X-ray Repair Cross-complementing Group 1 Arg194Trp Research Articles

The XRCC1 Arg194Trp polymorphism was associated with the risk of head and neck squamous cell carcinoma development: Results from a systematic review and meta-analysis.

The X-ray repair cross complementing group 1 (XRCC1) is a DNA repair gene. Various studies have examined the association between XRCC1 Arg194Trp polymorphism and head and neck squamous cell carcinoma (HNSCC) susceptibility with contradictory results. So, this systematic review and meta-analysis aimed to assess whether variants of this polymorphism increase the HNSCC risk or not. Thirty three studies consisting of 14282 subjects (6012 cases and 8270 controls) were included in this meta-analysis. Variants of XRCC1 Arg194Trp polymorphism were associated with increased HNSCC risk and the associations were significant based on heterozygous and dominant models (heterozygous model: OR = 1.182, 95%CI = 1.015-1.377, P = 0.032; homozygous model: OR = 1.274, 95%CI = 0.940-1.727, P = 0.119; dominant model: OR = 1.194, 95%CI = 1.027-1.388, P = 0.021; recessive model: OR = 1.181, 95%CI = 0.885-1.576, P = 0.119). There were significant associations between variants of this polymorphism and HNSCC risk based on Asian ethnicity under dominant model, hospital control source under different genetic models, PCR-RFLP genotyping method under dominant model and oral cavity tumor site under heterozygous and dominant models. The X-ray repair cross complementing group 1 (XRCC1) is a DNA repair gene. Various studies have examined the association between XRCC1 Arg194Trp polymorphism and head and neck squamous cell carcinoma (HNSCC) susceptibility with contradictory results. So, this systematic review and meta-analysis aimed to assess whether variants of this polymorphism increase the HNSCC risk or not. A systematic search of the literatures published till April 2022 was conducted using Google Scholar, Scopus, PubMed, Web of Science, Cochrane Library and Embase databases. The heterogeneity was assessed with the I-Square statistic. A random effects model or fixed effects model was used to analyze the data. Data were reported by odds ratio (OR) and 95% confidence interval (CI). The p value was considered significant if p < .05. Thirty three studies consisting of 14 282 subjects (6012 cases and 8270 controls) were included in this meta-analysis. Variants of XRCC1 Arg194Trp polymorphism were associated with increased HNSCC risk and the associations were significant based on heterozygous and dominant models (heterozygous model: OR=1.182, 95%CI=1.015-1.377, p=.032; homozygous model: OR=1.274, 95%CI=0.940-1.727, p=.119; dominant model: OR=1.194, 95%CI=1.027-1.388, p=.021; recessive model: OR=1.181, 95%CI=0.885-1.576, p=.119). There were significant associations between variants of this polymorphism and HNSCC risk based on Asian ethnicity under dominant model, hospital control source under different genetic models, PCR-RFLP genotyping method under dominant model and oral cavity tumor site under heterozygous and dominant models. Variants of XRCC1 Arg194Trp polymorphism were significantly associated with increased risk of HNSCC development based on heterozygous and dominant genetic models.

Impact of XRCC1 genetic variants on its tissue expression and breast cancer risk: A case-control study.

X-ray repair cross-complementing group 1 (XRCC1), a coordinator protein of the DNA repair complex, is thought to be involved in cancer progression. This case-control study aimed to investigate the association of two biallelic single-nucleotide polymorphisms (SNPs; Arg399Gln, Arg194Trp) of the XRCC1 gene with its tissue expression level and breast cancer (BC) risk in Egyptian women. This study included 100 BC female patients (case group 1) and 100 healthy females (control group 2). The XRCC1 tissue expression was assessed by immunohistochemistry (IHC). Genotyping of the two XRCC1 SNPs (Arg399Gln, Arg194Trp) using real-time polymerase chain reaction (PCR) was also conducted. The XRCC1 expression level was significantly lower in cancerous tissues than adjacent non-cancerous tissues (p < .001). The XRCC1 399Gln/Gln genotype, 399Gln allele, the dominant, and recessive models were significantly associated with lower XRCC1 expression in breast cancerous tissues and increased risk for BC (3.390-, 1.965-, 2.241-, and 2.429-folds, respectively). The XRCC1 399Gln/Gln genotype was associated with lower incidence of advanced tumor grade (OR: 0.06; 95%CI: 0.01-0.74; p=.028). Conversely, the XRCC1 Arg194Trp polymorphism did not show any significant association with either XRCC1 expression in breast cancer tissues or BC risk in all genetic models. The XRCC1 haplotypes, 399Gln/194Arg and 399Gln/194Trp, were associated with 1.800- and 1.675-folds risk for BC, respectively. The XRCC1 gene polymorphism (Arg399Gln) is associated with reduced XRCC1 tissue expression and enhanced BC risk with a well-differentiated nature in Egyptian women. Moreover, XRCC1 haplotypes, 399Gln/194Arg and 399Gln/194Trp, were associated with increased BC risk.

Genetic and biochemical studies of hepatic carcinoma in the Egyptian population.

Background:Hepatocellular carcinoma (HCC), a deadly malignancy of the liver, is considered the third leading reason behind cancer deaths. It is more frequent in men than in women of ages above 50. Liver disease, leading to liver cirrhosis (LC), is mostly caused by alcoholism abuse, reaction diseases of the liver, or viral hepatitis B or C infection. Interleukin-6 (IL-6) is considered an effective pro-inflammatory cytokine, which plays a crucial role in the host defense mechanism. Its level is higher in HCC patients than in LC cases, indicating that tumor cells increase the production of cytokines. The X-ray repair cross-complementing group 1 (XRCC1) gene is a major DNA repair gene. It acts as a scaffold of various activities that are concerned in the repairing method by interacting with components of base excision repair. This study aims to measure the serum concentrations of IL6 and C-reactive protein (CRP) and investigate whether XRCC1 Arg194Trp and Arg399Gln polymorphisms are related to HCC disease.Materials and Methods:Whole-blood DNA was extracted from 123 HCC patients and 123 healthy volunteers. Tetra-primer amplification refractory mutation system was performed in the detection of XRCC1 Arg399Gln and Arg194Trp polymorphisms.Results:Serum concentration levels of IL-6 and CRP are significantly higher in patients with HCC than in control subjects. The allelic and genotype frequency distributions of XRCC1 (Arg399Gln and Arg194Trp) are significantly increased in HCC cases compared to healthy volunteers.Conclusion:Arg/Gln, Arg/Trp, Gln/Gln, and Trp/Trp genotypes are associated with higher risk HCC than the Arg/Arg genotype.

Association between polymorphisms in the XRCC1 gene and male infertility risk: A meta-analysis.

Background:X-ray repair cross-complementing group 1 (XRCC1) single nucleotide polymorphisms (SNPs) might correlate with male infertility susceptibility. This association has been described; however, the findings remain inconsistent. Consequently, this meta-analysis was conducted to characterize the relationship between XRCC1 SNPs and male infertility susceptibility.Methods/main results:Studies were systematically searched in databases to evaluate the association between SNPs of XRCC1 and infertility in males. The effect measures chosen were the 95% confidence intervals (95% CIs) and odds ratios (ORs). A total of 7 studies, including 6 case-controlled studies on XRCC1 Arg399Gln and 3 case-controlled studies on XRCC1 Arg194Trp, were included. Ultimately, the results of this analysis revealed that XRCC1 Arg399Gln SNPs were significantly associated with infertility in males in homozygote comparisons (GG vs GA+AA: OR = 0.614, 95% CI: 0.40–0.937, P = .024). This meta-analysis did not demonstrate a relationship between XRCC1 Arg194Trp and male infertility risk.Conclusions:Our study indicated that XRCC1 Arg399Gln polymorphism was associated with a significantly decreased male infertility risk, but not XRCC1 Arg194Trp.

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.

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 polymorphism XRCC1 Arg194Trp and 8-hydroxydeoxyguanosine increased susceptibility to arsenic-related renal cell carcinoma

This study was designed to explore the relationship between X-ray repair cross-complementing group 1 (XRCC1) gene polymorphisms and renal cell carcinoma (RCC) and to investigate whether individuals with an XRCC1 risk genotype, a high level of 8-OHdG or a high urinary total arsenic concentration have a modified odds ratio (OR) of RCC. We recruited 180 RCC patients and 360 age- and sex-matched controls from a hospital-based pool. Image-guided biopsy or surgical resection of renal tumors was performed on RCC patients for pathological verification. Genomic DNA was used to examine the genotype of XRCC1(Arg399Gln), XRCC1(Arg194Trp), XRCC3(Thr241Met) and XPD(Lys751Gln) by PCR-RFLP. Liquid chromatography with tandem mass spectrometry was used to determine urinary 8-OHdG levels. A HPLC-HG-AAS was used to determine the concentrations of urinary arsenic species. Participants with the genotype XRCC1(Arg194Trp) Arg/Trp+Trp/Trp had a significantly higher OR of RCC than those with the Arg/Arg genotype; the OR and 95% confidence interval was 0.66 (0.45–0.97) after multivariate adjustment. The OR of RCC for the combined effect of high urinary 8-OHdG levels and high urinary total arsenic concentration in individuals with a XRCC1(Arg194Trp) Arg/Trp+Trp/Trp genotype was higher than in patients with an Arg/Arg genotype, which was evident in a dose response manner. In conclusion, this is the first study to show that the XRCC1 Arg194 allele is a predicting factor for RCC. The more risk factors (high urinary 8-OHdG levels, high urinary total arsenic concentrations, and XRCC1 Arg194 allele) that were present, the higher the OR of RCC.

GSTP1 Ile105Val and XRCC1 Arg399Gln gene polymorphisms contribute to the clinical outcome of patients with advanced non-small cell lung cancer.

Glutathione S-transferase P1 (GSTP1) and X-ray repair cross-complementing group 1 (XRCC1) genetic variations may in-fluence the efficacy of chemotherapy in various cancers. We investi-gated the possible roles of GSTP1 Ile105Val and XRCC1 Arg194Trp, and Arg399Gln gene polymorphisms in the prognosis of advanced non-small cell lung carcinoma (NSCLC) patients with cisplatin-based chemotherapy. Between January 2010 and December 2012, this study consecutively recruited 141 patients with advanced NSCLC from the First People's Hospital of Yunnan Province. Logistic regression analy-sis showed that individuals carrying the GG genotype were associated with a better response to chemotherapy than those with the wide-type genotype, with an adjusted odds ratio (95% confidence interval, CI) of 4.07 (1.06-25.06). Moreover, we observed that the AA genotype of XRCC1 Arg399Gln was correlated with a greater complete response + partial response to chemotherapy than that with the GG genotype (odds ratio = 2.71, 95%CI = 1.13-10.08). Based on the Cox hazard proportional model, the GG genotype of GSTP1 Ile105Val was found to be associated with a lower risk of death from all causes as compared to that with the AA genotype (hazard ratio = 0.07, 95%CI = 0.01-0.34). In summary, we suggest that GSTP1 Ile105Val and XRCC1 Arg399Gln polymorphisms could influence the response to chemotherapy and sur-vival of advanced NSCLC.

Association between the X-ray repair cross-complementing group 1 Arg194Trp polymorphism and thyroid carcinoma susceptibility: A meta-analysis

Previous case-control studies having investigated the relationship between the X-ray repair cross-complementing group 1 (XRCC1) Arg194Trp polymorphism and thyroid cancer (TC) have drawn inconsistent conclusions. The current study aimed to clarify the role of this polymorphism in susceptibility to TC. An up-to-date search of PubMed and Web of Science databases was conducted, including articles published up to August 2015. Crude odds ratios (ORs) with 95%CIs were calculated to establish the association between the XRCC1 Arg194Trp polymorphism and TC risk. Five studies were used, comprising 911 patients and 1476 controls. Our meta-analysis indicated that this polymorphism is associated with TC risk in Caucasians (TrpTrp vs ArgArg: OR = 5.72, 95%CI = 1.39-23.54; ArgTrp vs ArgArg: OR = 1.20, 95%CI = 0.87-1.66; dominant model: OR = 1.31, 95%CI = 0.96-1.79; recessive model: OR = 0.18, 95%CI = 0.04-0.73). This investigation demonstrates that the XRCC1 Arg194Trp polymorphism constitutes a risk factor for TC in Caucasian individuals.

Abstract 3857: The polymorphisms of XRCC1 Arg194Trp and the XRCC1Arg399Gln affect the clinical features and the prognosis of MDS

Abstract Background: X-ray repair cross-complementing group 1 (XRCC1) is involved an important role in base excision repair (BER) system of DNA repair. Polymorphism in DNA repair genes may be modified of DNA repair capacity. However, it is unclear that the polymorphisms of XRCC1alter the clinical features of MDS patients. Our study was performed to evaluate the effect of the XRCC1Arg194Trp and the XRCC1Arg399Gln with the susceptibility and clinical features of MDS. Methods: We genotyped the polymorphisms by using polymerase chain reaction -restriction fragment-length polymorphism (PCR-RFLP) analysis in 119 patients with MDS [median 67.9 years, range 17.1-86.5 years; male/female 81/38; RCUD (n = 40), RARS (n = 6), RCMD (n = 21), MDS-U (n = 13), RAEB-1(n = 14), RAEB-2 (n = 12), others (n = 13)] and 202-health controls. Results: In the allele and genotype frequencies of the XRCC1Arg194Trp and the XRCC1Arg399Gln were not statistically significant difference in patients and the controls. However, Arg/Arg genotypes of XRCC1 194 and the XRCC1 399 were significantly associated with lower Hb. In addition, XRCC1 399 non Arg/Arg genotype was significantly associated with previous history of radiotherapy and multiple cancers. Furthermore, XRCC1Arg194Trp non Arg/Arg genotype and XRCC1Arg399Gln Arg/Arg genotype were significantly associated with poor prognosis of MDS patients. Conclusion: We found that the polymorphisms of XRCC1 may be affected the clinical features and the prognosis of MDS. Citation Format: Batchimeg Norjmaa, Takayuki Saitoh, Tetsuhiro Kasamatsu, Yusuke Minato, Noriaki Sunaga, Hirokazu Murakami. The polymorphisms of XRCC1 Arg194Trp and the XRCC1Arg399Gln affect the clinical features and the prognosis of MDS. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3857. doi:10.1158/1538-7445.AM2015-3857

Effect of X-ray repair cross complementing group 1 polymorphisms on the efficacy of platinum-based chemotherapy in patients with nonsmall cell lung cancer.

X-ray repair cross complementing group 1 (XRCC1) has been indicated to be correlated with the efficacy of platinum-based chemotherapy. But study results were still debatable. Thus, a meta-analysis was conducted. A literature search was performed using the PubMed, EMBASE, CNKI, with the databases being last accessed on November 24, 2014. Odds ratios with 95% confidence intervals were used to assess the strength of the association. In this meta-analysis, we found that XRCC1 Arg194Trp polymorphism was significantly associated with the efficacy of platinum-based chemotherapy. However, XRCC1 Arg399Gln polymorphism showed no impact on the efficacy of platinum-based chemotherapy. This meta-analysis suggested that the XRCC1 Arg194Trp polymorphism may be associated with efficacy of platinum-based chemotherapy. Further studies with a larger sample size are needed to further assess this result.

No association between XRCC1 genetic polymorphisms and differentiated thyroid carcinoma risk: a meta-analysis.

The X-ray repair cross-complementing group 1 (XRCC1) gene belongs to the family of DNA repair genes. Polymorphisms in the XRCC1 gene, Arg399Gln, Arg194Trp and Arg280His, have been reported to have implications in differentiated thyroid carcinoma (DTC) susceptibility, but the results remain conflicting and no meta-analysis has been published. Therefore, we carried out a systematic review of the published epidemiology studies, aiming to assess the relationship between XRCC1 polymorphisms and susceptibility to DTC risk. We selected three databases, PubMed, EMBASE and CNKI, in which to search for published literature. With respect to DTC risk associated with XRCC1, combined odds ratios (ORs) and 95% confidence intervals (CI) were appropriately calculated on the basis of co-dominant, dominant and recessive models. To investigate different effects from specific race, subgroup analyses were carried out in Asian and Caucasian populations. Eight studies meeting the inclusion criteria were eventually selected for Arg399Gln (1,550 cases and 2,692 controls), five studies for Arg194Trp (858 cases and 1,394 controls) and five studies for Arg280His (1,237 cases and 2,267 controls). The combined results of the relevant studies exhibited that no significant associations with DTC risk were demonstrated for polymorphisms in XRCC1 Arg399Gln, Arg194Trp and Arg280His in all genetic models. Stratified analyses in Asian and Caucasian populations showed similar results. This meta-analysis arrives at a conclusion that the XRCC1 (Arg399Gln, Arg194Trp, Arg280His) polymorphisms appear to confer no risk for DTC.

DNA repair gene XRCC1 Arg194Trp polymorphism and susceptibility to hepatocellular carcinoma: A meta-analysis.

The arginine194tryptophan (Arg194Trp) polymorphism in the X-ray repair cross-complementing group 1 (XRCC1) gene has been reported to be associated with hepatocellular carcinoma (HCC), however, the results from previous studies are conflicting. The present study aimed to investigate the association between the XRCC1 Arg194Trp polymorphism and the risk of HCC, using a meta-analysis of previously published studies. PubMed (http://www.ncbi.nlm.nih.gov/pubmed/), Google Scholar (http://scholar.google.co.uk/) and the China National Knowledge Infrastructure databases (http://www.cnki.net/) were systematically searched to identify relevant studies published prior to October 2013. A meta-analysis was performed to examine the association between the Arg194Trp gene polymorphism and the susceptibility to HCC. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. The meta-analysis consisted of six case-control studies that included 1,451 HCC cases and 1,398 healthy controls. Meta-analysis results based on all the studies showed no significant association between the XRCC1 Arg194Trp gene polymorphism and the risk of HCC (Trp/Trp vs. Arg/Arg: OR, 1.17; 95% CI, 0.89–1.55; Trp/Trp vs. Arg/Trp: OR, 0.94; 95% CI, 0.59–1.51; dominant model: OR, 0.97; 95% CI, 0.63–1.49; recessive model: OR, 1.22; 95% CI, 0.89–1.67). In the subgroup analysis, three studies with sample sizes of >300 produced similar results that indicated that the Arg194Trp gene polymorphism had no association with an increased or decreased risk of HCC. The pooled ORs were not markedly different following the exclusion of two studies deviating from the Hardy-Weinberg equilibrium in the control group, which indicated the reliability of the meta-analysis results. In conclusion, the XRCC1 Arg194Trp polymorphism may not be a risk or protective factor for HCC. Further large and well-designed studies are required to confirm these results.

No association between XRCC1 gene Arg194Trp polymorphism and risk of lung cancer: evidence based on an updated cumulative meta-analysis

X-ray repair cross-complementing group 1 (XRCC1) gene Arg194Trp polymorphism has been reported to be associated with risk of lung cancer in many published studies. Nevertheless, the research results were inconclusive and conflicting. To reach conclusive results, several meta-analysis studies were conducted by combining results from literature reports through pooling analysis. However, these previous meta-analysis studies were still not consistent. Hence, we used an updated and cumulative meta-analysis to get a more comprehensive and precise result from 25 case–control studies searching through the PubMed database up to September 1, 2013. The meta-analysis was carried out by the Comprehensive Meta-Analysis software and the odds ratio (OR) with 95 % confidence interval (CI) was used to estimate the pooled effect. The result involving 8,876 lung cancer patients and 11,210 controls revealed that XRCC1 Arg194Trp polymorphism was not associated with lung cancer risk [(OR = 0.97, 95 %CI = 0.92–1.03) for Trp vs. Arg; (OR = 0.92, 95 % CI = 0.85–0.98) for ArgTrp vs. ArgArg; (OR = 1.07, 95 % CI = 0.92–1.23) for TrpTrp vs. ArgArg; (OR = 0.93, 95 % CI = 0.87–1.00) for (TrpTrp + ArgTrp) vs. ArgArg; and (OR = 1.08, 95 % CI = 0.94–1.25) for TrpTrp vs. (ArgTrp + ArgArg)]. The cumulative meta-analysis showed that the results maintained the same, while the ORs with 95 % CI were more stable with the accumulation of case–control studies. The sensitivity and subgroups analyses showed that the results were robust and not affected by any single study with no publication bias. Relevant studies might not be needed for supporting these results.

Association between X-ray repair cross-complementing group 1 Arg194Trp polymorphism and prostate cancer risk

X-ray repair cross-complementing group 1 (XRCC1) plays an important role in the maintenance of the genomic integrity. Previous studies on the association between XRCC1 Arg194Trp polymorphism and prostate cancer risk reported conflicting results. To get a more precise assessment of the association between XRCC1 Arg194Trp polymorphism and prostate cancer risk, we performed a meta-analysis of previously published studies. Eligible studies were searched in PubMed, Embase, and China National Knowledge Infrastructure (CNKI) databases. Nine studies with a total of 5,407 subjects were finally included into the meta-analysis. Odds ratio (OR) with 95% confidence interval (95%CI) was used to assess the association. Overall, there was no obvious association between XRCC1 Arg194Trp polymorphism and prostate cancer risk (Trp vs. Arg: OR = 1.02, 95%CI 0.84-1.25, P = 0.824; TrpTrp vs. ArgArg: OR = 1.17, 95%CI 0.83-1.66, P = 0.374; TrpTrp/ArgTrp vs. ArgArg: OR = 1.00, 95%CI 0.79-1.28, P = 0.990; TrpTrp vs. ArgArg/ArgTrp: OR = 1.20, 95%CI 0.85-1.68, P = 0.301). Subgroup analysis according to ethnicity also detected no significant association in both Asians and Caucasians. In conclusion, the meta-analysis suggests that there is no obvious association between XRCC1 Arg194Trp polymorphism and prostate cancer risk.

Association of X-Ray Repair Cross-Complementing Group 1 Arg194Trp, Arg399Gln and Arg280His Polymorphisms with Head and Neck Cancer Susceptibility: A Meta-Analysis

BackgroundPrevious studies on the association of X-ray repair cross-complementing group 1 (XRCC1) Arg194Trp, Arg399Gln, and Arg280His polymorphisms with head and neck cancer (HNC) have produced inconsistent results. The aim of the present study was to evaluate the effects of these three polymorphic variants on HNC risk.MethodsThe PubMed and EMBASE databases were searched for genetic association studies on the XRCC1 Arg194Trp, Arg399Gln, and Arg280His polymorphisms and HNC risk. (The most recent search was conducted on 20 August, 2013.) Twenty-six studies were identified and meta-analysis was performed to evaluate the association between the polymorphism and HNC by calculating combined odds ratios and 95% confidence intervals.ResultsNo significant association was found under the allelic, homozygous, heterozygote, and dominant genetic models in the overall comparison. Further, no significant association between the XRCC1 Arg399Gln and Arg280His polymorphisms and HNC risk was detected under the four genetic models in subgroup analyses based on ethnicity, cancer site, and whether or not the studies had been adjusted for cigarette smoking and alcohol. However, in stratified analyses based on cancer site, a significant association was found between the XRCC1 Arg194Trp polymorphism and oral cancer under the allelic, heterozygote, and dominant models. The XRCC1 Arg194Trp polymorphism was significantly associated with HNC risk in studies that were adjusted for smoking and alcohol under the homozygous and heterozygote models.ConclusionThe meta-analysis results suggest that the XRCC1 Arg399Gln and Arg280His polymorphisms are probably not associated with the risk of HNC, but the XRCC1 Arg194Trp polymorphism was associated with increased risk of HNC in the subgroup analysis of studies adjusted for smoking and alcohol and with increased risk of oral cancer in the stratified analyses based on cancer site. Further studies with larger samples are needed to confirm these findings.

Association of XRCC1 polymorphisms with thyroid cancer risk

Due to the important role in the DNA repair pathways, numerous studies have been carried out to explore the relationship between the polymorphisms in the X-ray repair cross-complementing group 1 (XRCC1) gene and thyroid cancer risk. But previous reports have produced conflicting results. Thus, we performed an updated comprehensive meta-analysis to better investigate the association of the XRCC1 polymorphisms with thyroid cancer risk. There were a total of nine studies included with 1,621 cases and 3,669 controls examining the effects of the XRCC1 Arg280His, Arg399Gln, and Arg194Trp polymorphisms on the susceptibility of thyroid cancer. In our study, the XRCC1 Arg280His polymorphism was found to be associated with an increased thyroid cancer risk in the Caucasian population [allelic contrast: odds ratio (OR) = 1.38, 95% CI = 1.05-1.80, P(Z) = 0.02, P(Q) = 0.61; dominant model: OR = 1.43, 95% CI = 1.08-1.89, P(Z) = 0.01, P(Q) = 0.57]. The Arg399Gln polymorphism was associated with a significant decreased risk [allelic contrast: OR = 0.73, 95% CI = 0.59-0.92, P(Z) = 0.006, P(Q) = 0.31; dominant model: OR = 0.73, 95% CI = 0.55-0.97, P(Z) = 0.03, P(Q) = 0.33; recessive model: OR = 0.56, 95% CI = 0.34-0.93, P(Z) = 0.02, P(Q) = 0.59], while the Arg194Trp SNP conferred an increased risk for thyroid cancer in the mixed populations [allelic contrast: OR = 1.49, 95% CI = 1.02-2.17, P(Z) = 0.04]. To conclude, the present meta-analysis demonstrated that the polymorphisms in the XRCC1 gene may be associated with developing of thyroid cancer.

Polymorphisms in the XRCC1 gene are associated with treatment response to platinum chemotherapy in advanced non-small cell lung cancer patients based on meta-analysis.

X-ray repair cross complementing group 1(XRCC1) polymorphisms have been implicated in interindividual variability of efficacy of platinum chemotherapy for treating non-small cell lung cancer (NSCLC); however, results of different studies have been inconsistent. We conducted a meta-analysis to investigate the association between polymorphisms in the XRCC1 gene and response rate of platinum chemotherapy in advanced NSCLC patients. Searches were performed on MEDLINE, PubMed, EMBASE, Chinese Biological Medicine Database, China National Knowledge Infrastructure, and Wangfang Data, covering all relevant studies published up to August 1, 2012. Statistical analyses were performed using the Revman 5.0 and STATA 10.0 software. Two polymorphisms, Arg399Gln (G>A) and Arg194Trp (C>T), were investigated in 19 studies, involving 2152 advanced NSCLC patients. For XRCC1 Arg399Gln, patients carrying two G alleles had a significantly increased response rate of platinum chemotherapy, when compared with those carrying the A allele [odds ratio (OR) = 2.05, 95% confidence interval CI = 1.62-2.60 for GG vs GA+AA]. Similarly, the AA carriers had a 54% decreased response rate compared with the G allele carriers (OR = 0.46, 95%CI = 0.30-0.70 for AA vs GA+GG). For XRCC1 Arg194Trp, patients carrying two C alleles had a 62% decreased response rate compared with those carrying either one or two variant T alleles (OR = 0.38, 95%CI = 0.30-0.48 for CC vs CT+TT). However, although TT carriers had a better response rate compared with the C allele carriers, the difference was not significant (OR = 1.27, 95%CI = 0.92-1.77 for TT vs CC+CT). Based on this meta-analysis, we conclude that XRCC1 polymorphisms are associated with treatment response to platinum chemotherapy in advanced NSCLC patients.

DNA Repair Gene XRCC1 Polymorphisms and Head and Neck Cancer Risk: An Updated Meta-Analysis Including 16344 Subjects

BackgroundDNA repair gene X-ray repair cross complementing group 1 (XRCC1) plays an important role in the maintenance of the genomic integrity and protection of cells from DNA damage. Sequence variation in XRCC1 gene may alter head and neck cancer (HNC) susceptibility. However, these results are inconclusive. To derive a more precise estimation of the relationship between XRCC1 polymorphism and HNC risk, we undertook a meta-analysis involving 16,344 subjects.MethodsA search of the literature by PubMed, Embase, Web of Science and China National Knowledge Infrastructure was performed to identify studies based on the predetermined inclusion criteria. The odds ratio (OR) with 95% confidence interval (CI) was combined using a random-effects model or a fixed-effects model.ResultsTwenty-nine studies consisting of 6,719 cases and 9,627 controls were identified and analyzed. Overall, no evidence of significant association was observed between XRCC1 Arg194Trp, XRCC1 Arg280His, XRCC1 Arg399Gln genotypes and the risk of HNC in any genetic models. Subgroup analyses according to ethnicity, tumor site, publication year, genotyping method also detected no significant association in any subgroup, except that oral cancer was associated with Arg194Trp variant in recessive model. Furthermore, no significant effect of these polymorphisms interacted with smoking on HNC risk was detected but Arg194Trp homozygous variant.ConclusionIn conclusion, this meta-analysis suggests that the XRCC1 Arg194Trp, Arg280His and Arg399Gln polymorphism may not involve in HNC susceptibility. Further studies about gene-gene and gene-environment interactions in different populations are required.