XRCC1 Arg194Trp Polymorphisms Research Articles

Interactive Association of XRCC1, XRCC2, XRCC3, and TP53 Gene Polymorphisms With Gastrointestinal Cancer Risk: Insights From a Hospital-Based Case-Control Study.

Gastrointestinal (GI) cancer presents a significant worldwide health burden, influenced by a combination of genetic and environmental factors. This study endeavors to explore the combined effects of the XRCC1, XRCC2, XRCC3, and TP53 genes that contribute to the heightened risk of GI cancer, shedding light on their combined influence on cancer susceptibility. A total of 200 histologically confirmed cases of GI cancerand an equal number of controlswere selected to examine genetic polymorphisms within the XRCC1, XRCC2, XRCC3, and TP53 genes using the polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP). Odds ratios (OR) with 95% confidence intervals (CI) were calculated to assess the association of these polymorphisms with GI cancer susceptibility, with statistical significance (p ≤ 0.05). Logistic regression analysis confirmed strong evidence of synergistic interactions among specific variant genotypes. Notably, combinations such as heterozygous Arg/Ser+Ser/Ser genotype of TP53 Arg249Ser polymorphism with Arg/Trp+Trp/Trp genotype of XRCC1 Arg194Trp polymorphism (OR=2.64; 95% CI: 1.35-5.18; p=0.004),Arg/Gln+Gln/Gln genotype of XRCC1 at codon 399 (OR=5.04; 95% CI: 2.81-9.05; p=0.0001), Arg/His and His/His genotypes of XRCC2 Arg188His (OR=2.16; 95% CI: 1.06-4.39; p<0.032), and Thr/Met+Met/Met genotype of XRCC3 Thr242Met (OR=3.48; 95% CI: 1.79-6.77; p=0.0002) showed significant associations with GI cancer risk in the study population. The findings indicate a notable association between the combined effect of heterozygous variant genotypes of TP53 and variant genotypes of XRCC1, XRCC2, and XRCC3 on GI cancer risk. However, further research with a larger sample size and broad single nucleotide polymorphism (SNP) spectra is necessary to understand the interaction between genetic variations and environmental factors influencing GI cancer susceptibility.

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&amp;lt;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&amp;gt;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.

Gene polymorphisms and prognosis of head and neck squamous cell carcinoma: a systematic review.

Head and neck squamous cell carcinomas (HNSCCs) are associated with variable prognosis even with similar clinical characteristics and treatments. Gene polymorphisms have been suggested as prognostic factors for HNSCC which can justified this variable prognosis. So, the aim was to review literatures on gene polymorphisms and prognosis of HNSCCs. A systematic search was conducted using PubMed, Web of science, SCOPUS, Google Scholar and Cochrane library databases to find all related articles published up to December 2021 in the field of gene polymorphisms and HNSCC prognosis. Of 1029 initial searched articles, 71 articles were selected for inclusion in this systematic review. About 93 genes and 204 polymorphisms have been discussed in these articles. Among the most studied polymorphisms, the XRCC1 Arg399Gln and Arg194Trp polymorphisms were not associated with survival in most studies; the ERCC1 C19007T polymorphism had no significant association in any of the studies. Different gene polymorphisms of glutathione s-transferase family, including GSTM1 deletion, GSTT1 deletion and GSTP1 A313G, were not associated with survival in included studies. There are conflicting results regarding the association between polymorphisms such as ERCC2 A35931C, Asp312Asn, ERCC5 rs1047768 and rs17655 with HNSCC prognosis. Less studied polymorphisms, such as hOGG1 rs1052133 or the VEGF rs699947, were generally not associated with HNSCC prognosis. Reviewed articles reported varied and contradictory results regarding the association of gene polymorphisms and HNSCC prognosis, which necessitates further studies along with meta-analysis on the results of such studies.

A Meta-Analysis for Association of XRCC1, XRCC2 and XRCC3 Polymorphisms with Susceptibility to Thyroid Cancer.

Background:We conducted a comprehensive meta-analysis to explore the association of polymorphisms at XRCC1, XRCC2 and XRCC3 genes with susceptibility to thyroid cancer (TC). Methods:We searched PubMed, EMBASE, Web of Science, and CNKI for relevant available studies. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the strength of the associations. Results:A total of 67 studies including 17 studies with 6,806 cases and 5,229 controls on XRCC1 Arg399Gln, 13 studies with 3,234 cases and 4,807 controls on XRCC1 Arg280His, 13 studies with 2,956 cases and 3,860 controls on XRCC1 Arg194Trp, five studies with 1,287 cases and 1,422 controls on XRCC2 Arg188His, 13 studies with 2,488 cases and 3,586 controls on XRCC3 Thr241Met, and six studies with 1,828 cases and 2,060 controls on XRCC3 IVS5-14 polymorphism were selected. Polled data revealed that the XRCC1 Arg399Gln, Arg280His, Arg194Trp, XRCC2 Arg188His and XRCC3 Thr241Met and IVS5-14 polymorphisms were not significantly associated with an increased risk of TC. Stratified analyses by ethnicity showed that the XRCC1 Arg399Gln polymorphism was associated with TC risk in Caucasians, but not in Asians. Conclusions:Our meta-analysis indicated that the XRCC1 Arg399Gln, Arg280His, Arg194Trp, XRCC2 Arg188His, XRCC3 Thr241Met and IVS5-14 polymorphisms were not associated with risk of TC in the global population. Further well-designed investigations with large sample sizes are required to confirm our results.

Genetic polymorphisms of base excision repair gene XRCC1 and susceptibility to benzene among employees of chemical industries

Benzene is the most dangerous combination of volatile organic compounds (VOCs) due to its carcinogenicity and toxic effects on the blood system. Benzene toxicity is rooted in its metabolism. This material can break the DNA and cause some changes in the base sequence. The XRCC1 gene plays an important role in repairing the damaged base since the polymorphisms of gene XRCC1 (rs1799782) and (rs25487), which lead to an increased risk of various cancers, are common. In this study, the association between the mentioned polymorphisms and the risk of individuals' vulnerability to benzene was investigated in a group of people exposed to benzene in an Iranian context. One hundred thirty-eight subjects suffering from blood disorders (case group) and 168 subjects without any blood disorder (control group) were evaluated. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used for XRCC1 Arg194Trp and XRCC1 Arg399Gln polymorphism detection. The results showed that XRCC1 Arg194Trp and Arg399Gln polymorphisms had no significant association with susceptibility to benzene. Similarly, Arg399Gln and Arg194Trp genotypes did not have any significant relationship with hematological parameters. The obtained results indicated that the distribution of genotypes was in Hardy-Weinberg equilibrium in both groups. Different geographic locations, population size, and different genetic backgrounds might probably have affected the results.

XRCC1 Arg194Trp polymorphism and thyroid cancer.

Previously published data on the association between the XRCC1 Arg194Trp polymorphism and thyroid cancer (TC) remain controversial. To clarify the association between the XRCC1 Arg194Trp polymorphism and susceptibility to TC, a meta-analysis of case-control studies was conducted. We systematically searched PubMed and CNKI to identify relevant studies. Pooled odds ratios (ORs) of various genetic models were estimated using fixed and random effects models. Heterogeneity was detected by Q-statistic, and the Egger's test was used to evaluate the publication bias. A total of seven eligible studies for the XRCC1 Arg194Trp polymorphism (1500 patients and 2358 controls) were included in this meta-analysis. The results of our study failed to suggest an association between the Arg194Trp polymorphism and susceptibility of TC. However, in the subgroup analyses by ethnicity, the OR was 0.82 (C allele vs. T allele, 95% CI 0.68-0.98; P = 0.24 for heterogeneity) among the Chinese population. Nevertheless, no significant differences were observed in the Caucasian population in any genetic model. This study suggested that the C allele of XRCC1 had an 18% significantly decreased risk of TC in Chinese, and there were no significant associations among Caucasians under all genetic models.

The influence of polymorphisms of xenobiotic-metabolizing and DNA repair genes in DNA damage, telomere length and global DNA methylation evaluated in open-cast coal mining workers.

Coal plants represent one of the main sources of environmental pollution due to the combustion process of this mineral and the consequent release of gases and particles which, in significant quantities, can lead to a potential risk to health and the environment. The susceptibility of individuals to the genotoxic effects of coal mining can be modulated by genetic variations in the xenobiotic detoxification and DNA repair processes. The aim of this study was to evaluate if xenobiotic metabolism polymorphism, base excision repair polymorphisms and non-homologous end joining repair polymorphism, could modify individual susceptibility to genomic instability and epigenetic alterations induced in workers by occupational exposure to coal. In this study, polymerase chain reaction was used to examine the polymorphic sites. The sample population comprising 70 coal mine workers and 71 workers non-exposed to coal. Our results demonstrated the effect of individual genotypes on different biomarkers evaluated. Significant decrease in % of global DNA methylation were observed in CYP1A1 Val/- exposed individuals compared to CYP1A1 Ile/Ile individuals. Coal workers who carried the XRCC4 Ile/Ile genotype showed decrease NBUD frequencies, while the XRCC4 Thr/- genotype was associated with decrease in Buccal micronucleus cells for the group not exposed. No influence of GSTM1 null, GSTT1 null, GSTP1 Ile105Val, hOGG1 Ser326Cys, XRCC1 Arg194Trp polymorphisms was observed. Thus, the current study reinforces the importance of considering the effect of metabolizing and repair variant genotypes on the individual susceptibility to incorporate DNA damage, as these processes act in a coordinated manner to determine the final response to coal exposure.

Association of XRCC1, HMMR genes with breast cancer in the Kyrgyz ethnic group

An association of genes XRCC1 and HMMR with breast cancer (BC) has never been tested in the Kyrgyz ethnic group. This was a case-control study of 201 women of the Kyrgyz ethnic group with a morphologically verified breast cancer (N=99) and 102 controls age-matched with BC cases. The mean age of the patients was 53 years (24–74, SE mean = 0.967, STD=9.81). The extraction of DNA was carried out from venous blood. The genotyping was conducted by using the method of polymerase chain reaction and restriction fragment length polymorphism. When comparing the results of genotyping, the histological structure of the tumor and the «menopause» factor, Fisher»s exact test was used. Calculation of the odds ratio was carried out by cross tabulation method. A statistically significant link between the XRCC1 Arg194Trp polymorphism and the menopausal status was observed (p=0,018). The Arg / Arg genotype of XRCC1 Arg194Trp polymorphism occurred in 52 % of cases in women at menopausal age, whereas in women before the onset of menopause, the genotype Arg / Arg occurred in 78.8 % of BC cases (p=0.009). The CT genotype of HMMR V353A polymorphism was identified as “protective” factor – OR=0.481, 95 % CI [0.27‑0.85]. There was no statistically significant association between the results of genotyping and histological structure of the tumor, as well as the age of verification of the diagnosis of BC.

XRCC1 variants do not represent a risk for dermatomyositis and systemic lupus erythematosus in Bulgarian patients

Systemic lupus erythematosus (SLE) and dermatomyositis (DM) share a similar pathogenesis, and genetic, hormonal, and environmental factors are known to trigger the autoimmune process. The X-ray repair cross-complementing genes (XRCC1 and XRCC3) are known to play a central role in mammalian DNA repair processes. Evidence suggests that impaired DNA repair efficiency is implicated in the development of autoimmune diseases. This case-control study investigates the association between the XRCC1 Arg194Trp (C>T) and Arg399Gln (G>A) polymorphisms and the susceptibility to DM and SLE in Bulgarian patients. Altogether 88 patients, 55 with SLE and 33 with DM, and 94 unrelated healthy controls were included in this study. None of the polymorphisms showed an association with SLE, DM, or their clinical parameters. The allele and genotype frequency of the two single nucleotide polymorphisms was similar to those found in other healthy Caucasian populations. Our results indicate that the XRCC1 rs1799782 Arg194Trp and rs25487 Arg399Gln polymorphisms do not play a role in the susceptibility to SLE and DM.

Polymorphisms of base-excision repair genes and the hepatocarcinogenesis

AimTo determine the possible association between polymorphisms of DNA repair genes, including XRCC1 Arg194Tryp, Arg280His, and Arg399Glu, APE1 Asp148Glu, and NEIL2 Arg257Leu, and the risk of developing hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC). MethodsA total of 264 subjects were recruited in this retrospective case-control study and were categorized into four groups: 88 control subjects (CR), 53 chronic hepatitis C patients (CHC), 36 liver cirrhotic patients (LC), and 87 HCC patients. The XRCC1 Arg194Tryp, Arg280His, and Arg399Glu polymorphisms were detected using PCR-RFLP, while real-time PCR was used to genotype APE1 Asp148Glu and NEIL2 Arg257Leu. ResultsOur data revealed that, compared with the healthy controls, for those subjects with the XRCC1 Arg194Trp genotype, the risk of developing CHC, LC, and HCC was increased by 6.66- (odds ratio (OR) = 6.667; 95% confidence interval (CI) = 3.244–13.701; P > 0.01), 3.85- (OR = 3.852; 95% CI = 1.797–8.256; P > 0.01), and 2.14-fold (OR = 2.14; 95% CI = 1.13–4.06; P > 0.05), respectively. There was no association between the risk of HCC development and the XRCC1 Arg280His or XRCC1 Arg399Gln genotypes. Moreover, the analysis showed a lack of association between APE1 Asp148Glu and the risk of HCC development. The analysis of clinicopathological parameters showed that the HCC patients with the XRCC1 Arg280His polymorphism were 2.9 fold more likely to have hepatic lesions in both hepatic lobes (OR: 2.9; 95% CI: 1.15–7.29). Notably, in the HCC patients, the prevalence of the APE1 polymorphism in the males was four times higher than that in the females (OR = 4; 95% CI = 1.129–14.175; P > 0.05). ConclusionOur results indicate that the XRCC1 Arg194Trp polymorphism could be a risk factor for HCV-related HCC development in Egypt.

Base excision repair (OGG1 and XRCC1) and metabolism (PON1) gene polymorphisms act on modulation of DNA damage and immune parameters in tobacco farmers

Pesticides are one of the most frequently investigated chemical, due to their multiple uses in agricultural and public health areas. This study evaluates lymphocytes CBMN (cytokinesis-block micronucleus cytome assay), inflammatory markers, inorganic elements in blood samples, and the relationship of these parameters with XRCC1Arg194Trp, OGG1Ser326Cys and PON1Gln192Arg polymorphisms in a population of tobacco farmers. The study population comprised 129 agricultural workers exposed to pesticides and 91 nonexposed. Farmers had significantly increased NPB (nuclear plasmatic bridge), MN (micronucleus) and NBUD (nuclear bud) frequencies, as well as IL-6 (interleukin 6) and TNF-α (tumor necrosis factor alpha) serum levels, and decreased cytokines CD4+/CD8+ ratio. In the exposed group, XRCC1 Trp/- was correlated with decreased NDI (nuclear division index), and OGG1 Cys/- was associated with higher levels of NPB and decreased levels of IL-6. The combined effects of PON1 Arg/- and XRCC1 Arg/Arg were associated with increased NPB frequencies. In addition, the combination of PON1 Arg/- with XRCC1 Trp/- or OGG1 Cys/- influenced in increased levels of necrosis in farmers. Furthermore, tobacco farmers showed a positive correlation between TNF-α levels and NPB, CD4+/CD8+ ratio and NBUD; and IL-6 levels with both MN and NDI. The duration of years of work at tobacco fields was correlated positively with NBUD frequency. Sulfur, chlorine and potassium were found at increased levels in the exposed group when compared to the nonexposed one. These findings provide evidence that tobacco farmers’ exposure have increased DNA damage and alter the immune system’s response, and that XRCC1 and OGG1 polymorphisms could influence both biomarkers results.

Association of the XRCC1 Arg194Trp and Arg399Gln polymorphisms with depression and hopelessness levels in individuals exposed to sour gas

Some parts of Masjid-i-Sulaiman (MIS; southwest of Iran) are polluted by natural sour gas. Previously it has been shown that among MIS citizens the incidence of suicide attempts and self-burning and the frequency of depression and hopelessness are remarkably high. In order to investigate the association of the XRCC1 genetic polymorphisms (at codons 194 and 399) with depression and hopelessness levels of participants exposed to sour gas, the present cross-sectional study was carried out on 206 healthy persons living in the contaminated areas of MIS. The genotypes of XRCC1 were determined using PCR based method. Depression and hopelessness scores were determined using Beck's depression inventory and Beck's hopelessness scale, respectively. The “Arg/Trp + Trp/Trp” genotypes of Arg194Trp polymorphism were positively correlated with hopelessness and depression levels. However there was no statistical association between the genotypes of Arg399Gln polymorphism and the hopelessness and depression levels. Our data indicated that the Trp194-Arg399 haplotype was significantly associated with the higher hopelessness (OR = 3.95, 95% CI = 1.34–11.5, P = 0.012) and depression levels (OR = 2.55, 95% CI = 1.15–5.66, P = 0.021). The Trp194 vs Arg194 allele (OR = 4.49, 95% CI = 1.33–15.1, P = 0.008) and the Trp194-Arg399 vs Arg194-Arg399 haplotype (OR = 4.66, 95% CI = 1.35–16.1, P = 0.015) significantly increased in “hopeless and depressed persons” compared with the “without hopelessness and depression” group. The impact of polymorphisms on the function of XRCC1 deserve more attention and also further studies are required to conclude clinical diagnosis of depressive disorders in polluted areas of MIS and study the adverse effects of H2S on brain function.

Impact of CYP1A1, GSTP1 and XRCC1 genes polymorphisms on toxicity and response to chemotherapy in childhood acute lymphoblastic leukemia

BackgroundAcute lymphoblastic leukemia (ALL) is the most common childhood malignancy. The interindividual genetic variations in drug metabolizing enzymes and DNA repair genes influence the efficacy and toxicity of numerous chemotherapeutic drugs affecting the treatment outcome. Aim of the workThe aim of the study was to investigate the impact of drug metabolizing CYP1, GSTP1 and DNA repair (XRCC1) genes polymorphisms on the toxicity and response to chemotherapy in childhood ALL. Patients and methodologyNinety seven ALL pediatric patients were genotyped for CYP1A1, GSTP1 ILe105Val and XRCC1 Arg194Tryp single nucleotide polymorphisms (SNPs) using PCR-RFLP. ResultsNo statistically significant differences were observed between the wild and variant (homozygous and heterozygous) genotypes of the polymorphisms studied in CYP1A1, GSTP1 or XRCC1 genes regarding age, total leukocyte count, immunophenotyping, cytogenetic or risk group. The SNPs in CYP1A1, GSTP1 and XRCC1 genes did not show significant association with complete remission (CR) rate, overall survival (OS) or event free survival (EFS). However, XRCC1 Arg194Trp SNP was associated with higher drug toxicity; carriers of variant genotypes (CT and TT) had a significantly higher frequency of myelosuppression compared to those with the wild CC genotype (21/43[48.8%]) compared to (14/54[25.9%]) (p=0.020). The analysis of the combined effect of studied SNPs did not show any significant association with patient outcome. ConclusionOur study reported a significant association between the DNA repair gene polymorphism and myelosuppression in childhood ALL patients. Adjustment of the dose of chemotherapeutic agents according to XRCC1 Arg194Trp polymorphism may improve outcome in cases with risk of toxicity.

Investigation of XRCC1 Arg399Gln, Arg280His, and Arg194Trp polymorphisms effects on the induction of micronucleus by Aflatoxin B1 in in vitro

Aflatoxin B1 (AFB1) is a genotoxic mycotoxin that can contaminate a wide variety of foods. The aim of this study was to examine the associations between XRCC1 Arg399Gln, Arg280His, and Arg184Trp polymorphisms and the frequencies of spontaneous and AFB1-induced DNA damage in peripheral blood lymphocytes from 100 healthy individuals in Turkish population. In vitro cytokinesis-blocked micronucleus (CMBN) assay was used to detect the spontaneous and AFB1-induced DNA damage. Genotyping of XRCC1 Arg399Gln, Arg280His, and Arg194Trp polymorphisms were carried out by using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) assay. Treatment of the lymphocytes with AFB1 slightly increased (for Arg399Gln 0.73±0.4 vs. 0.40±0.26, Arg280His 0.80±0.4 vs. 0.41±0.28) the overall frequencies of micronucleus (MN) when compared to untreated cultures. No results were obtained for Arg194Trp polymorphism. Obtained overall results do not correspond to any significant (P<0.05) association between XRCC1 Arg399Gln, Arg280His, and Arg194Trp Polymorphisms and MN frequencies. The results of this study indicate that Arg399Gln, Arg280His, and Arg194Trp polymorphisms do not play an important role in human sensitivity to the genotoxic effects of AFB1.

Reappraisal of XRCC1 Arg194Trp polymorphism and glioma risk: a cumulative meta-analysis.

The association between XRCC1 Arg194Trp polymorphism and glioma risk were inconsistent from published meta-analyses and epidemiological studies. Hence, we performed this updated and cumulative meta-analysis to reappraisal this relationship. PubMed, Embase, CBM (Chinese Biomedical Database), and CNKI (China National Knowledge Internet) databases were comprehensively searched up to August 13, 2016 (updated on December 22, 2016). After study selection and data extraction from eligible studies, the association was evaluated by odds ratios (ORs) and its 95% confidence intervals (95%CIs) using Comprehensive Meta-Analysis software. Finally 16 case-control studies involving 7011 patients and 9519 healthy controls were yielded. The results indicated that XRCC1 Arg194Trp polymorphism was significantly correlated with the increased risk of glioma [Trp vs. Arg: OR = 1.18(1.05-1.34); TrpTrp vs. ArgArg: OR = 1.66(1.31-2.12); ArgTrp vs. ArgArg: OR = 1.34(1.02-1.77); TrpTrp vs. ArgArg+ArgTrp: OR = 1.47(1.26-1.72); TrpTrp+ArgTrp vs. ArgArg: OR = 1.17(1.01-1.35)]. Cumulative analysis showed the results changed from non-significant to significant when new studies accumulated, and sensitivity analysis indicated the results were stable. Subgroup analysis showed the significant association existed in Asians but not in Caucasians. Current evidence indicated that XRCC1 Arg194Trp polymorphism was associated with increased risk for glioma, especially in Asians; however, relevant studies involving other ethnic groups are required to validate our findings in further.

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.

Quantitative assessment of the association between XRCC1 Arg399Gln and Arg194Trp polymorphisms and risk of cutaneous melanoma.

Accumulating evidence has suggested that the XRCC1 Arg399Gln and Arg194Trp polymorphisms might be related to cutaneous melanoma susceptibility. However, epidemiologic findings have been inconsistent. We have assessed reported studies by meta-analysis to perform a more precise estimation of the association between the XRCC1 two polymorphisms (Arg399Gln, Arg194Trp) and risk of cutaneous melanoma. A total of seven eligible articles were selected for this meta-analysis, including 3454 cases and 3811 controls for the XRCC1 Arg399Gln polymorphism and 1256 cases and 1575 controls for the XRCC1 Arg194Trp polymorphism. Overall, no significant associations were found in all genetic models when the studies were pooled into the meta-analysis for the Arg399Gln and Arg194Trp polymorphisms. When stratified by source of control, significant associations were found for the Arg399Gln polymorphism in the population-based subgroup under AA versus GG [odds ratio (OR)=1.43, 95% confidence interval (CI)=1.08-1.88]; the dominant model AA/GA versus GG (OR=1.25, 95% CI=1.04-1.51); and the recessive model AA versus GA/GG (OR=1.31, 95% CI=1.01-1.68). No significant associations were found for the Arg194Trp polymorphism in the subgroup analysis. This meta-analysis suggested that the XRCC1 Arg399Gln polymorphism was a risk factor for cutaneous melanoma in population-based subgroup.

Analysis of XRCC1 Arg194Trp polymorphism and the risk of idiopathic male infertility

Analysis of XRCC1 Arg194Trp polymorphism and the risk of idiopathic male infertility

English

Abstract Coroner artery disease, the leading cause of morbidity and mortality worldwide, is an inflammatory disease. XRCC1 gene is playing the role of scaffolding protein for the base excision repair (BER) and single strand break (SSB) repair. The study population consisted of 402 participants living in the same region, classified into case group (n=201) and control group (n=201). Phenol-chloroform method was used to extract DNA from blood samples of the study participants. XRCC1 genotypes were determined using PCR/RFLP methods. No statistically significant difference was found between the study groups in terms of allele and genotype frequencies in XRCC1 Arg194Trp polymorphism. However, distribution of XRCC1 399Gln allele frequency was found to differ at a statistically significant level between the case and control groups (p=0.003; OR=1.56). Regarding the Arg/Arg genotype in Arg399Gln polymorphism, a statistically significant difference was detected in the distribution of Gln/Gln genotype (p=0.017; adj OR=3.11). Statistically significant differences were also recorded for Arg399Gln polymorphism among the smoking male participants with hypertension (p=0.009; p=0.031; p=0.032, respectively). The study suggests that XRCC1 399Gln/Gln genotype may be a significant risk factor for coronary artery disease.

Association of DNA repair and xenobiotic pathway gene polymorphisms with genetic susceptibility to gastric cancer patients in West Bengal, India.

Gastric cancer is one of the most common malignancies in India. DNA repair gene or xenobiotic pathway gene polymorphisms have recently been shown to affect individual susceptibility to gastric cancer. Here, the possible interaction between common polymorphisms in X-ray repair cross complementing group I (XRCC1) gene and glutathione S-transferase (GST) genes (GSTM1, GSTT1 and GSTP1), smoking and alcohol consumption and overall survival in gastric cancer patients were evaluated. In this population-based case control study, 70 gastric cancer patients and 82 healthy controls were enrolled. The epidemiological data were collected by a standard questionnaire, and blood samples were collected from each individual. XRCC1 Arg194Trp, Arg280His and Arg399Gln polymorphisms were determined by polymerase chain reaction and direct DNA sequencing. GSTM1 and GSTT1 null polymorphisms and GSTP1 Ile105Val polymorphism were identified by multiplex polymerase chain reaction and restriction fragment length polymorphism (RFLP), respectively. The risk of gastric cancer was significantly elevated in individuals with XRCC1 Arg/Gln +Gln/Gln (p = 0.031; odds ratio = 2.32; 95% confidence interval (CI) 1.07-5.06) and GSTP1 Val/Val genotype (p = 0.009; odds ratio = 8.64; 95% CI 1.84-40.55). An elevated risk for GC was observed in smokers and alcohol consumers carrying GSTP1 Ile/Val +Val/Val genotype (p = 0.041; odds ratio = 3.71; 95% CI 0.98-14.12; p = 0.002; odds ratio = 12.31; 95% CI 1.71-88.59). These findings suggest that XRCC1 rs25487 and GSTP1 rs1695 can be considered as a risk factor associated with gastric cancer and might be used as a molecular marker for evaluating the susceptibility of the disease.