X-ray Repair Cross-complementing Group 1 Gene Polymorphisms Research Articles

The XRCC1 and TP53 gene polymorphisms are associated with advanced-stage disease and early distant metastasis at diagnosis in non-small cell lung cancer.

Studies on single nucleotide polymorphisms (SNPs) in non-small cell lung cancer (NSCLC) suggest that DNA repair capacity may have prognostic implications for disease recurrence and survival. However, there is no study investigating the relationship between SNPs and the risk of metastasis at the time of initial diagnosis in patients with NSCLC. This study aimed to investigate the potential predictive value of SNPs in detecting the risk of metastasis at the time of initial diagnosis and poor prognosis in patients with NSCLC. In this prospective cohort study, we evaluated 275 patients with NSCLC. Analysis of SNPs from peripheral blood cells was performed by a polymerase chain reaction. Excision repair cross-complementing group 1 (ERCC1)- Asn118Asn, excision repair cross-complementing group 2 (ERCC2)-Lys751Gln, X-ray repair cross-complementing group 1 (XRCC1)-Arg399Gln, and tumor protein 53 (TP53)-Arg72Pro polymorphisms were evaluated in conjunction with the development of metastasis. The ERCC1 normal genotype, ERCC2 heterozygote genotype, XRCC1 normal genotype, and TP53 normal genotype were associated with a higher stage and more advanced-stage disease at the time of initial diagnosis (P = 0.027, 0.005, <0.001, and 0.006, respectively). Also, XRCC1 normal genotype and TP53 normal genotype were associated with the risk of metastasis at the time of initial diagnosis (P = <0.001 and 0.002, respectively). Moreover, the XRCC1 normal genotype was associated with the risk of brain metastasis at the time of initial diagnosis (P = 0.031). We showed that SNPs are related to a higher stage and more advanced-stage disease at the time of initial diagnosis in patients with NSCLC, and XRCC1 and TP53 gene polymorphisms are associated with the risk of metastasis. These results may contribute to the identification of high-risk groups and may help to earlier diagnosis and treatment in patients with NSCLC.

The Possible Role of XRCC1 Gene Polymorphisms with Idiopathic Non-obstructive Azoospermia in Southeast Turkey.

X-ray repair cross-complementing group 1 (XRCC1) plays a role in repairing DNA damage during spermatogenesis. We examined the effects the possible role of two single nucleotide polymorphisms of XRCC1 Arg194Trp and Arg399Gln in DNA repair gene XRCC1 with risk of idiopathic non-obstructive azoospermia (INOA) in a south-east Turkey population. The genotype and allele frequencies of two observed polymorphisms of XRCC1 Arg194Trp and Arg399Gln were examined by polymerase chain reaction-restriction fragment length polymorphism in 102 infertile men with INOA and 102 fertile controls. In our study, all the observed genotype frequencies are in agreement with Hardy-Weinberg equilibrium. The genotype frequencies of the XRCC Arg194Trp were 84% (CC), 16% (CT) and 2% (TT) among the men with INOA, while the frequencies of those genotypes in the controls were found to be 88% (CC), 12% (CT) and 2% (TT) (?2 test: P < .05). Similarly, the genotypes frequencies of GG, GA, and AA of the XRCC1 Arg399Gln were 44%, 39%, and 19% in the group of men with INOA, whereas these frequencies were 42%, 45%, and 15% in the control group, respectively. No significant difference between the control group and the men with INOA were found in the frequencies of genotypes and allele of XRCC1 Arg194Trp and Arg399Gln (P > 0.05). Neither Arg194Trp nor Arg399Gln polymorphisms in the XRCC1 gene influenced risk of INOA in our study. However, these findings may be helpful in improving the understanding of the etiology of male infertility.

Gene polymorphism of DNA repair gene X-ray repair cross complementing group 1 and xeroderma pigmentosum group D and environment interaction in non-small-cell lung cancer for Chinese nonsmoking female patients.

An association between genetic polymorphisms in encoding X-ray repair cross complementing group 1 (XRCC1) and encoding xeroderma pigmentosum group D (XPD) and risks of non-small-cell lung cancer (NSCLC) in East Chinese Han population has been observed. Herein we hypothesized that genetic polymorphisms in these two DNA repair genes are likely to be important in the NSCLC in Chinese nonsmoking female patients. We recruited 327 nonsmoking female patients with NSCLC and 342 individuals with benign lung diseases or healthy controls. Genotype frequencies of XRCC1 T-77C, Arg194Trp, Arg280His and Arg399Gln, Pro206Pro, and XPD Asp312Asn and Lys751Gln were calculated after Polymerase Chain Reaction amplification and sequencing. Generalized multifactor dimensionality reduction (GMDR) was used to detect the interactive effect of XRCC1 and XPD gene polymorphisms. The ratio of cooking oil mist exposure history and soot exposure history, and the gene frequencies of XRCC1 T-77C TC + CC, XRCC1 AG + GG, XRCC1 399Gln/Gln, and XPD 751Gln/Gln were higher in female patients with NSCLC than those with benign lung diseases or healthy controls. The haplotypes of XRCC1 T-Arg-Arg-Gln and XRCC1 C-Arg-Arg-Arg were positively associated with the NSCLC occurrence in nonsmoking female patients. GMDR discovered that there was an interactive model of XRCC1 and XPD genes in multiple gene loci. Logistic regression analysis showed that XRCC1 T-77C, XRCC1 Pro206Pro polymorphism, cooking oil mist and soot exposure history and tumor-node-metastasis (TNM) stage were related to NSCLC occurrence for nonsmoking female patients. Taken together, XRCC1 and XPD polymorphisms, cooking oil mist, and soot exposure history may be interactively correlated with NSCLC incidence for nonsmoking female patients.

The X-ray Repair Cross-Complementing Group 1 Arg399Gln Genetic Polymorphism and Risk of Hepatocellular Carcinoma in an Iranian Population.

BACKGROUND The association between X-ray repair cross-complementing group 1 (XRCC1) Arg399Gln gene polymorphism and hepatocellular carcinoma (HCC) has been investigated in several populations. However, the findings are controversial. The aim of this study was to address the association between XRCC1 Arg399Gln polymorphism and HCC in an Iranian population. METHODS We have evaluated the association between XRCC1 Arg399Gln gene polymorphism and HCC in 151 Iranian individuals (50 patients with HCC and 101 healthy matched controls) using polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) method. RESULTS Significant association was found for the XRCC1 A allele and HCC [OR = 1.93, 95% CI (1.16 - 3.25), P = 0.0099]. Also, genotype analysis by SNPStats online software showed a significant association between XRCC1 gene polymorphisms and HCC under co-dominant, dominant, and recessive genetic models. CONCLUSION Our study provides evidence that the XRCC1 Arg399Gln polymorphism may be associated with the risk of HCC development in Iranian population.

Association between Polymorphisms of X-Ray Repair Cross Complementing Group 1 Gene and Pancreatic Cancer Risk: a Systematic Review with Meta-Analysis

Emerging evidences have shown that common genetic polymorphisms in X-ray repair cross complementing group 1 (XRCC1) gene may be associated with the development of pancreatic cancer, but individually published studies and previous meta-analyses revealed inconclusive results. The aim of our study was to investigate the association between polymorphisms in XRCC1 gene and pancreatic cancer risk. We conducted a search of PubMed, Embase, the Cochrane Library and Web of Science databases. Odds ratios (ORs) with 95% confidence intervals (CIs) were determined as measures of the strength of association between polymorphisms of XRCC1 and pancreatic cancer risk. Sensitivity analysis and publication bias were evaluated. All analyses were undertaken using the STATA 13.0. A total of 10 studies were included in this systematic review. Five common functional single-nucleotide polymorphisms (SNPs) in XRCC1 gene were found, including Arg399Gln G > A (rs25487), Arg194Trp C > T (rs1799782), Arg280His G > A (rs25489), c.1517G > C, c.1471G > A. Results from our stratified analysis based on Hardy-Weinberg equilibrium (HWE) showed that there was a robust significant association between Arg280His polymorphism and pancreatic cancer risk (allelic model, OR 0.743, 95% CI 0.576–0.958, P = 0.022; heterozygous model, OR 0.701, 95% CI 0.525–0.936, P = 0.016; dominant model, OR 0.710, 95% CI 0.537–0.939, P = 0.016). We also found a statistically significant association between c.1517G > C polymorphism and pancreatic cancer risk (Allelic model, OR 1.252, 95% CI 1.064–1.473, P = 0.007). No significant results were obtained for Arg399Gln, Arg194Trp and c.1471G > A polymorphisms. The present meta-analysis suggested that Arg280His and c.1517G > C polymorphisms in XRCC1 gene were associated with pancreatic cancer risk.

Lack of correlation between X-ray repair cross-complementing group 1 gene polymorphisms and the susceptibility to colorectal cancer in a Malaysian cohort.

X-ray repair cross-complementing group 1 (XRCC1) is one of the key components in the base excision repair pathway that repairs erroneous DNA lesions and removes nonbulky base adducts for the maintenance of genome integrity. Studies have revealed that differences in individual DNA repair capacity can impact the interindividual variation in cancer susceptibility, tumour aggressiveness and treatment response. The relationship between XRCC1 and sporadic colorectal cancer (CRC) susceptibility, which is hitherto inconclusive, has been explored in many association studies of different populations. In view of the conflicting findings generated, we aimed to investigate the association between XRCC1 and genetic predisposition to CRC among Malaysians. The present case-control association study was conducted on 130 CRC patients and 212 age-matched healthy controls. The genotyping of XRCC1 Arg194Trp, Arg280His and Arg399Gln single nucleotide polymorphisms was performed with allele-specific real-time PCR approach. This was followed by basic statistical analysis on the single nucleotide polymorphisms and haplotype data obtained. No significant difference in the allele and genotype frequencies was observed between CRC patients and healthy controls (P>0.05). There was also no association observed between XRCC1 haplotypes and CRC (P>0.05). In conclusion, a positive association between XRCC1 gene polymorphisms and CRC risk was not established in our Malaysian population.

The XRCC 1 DNA repair gene modifies the environmental risk of stomach cancer: a hospital-based matched case-control study

BackgroundPrevious studies have found that polymorphisms of the DNA repair gene X-ray repair cross-complementing group 1(XRCC1) and environmental factors are both associated with an increased risk of stomach cancer, but no study has reported on the potential additive effect of these factors among Thai people. The aim of this study was to investigate whether the risk of stomach cancer from XRCC1 gene polymorphisms was modified by environmental factors in the Thai population.MethodsHospital-based matched case-control study data were collected from 101 new stomach cancer cases and 202 controls, which were recruited from2002 to 2006 and were matched for gender and age. Genotype analysis was performed using real-time PCR-HRM. The data were analysed by the chi-square test and conditional logistic regression.ResultsThe Arg/Arg homozygote polymorphism of the XRCC1 gene was associated with an increased risk of stomach cancer in the Thai population (OR adj, 3.7; 95%CI, 1.30–10.72) compared with Gln/Gln homozygosity. The effect of the XRCC1gene on the risk of stomach cancer was modified by both a high intake of vegetable oils and salt (p = 0.036 and p = 0.014), particularly for the Arg/Arg homozygous genotype. There were, however, no additive effects on the risk of stomach cancer between variants of the XRCC1gene and smoking,alcohol or pork oil consumption.ConclusionsThe effect of the XRCC1 gene homozygosity, particularly Arg/Arg, on the risk for stomach cancer was elevated by a high intake of vegetable oils and salt.

Meta-analysis of associations between XRCC1 gene polymorphisms and susceptibility to systemic lupus erythematosus and rheumatoid arthritis.

To determine whether X-ray repair cross-complementing group 1 (XRCC1) gene polymorphisms confer susceptibility to systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). A meta-analysis was conducted to determine the associations between XRCC1 gene polymorphisms and susceptibility to SLE and RA. A systematic literature search was conducted to identify all relevant studies. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to estimate the strength of the association. A total of nine case-control articles, consisting of five SLE and four RA articles, involving 1138 patients and 1399 healthy controls, were included in the meta-analysis. This meta-analysis showed no significant association of the Arg399Gln and Arg194Trp polymorphisms with SLE were found in all models when all study subjects were considered together. Stratification by ethnicity indicated the variant Arg399 (A) allele carriers increased the risk of SLE in Asians (A vs. G: OR = 1.402, 95% CI = 1.139-1.726, P = 0.001) and decreased the risk of SLE in Caucasians (A vs. G: OR = 0.769, 95% CI = 0.630-0.937, P = 0.009; AA vs. AG+GG: OR = 0.727, 95% CI = 0.554-0.953, P = 0.021). However, we failed to reveal any association between XRCC1 gene polymorphisms (Arg399Gln, Arg280His and Arg194Trp) and RA risk under all analysis models. Similar results were obtained in the subgroup analysis based on ethnicity. The present study suggests that the XRCC1 Arg399Gln polymorphism might be associated with genetic susceptibility to SLE in Asians and Caucasians, and there is no significant association between XRCC1 gene polymorphisms (Arg399Gln, Arg280His and Arg194Trp) and RA risk.

Association of XRCC1 and OGG1 DNA repair gene polymorphisms with rheumatoid arthritis in Egyptian patients

Rheumatoid arthritis (RA) is a chronic autoimmune disease and can lead to deformities and severe disabilities, due to irreversible damage of tendons, joints, and bones. Previous studies indicated that the DNA repair system was involved in the pathology of RA. In this study, we investigated the association of two XRCC1 (X-ray repair cross-complementing group 1) (rs25487 and rs25489) gene polymorphisms and two OGG1 (8-oxoguanine glycosylase 1) gene polymorphisms (rs159153 and rs3219008) with the susceptibility to RA in 320 Egyptians individuals (160 RA patients and 160 controls). Genotyping was performed using restriction fragment length polymorphism polymerase chain reaction. We found an association between variant XRCC1 (rs25487 and rs25489) genotype polymorphisms, OGG1 (rs3219008) genotype polymorphism, and RA disease susceptibility. Moreover, the presence of the Gln/Gln, Arg/His, and His/His genotypes of XRCC1 was significantly more likely to have bone erosion and extra-articular features in RA patients. Further, patient's carrying the OGG1 A/G and G/G genotypes more likely to have bone erosion. However, the AA genotype and A allele were significantly more likely to have extra-articular features. Also, there were no significant associations between C/T OGG1 gene polymorphism and RA susceptibility, bone erosion, and extra-articular features occurrence in RA patients. We concluded that the XRCC1-Arg/Gln, XRCC1-Arg/His, and OGG1 A/G polymorphism have a role in the development of rheumatoid arthritis disease. Also, these variant are associated with the severity of RA.

XRCC1 gene polymorphisms and glioma risk in Chinese population: a meta-analysis.

BackgroundThree extensively investigated polymorphisms (Arg399Gln, Arg194Trp, and Arg280His) in the X-ray repair cross-complementing group 1 (XRCC1) gene have been implicated in risk for glioma. However, the results from different studies remain inconsistent. To clarify these conflicts, we performed a quantitative synthesis of the evidence to elucidate these associations in the Chinese population.MethodsData were extracted from PubMed and EMBASE, with the last search up to August 21, 2014. Meta-analysis was performed by critically reviewing 8 studies for Arg399Gln (3062 cases and 3362 controls), 8 studies for Arg194Trp (3419 cases and 3680 controls), and 5 studies for Arg280His (2234 cases and 2380 controls). All of the statistical analyses were performed using the software program, STATA (version 11.0).ResultsOur analysis suggested that both Arg399Gln and Arg194Trp polymorphisms were significantly associated with increased risk of glioma (for Arg399Gln polymorphism: Gln/Gln vs. Arg/Arg, OR = 1.82, 95% CI = 1.46–2.27, P = 0.000; Arg/Gln vs. Arg/Arg, OR = 1.25, 95% CI = 1.10–1.42, P = 0.001 and for Arg194Trp polymorphism: recessive model, OR = 1.78, 95% CI = 1.44–2.19, P = 0.000), whereas the Arg280His polymorphism had no influence on the susceptibility to glioma in a Chinese population.ConclusionsThis meta-analysis suggests that there may be no association between the Arg280His polymorphism and glioma risk, whereas the Arg399Gln/Arg194Trp polymorphisms may contribute to genetic susceptibility to glioma in the Chinese population. Nevertheless, large-scale, well-designed and population-based studies are needed to further evaluate gene-gene and gene–environment interactions, as well as to measure the combined effects of these XRCC1 variants on glioma risk.

Association of XRCC1 genetic polymorphism with susceptibility to non-Hodgkin's lymphoma

The purpose of this study was to explore the association between X-ray repair cross-complementing group 1 (XRCC1)gene polymorphism and non-Hodgkin's lymphoma risk. A total of 282 non-Hodgkin's lymphoma (NHL) patients and 231 normal controls were used to investigate the effect of three XRCC1 gene polymorphisms (rs25487, rs25489, rs1799782) on susceptibility to non-Hodgkin's lymphoma. Genotyping was performed by using SNaPshot method. All statistical analyses were done with R software. Genotype and allele frequencies of XRCC1 were compared between the patients and controls by using the chi-square test. Crude and adjusted odd ratios and 95% confidence intervals were calculated by using logistic regression on the basis of genetic different models. For four kinds of NHL, subgroup analyses were also conducted. Combined genotype analyses of the three XRCC1 polymorphisms were also done by using logistic regression. The results showed that the variant genotype frequency was not significantly different between the controls and NHL or NHL subtype cases. Combined genotype analyses of XRCC1 399-280-194 results showed that the combined genotype was not associated with risk of NHL overall, but the VT-WT-WT combined genotype was associated with the decreased risk of T-NHL (OR: 0.21; 95%CI (0.06-0.8); P = 0.022), and the WT-VT-WT combined genotype was associated with the increased risk of FL(OR:15.23; 95%CI (1.69-137.39); P = 0.015). It is concluded that any studied polymorphism (rs25487, rs25489, rs1799782) alone was not shown to be rela-ted with the risk of NHL or each histologic subtype of NHL. The combined genotype with mutation of three SNP of XRCC1 was not related to the risk of NHL. However, further large-scale studies would be needed to confirm the association of decreased or increased risk for T-NHL and FL with the risk 3 combined SNP mutants of XRCC1 polymorphism.

Genetic polymorphisms in XRCC1 gene and susceptibility to glioma in Chinese Han population

Glioma is the most common type of primary brain malignancy in adults. The X-ray repair cross-complementing group 1 (XRCC1) is an important candidate gene for influencing the pathogenesis of glioma. This study aimed to evaluate the potential association between XRCC1 genetic polymorphisms and glioma susceptibility. This case-control study was conducted in Chinese Han populations consisting of 620 glioma cases and 630 cancer-free controls. XRCC1 genetic polymorphisms were detected by the polymerase chain reaction-restriction fragment length polymorphism and verified using DNA sequencing methods. The c.910A>G and c.1779C>G genetic polymorphisms were identified in this study. Our data suggested that the genotypes/alleles of these two genetic polymorphisms were statistically associated with the increased risk of glioma. As for c.910A>G, the risk of glioma for genotype GG was significantly higher than wild genotype AA (odds ratio (OR) = 1.98, 95% confidence interval (CI) 1.33-2.94, P = 0.001). As for c.1779C>G, the genotype GG was statistically associated with the increased risk of glioma compared to wild genotype CC (OR = 1.80, 95% CI 1.17-2.78, P = 0.007). Both of alleles G in c.910A>G and c.1779C>G may contribute to glioma susceptibility (G versus (vs.) A, OR = 1.30, 95% CI 1.09-1.54, P = 0.003; G vs. C, OR = 1.19, 95% CI 1.00-1.42, P = 0.045). Our findings indicate that the c.910A>G and c.1779C>G genetic polymorphisms are associated with the susceptibility to glioma in Chinese Han populations and might be used as molecular markers for evaluating glioma risk.

Association of XRCC1 Gene Polymorphisms with Breast Cancer Susceptibility in Saudi Patients

X-ray repair cross-complementing group 1 (XRCC1) plays a key role in the base excision repair pathway, as a scaffold protein that brings together proteins of the DNA repair complex. XRCC1 is reported to be a candidate influence on cancer risk. The aim of our present study was to assess the association of rs1799782 (Arg194Trp) and rs25487 (Arg399Gln) XRCC1 gene polymorphisms with breast cancer in the Saudi population. The two SNP's were analyzed in breast cancer patients and healthy control subjects. Genotypes were determined by TaqMan SNP genotype analysis technique and data were analyzed using Chi- square or t test and logistic regression analysis by SPSS16.0 software. Results showed that rs1799782 significantly increased susceptibility to breast cancer with Arg/Trp, Arg/Trp+Trp/Trp genotypes and at Trp allele overall study. It also increased risk of breast cancer in older age patients (above 48) and with the ER positive category. XRCC1rs25487 (Arg399Gln) did not showed any significant association. In conclusion the XRCC1rs1799782 polymorphism may be involved in the etiology of breast cancer in the Saudi population. Confirmation of our findings in larger populations of different ethnicities is warranted.

XRCC1 Gene Polymorphisms and the Risk of Differentiated Thyroid Carcinoma (DTC): A Meta-Analysis of Case-Control Studies

BackgroundPrevious studies investigating the association between X-ray repair cross-complementing group 1 (XRCC1) polymorphisms and thyroid cancer risk have yielded inconsistent results. This meta-analysis was performed to derive a more precise estimation of the relationship between three XRCC1 polymorphisms and thyroid cancer risk.Methods/Principal FindingsPubMed and EMBASE database were systematically searched to identify relevant studies. 10 publications were selected for this meta-analysis, including 11 studies for Arg399Gln polymorphism (1726 cases and 3774 controls), 7 studies for Arg194Trp polymorphism (1037 cases and 2487 controls) and 8 studies for Arg280His polymorphism (1432 cases and 3356 controls). The results in total population did not show any significant association between these three polymorphisms and the risk of DTC for all genetic models. However, when stratified by ethnicity, the results showed that Arg280His polymorphism was associated with an increased risk of DTC among Caucasians (Arg/His vs. Arg/Arg: OR = 1.45, 95% CI = 1.09–1.93; dominant model: OR = 1.43, 95% CI = 1.08–1.89; additive model: OR = 1.38, 95% CI = 1.05–1.80), whereas individuals carrying Arg/His genotype have a significantly reduced risk of DTC among Asians (Arg/His vs. Arg/Arg: OR = 0.71, 95% CI = 0.51–0.98). We also detected that 399Gln variant allele carriers might presented an overall decreased risk of DTC in mixed population. Furthermore, subgroup analyses by histological subtype revealed that Arg194Trp polymorphism was significantly associated with reduced risk for papillary thyroid carcinoma (PTC) (dominant model: OR = 0.71, 95% CI = 0.50–0.99).ConclusionsThis meta-analysis suggests that Arg280His polymorphism might contribute to the susceptibility of DTC among Caucasians, whereas it might provide protective effects in Asians against the risk of DTC. Additionally, our results support the protective role of Arg194Trp polymorphism in developing PTC, and show evidence of an association between Arg399Gln polymorphism and decreased risk of DTC in mixed population.

Predictive Value of Xrcc1 Gene Polymorphisms for Side Effects in Patients undergoing Whole Breast Radiotherapy: a Meta-analysis

Radiation-induced side effects on normal tissue are determined largely by the capacity of cells to repair radiation-induced DNA damage. X-ray repair cross-complementing group 1 (XRCC1) plays an important role in the repair of DNA single-strand breaks. Studies have shown conflicting results regarding the association between XRCC1 gene polymorphisms (Arg399Gln, Arg194Trp, -77T>C and Arg280His) and radiation-induced side effects in patients undergoing whole breast radiotherapy. Therefore, we conducted a meta-analysis to determine the predictive value of XRCC1 gene polymorphisms in this regard. Analysis of the 11 eligible studies comprising 2,199 cases showed that carriers of the XRCC1 399 Gln allele had a higher risk of radiation-induced toxicity than those with the 399 ArgArg genotype in studies based on high-quality genotyping methods [Gln vs. ArgArg: OR, 1.85; 95% CI, 1.20-2.86] or in studies with mixed treatment regimens of radiotherapy alone and in combination with chemotherapy [Gln vs. ArgArg: OR, 1.60; 95% CI, 1.09-2.23]. The XRCC1 Arg399Gln variant allele was associated with mixed acute and late adverse reactions when studies on late toxicity only were excluded [Gln allele vs. Arg allele: OR, 1.22; 95% CI, 1.00-1.49]. In contrast, the XRCC1 Arg280His variant allele was protective against radiation-induced toxicity in studies including patients treated by radiotherapy alone [His allele vs. Arg allele: OR, 0.58; 95% CI, 0.35-0.96]. Our results suggest that XRCC1 399Gln and XRCC1 280Arg may be independent predictors of radiation-induced toxicity in post-surgical breast cancer patients, and the selection of genotyping method is an important factor in determining risk factors. No evidence for any predictive value of XRCC1 Arg194Trp and XRCC1 -77T>C was found. So, larger and well-designed studies might be required to further evaluate the predictive value of XRCC1 gene variation on radiation-induced side effects in patients undergoing whole breast radiotherapy.

Predictive Value of XRCC1 Gene Polymorphisms on Platinum-Based Chemotherapy in Advanced Non–Small Cell Lung Cancer Patients: A Systematic Review and Meta-analysis

Published data have shown conflicting results about the relationship between X-ray repair cross-complementing group 1 (XRCC1) gene polymorphisms (Arg399Gln and Arg194Trp) and clinical outcome of platinum-based chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). A meta-analysis is needed to provide a systematic review of the published findings. We conducted a systematic review and meta-analysis to evaluate the predictive value of XRCC1 gene polymorphisms on clinical outcome up to October 1, 2010. The quality of each study was scored on the basis of predefined criteria. A total of 13 eligible follow-up studies met all the inclusion criteria. The XRCC1194Trp allele was found to be significantly associated with a favorable response rate relative to 194Arg [Trp vs. Arg: OR, 1.88; 95% confidence interval (CI), 1.48-2.38]. XRCC1399Gln was less favorably associated with both response rate (Gln vs. Arg: OR, 0.67; 95% CI, 0.52-0.87) and overall survival (Gln vs. Arg: HR, 1.30; 95% CI, 1.04-1.63) than 399Arg in analyses using all available studies; but these associations became insignificant when only high-quality studies were used. These findings suggest a predictive role for XRCC1 gene polymorphisms in clinical outcome. However, the role of 399Gln could be considered controversial because its impact on clinical outcome was insignificant in high-quality studies. These findings show the importance of establishing suitable criteria, including genetic epidemiologic, phenotypic, and clinical criteria, to improve quality control of study design and methods in pharmacogenomic studies related to XRCC1 gene polymorphism.

DNA repair gene XRCC1 polymorphisms and the risk of asthma in a Turkish population

Polymorphisms have been identified in several DNA damage repair genes. These polymorphisms may effect DNA repair capacity and modulate asthma susceptibility. In this study, we aimed to determine the two polymorphisms in DNA repair gene, x-ray repair cross-complementing group 1 (XRCC1), in a sample of Turkish patients with asthma, and evaluate their association with asthma development. We used polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) to analyze XRCC1 Arg194Trp and XRCC1 Arg399Gln polymorphisms in 116 patients with asthma and in 180 disease-free controls. Our data showed a positive association between the polymorphisms of codons 194 (odds ratio [OR] = 1.97, 95% confidence interval [CI] = 1.06-3.66, and p = 0.03 for Arg/Trp genotype) and 399 (OR = 1.87, 95% CI = 1.12-3.13, and p = 0.02 for Arg/Gln genotype, and OR = 2.59, 95% CI = 1.24-5.43, and p = 0.01 for Gln/Gln genotype) and asthma risk. No statistically significant difference was found for the allelic and genotypic distributions of the polymorphisms in XRCC1 gene between mild and moderate asthmatic patients. A combined analysis of the effect of XRCC1 codons 194 and 399 revealed the highest risk (OR = 4.17, 95% CI = 1.77-9.83, and p = 0.001) for carriers of the polymorphic alleles in both of these codons. These results suggest that the risk of asthma may be associated with DNA repair mechanisms, and understanding these mechanisms will help identify individuals at increased risk of developing asthma and should lead to improved treatment of asthma.

Association study between XRCC1 gene polymorphisms and sporadic amyotrophic lateral sclerosis

The aim of the present study was to investigate the possible contribution of three common functional polymorphisms in the DNA repair protein X-ray repair cross-complementing group 1 (XRCC1), namely Arg194Trp (rs1799782), Arg280His (rs25489) and Arg399Gln (rs25487), to sporadic amyotrophic lateral sclerosis (SALS). We genotyped 206 Italian SALS patients and 203 matched controls for XRCC1 Arg194Trp, Arg280His and Arg399Gln polymorphisms by means of PCR/RFLP technique, searching for association between any of the studied polymorphisms and disease risk, age and site of onset. We observed a statistically significant difference in XRCC1 Gln399 allele frequencies between SALS cases and controls (0.39/0.28; p=0.001). The present study suggests that the XRCC1 Arg399Gln polymorphism might contribute to SALS risk.

XRCC1 gene polymorphisms and esophageal squamous cell carcinoma risk in Chinese population: A meta‐analysis of case–control studies

Two non-synonymous polymorphisms Arg194Trp and Arg399Gln in the DNA-base excision repair gene X-ray repair cross-complementing group 1 (XRCC1) have been implicated in risk for esophageal cancer. However, the results from different studies remain controversial. The present meta-analysis of literatures was performed to clarify these associations in Chinese population. A comprehensive literature search was conducted to identify all case-control studies of XRCC1 polymorphisms Arg194Trp and Arg399Gln and risk for esophageal squamous cell carcinoma (ESCC). A total of 9 eligible studies, including 1,538 ESCC cases and 2,472 controls, were identified to the meta-analysis. The odds ratio (OR) for the variant homozygous genotype Trp/Trp of the Arg194Trp polymorphism, compared with the wild-type homozygote Arg/Arg, was 1.59 (p = 0.0007), with 95% confidence interval (95% CI) 1.22-2.09, for ESCC risk without between-study heterogeneity. However, there was no statistically significant associations of ESCC risk in the dominant model Arg/Trp+Trp/Trp (OR 0.97; 95% CI 0.84-1.12; p = 0.69) and heterozygous genotype Arg/Trp (OR 0.90; 95% CI 0.77-1.04; p = 0.16) when comparing with wild-type genotype Arg/Arg. For Arg399Gln, there was no effect in dominant modeling (Arg/Gln+Gln/Gln vs. Arg/Arg: OR 0.92; 95% CI 0.80-1.06; p = 0.25), and the variant Gln/Gln homozygote was not associated with ESCC risk (OR 1.29; 95% CI 0.79-2.10; p = 0.31), either. In conclusion, Arg194Trp genetic polymorphism may be associated with an increased risk for developing ESCC and a study with the larger sample size is needed to further evaluate gene-environment interaction on XRCC1 polymorphisms and ESCC risk.

XRCC1 gene polymorphisms in a population sample and in women with a family history of breast cancer from Rio de Janeiro (Brazil)

The X-ray repair cross-complementing Group1 (XRCC1) gene has been defined as essential in the base excision repair (BER) and single-strand break repair processes. This gene is highly polymorphic, and the most extensively studied genetic changes are in exon 6 (Arg194Trp) and in exon 10 (Arg399Gln). These changes, in conserved protein sites, may alter the base excision repair capacity, increasing the susceptibility to adverse health conditions, including cancer. In the present study, we estimated the frequencies of the XRCC1 gene polymorphisms Arg194Trp and Arg399Gln in healthy individuals and also in women at risk of breast cancer due to family history from Rio de Janeiro. The common genotypes in both positions (194 and 399) were the most frequent in this Brazilian sample. Although the 194Trp variant was overrepresented in women reporting familial cases of breast cancer, no statistically significant differences concerning genotype distribution or intragenic interactions were found between this group and the controls. Thus, in the population analyzed by us, variants Arg194Trp and Arg399Gln did not appear to have any impact on breast cancer susceptibility.