutaneous melanoma (Gln/Gln vs Lys/Lys: OR=1.15, 95%CI=1.02-1.29, p=0.023; dominant model: OR=1.09, 95%CI=1.01-1.18, p=0.036). For the XPD Asp312Asn polymorphism, no significant association with skin cancer risk was observed in overall or subgroup analyses. The present meta-analysis suggests that the XPD Lys751Gln polymorphism may contribute to the risk of cutaneous melanoma from currently available evidence. Further investigations are needed to obtain more insight into possible roles of these two polymorphisms in skin carcinogenesis.

Nucleotide excision repair gene polymorphisms and prognosis of non-small cell lung cancer patients receiving platinum-based chemotherapy: A meta-analysis based on 44 studies

RR, 1.22; 95% CI, 1.11-1.36; and P=0.00]. No significant association between the ERCC1 C118T/C8092A XPDLys751Gln and XPA A23G polymorphisms and tumor response was found. There was also no evidence found to support the use of the ERCC1 C118T/C8092A XPDLys751Gln and XPA A23G polymorphisms as prognostic predictors of platinum-based chemotherapies in NSCLC in the meta-analysis. For the XPG C46T polymorphisms, a significant association with an objective response was detected. Multiple and large-scale studies are required to further investigate the association between biomarkers and tumor prognosis.

The effect of XPD polymorphisms on digestive tract cancers risk: a meta-analysis.

BackgroundThe Xeroderma pigmento-sum group D gene (XPD) plays a key role in nucleotide excision repair. Single nucleotide polymorphisms (SNP) located in its functional region may alter DNA repair capacity phenotype and cancer risk. Many studies have demonstrated that XPD polymorphisms are significantly associated with digestive tract cancers risk, but the results are inconsistent. We conducted a comprehensive meta-analysis to assess the association between XPD Lys751Gln polymorphism and digestive tract cancers risk. The digestive tract cancers that our study referred to, includes oral cancer, esophageal cancer, gastric cancer and colorectal cancer.MethodsWe searched PubMed and EmBase up to December 31, 2012 to identify eligible studies. A total of 37 case-control studies including 9027 cases and 16072 controls were involved in this meta-analysis. Statistical analyses were performed with Stata software (version 11.0, USA). Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association.ResultsThe results showed that XPD Lys751Gln polymorphism was associated with the increased risk of digestive tract cancers (homozygote comparison (GlnGln vs. LysLys): OR = 1.12, 95% CI = 1.01–1.24, P = 0.029, P heterogeneity = 0.133). We found no statistical evidence for a significantly increased digestive tract cancers risk in the other genetic models. In the subgroup analysis, we also found the homozygote comparison increased the susceptibility of Asian population (OR = 1.28, 95% CI = 1.01–1.63, P = 0.045, P heterogeneity = 0.287). Stratified by cancer type and source of control, no significantly increased cancer risk was found in these subgroups. Additionally, risk estimates from hospital-based studies and esophageal studies were heterogeneous.ConclusionsOur meta-analysis suggested that the XPD 751Gln/Gln genotype was a low-penetrate risk factor for developing digestive tract cancers, especially in Asian populations.