X-ray Repair Cross-complementing Group 1 Arg194Trp Polymorphism 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.

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.

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.

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.

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.

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

The polymorphism of X-ray repair cross-complementing group 1 (XRCC1) Arg194Trp, a substitution of Arg to Gln at position 194, has been implicated in the development of colorectal cancer (CRC) in a number of case-control studies with contradictory and inconclusive findings. The current meta-analysis of all currently available publications was conducted to assess the gene susceptibility to CRC and improve our understanding of the CRC pathogenesis. The pooled odds ratio (OR) with corresponding 95 % confidence interval (95 % CI) was calculated by use of fixed-effects model or random-effects model when appropriate. A total of 15 eligible case-control studies with 4,501 cases and 8,038 controls were retrieved after a comprehensive search of the PubMed, Embase, Web of science, and Chinese Biomedicine (CBM) databases up to December 2012. The overall meta-analysis identified a positive but not statistically significant association between the XRCC1 Arg194Trp polymorphism and CRC risk under all genetic contrast models (ORTrp vs. Arg = 1.07, 95 % CI 0.90-1.26, P OR = 0.441; ORTrpTrp vs. ArgArg = 1.28, 95 % CI 0.91-1.81, P OR = 0.163; ORArgTrp vs. ArgArg = 1.00, 95 % CI 0.85-1.19, P OR = 0.956; ORArgTrp + TrpTrp vs. ArgArg = 1.06, 95 % CI 0.90-1.24, P OR = 0.502; ORTrpTrp vs. ArgArg + ArgTrp = 1.11, 95 % CI 0.91-1.34, P OR = 0.306). The genotype TrpTrp carriers among Caucasians were more susceptible to CRC, although lack statistical evidence (ORTrpTrp vs. ArgArg = 2.69, 95 % CI 0.97-7.49, P OR = 0.058; ORTrpTrp vs. ArgArg + ArgTrp = 2.77, 95 % CI 0.99-7.72, P OR = 0.051). Interestingly, the XRCC1 Arg194Trp variant was significantly associated with an increased risk of colon cancer. The present meta-analysis suggests that the XRCC1 Arg194Trp polymorphism may modify the risk for CRC, particularly colon cancer. However, the precise genetic association needs to be further estimated in future studies.

X-ray repair cross-complementing group 1 Arg194Trp polymorphism is associated with increased risk of lung cancer in Chinese Han population

There were many studies performed to assess the association between X-ray repair cross-complementing group 1 (XRCC1) Arg194Trp polymorphism and lung cancer risk in Chinese Han population, but contradictory results were reported. To provide a comprehensive and objective assessment of the association, a meta-analysis of all eligible case-control studies was carried out. After searching the databases and reading the abstracts, 12 case-control studies on the association between XRCC1 Arg194Trp polymorphism and lung cancer risk were finally included into this meta-analysis. Those 12 studies included a total of 4,385 cases and 4,545 controls. XRCC1 Arg194Trp polymorphism was associated with increased risk of lung cancer in Chinese Han population under three main models (allele contrast model, odds ratio (OR) = 1.12, 95 % confidence interval (CI) 1.00-1.26, P = 0.049; homozygote model, OR = 1.27, 95 % CI 1.09-1.48, P = 0.003; recessive model, OR = 1.26, 95 % CI 1.09-1.46, P = 0.003). However, there was no obvious association between XRCC1 Arg194Trp polymorphism and lung cancer risk under the dominant model (OR = 1.06, 95 % CI 0.98-1.16, P = 0.146). Sensitivity analysis suggested the stability and liability of this meta-analysis. Therefore, this meta-analysis suggests that XRCC1 Arg194Trp polymorphism is associated with increased risk of lung cancer in Chinese Han population.

X-Ray Repair Cross-Complementing Group 1(XRCC1) Genetic Polymorphisms and Thyroid Carcinoma Risk: a Meta-Analysis

A number of studies have been conducted to explore the association of XRCC1 polymorphisms with thyroid cancer risk, but the results have been inconsistent. Thus we performed the present meta-analysis to clarify this issue based on all of the evidence available to date. Relevant studies were retrieved by searching PubMed and statistical analysis conducted using Stata software. Nine studies were included in this meta-analysis (1,620 cases and 3,557 controls). There were 6 studies (932 cases and 2,270 controls) of the Arg194Trp polymorphism, 7 studies (1432 cases and 3356 controls) of the Arg280His polymorphism and 9 studies (1,620 cases and 3,557 controls) for the Arg399Gln polymorphism. No association of XRCC1 Arg194Trp, Arg280His and Arg399Gln polymorphism with thyroid cancer risk was observed in the overall analysis. However, subgroup analysis revealed: 1) an elevated risk in aa vs AA analysis (OR=2.03, 95%CI= 1.24-3.31) and recessive genetic model analysis (OR=1.93, 95%CI= 1.20-3.08) in the larger sample size trials for XRCC1 Arg194Trp polymorphism; 2) a decreased thyroid cancer risk on subgroup analysis based on ethnicity in Aa vs AA analysis (OR=0.84, 95%CI= 0.72-0.98) and in a dominant genetic model (OR=0.84, 95%CI= 0.72-0.97) in Caucasian populations for the XRCC1 Arg399Gln polymorphism; 3) a decreased thyroid cancer risk on subgroup analysis based on design type in Aa vs AA analysis (OR=0.72, 95% CI= 0.54-0.97) among the PCC trials for the Arg399Gln polymorphism. Our results suggest that the XRCC1 Arg399Gln polymorphism may be associated with decreased thyroid cancer risk among Caucasians and XRCC1 Arg194Trp may be associated with a tendency for increased thyroid cancer risk in the two larger sample size trials.

DNA Repair Gene X-Ray Repair Cross Complementing Group 1 Arg194Trp Polymorphism on the Risk of Lung Cancer: A Meta-Analysis on 22 Studies

DNA repair gene X-ray repair cross complementing group 1 (XRCC1) Arg194Trp polymorphism has been investigated widely on lung cancer risk. However, the results are inconclusive. To derive a more precise estimation of the relationship between XRCC1 Arg194Trp polymorphism and lung cancer risk, we performed this meta-analysis. An electronic search of the database PubMed, Embase, and Chinese National Knowledge Infrastructure was performed. The odds ratio (OR) was pooled by STATA 10.1. Subgroup analyses by ethnicity, gender, smoking, and histologic types of lung cancer were performed. Twenty-two studies including 7515 cases and 9560 controls were identified ultimately. The pooled OR for total population showed that homozygous Trp/Trp variant genotype could increase lung cancer risk compared with the homozygous wild Arg/Arg genotype (OR = 1.22, 95% confidence interval [CI] = 1.04-1.44, p = 0.01); however, heterozygote Arg/Trp variant genotype could decrease lung cancer risk (OR = 0.91, 95% CI = 0.85-0.99, p = 0.02). Subgroup analyses by ethnicity confirmed the result that homozygous Trp/Trp variant genotype increased lung cancer risk in Asians (OR = 1.19, 95% CI = 1.01-1.41, p = 0.04) but not in whites. It was interesting to find that both the heterozygote Arg/Trp and the combined Trp/Trp + Arg/Trp variant genotypes could decrease the risk of lung cancer in whites (OR = 0.83, 95% CI = 0.72-0.96, p = 0.01; OR = 0.85, 95% CI = 0.74-0.98, p = 0.03, respectively) but not in Asians. Subgroup analyses by gender, smoking, and histologic types of lung cancer did not indicate any significant difference between cases and controls, excepted for male population, which carried heterozygote Arg/Trp variant genotype that could decrease lung cancer risk (OR = 0.54, 95% CI = 0.31-0.95, p = 0.03). Homozygous Trp/Trp variant genotype of XRCC1 Arg194Trp polymorphism could increase lung cancer risk in total population, especially in Asians. However, the heterozygote Arg/Trp variant genotype might decrease the risk of lung cancer, especially in whites.

Association of polymorphism of DNA repair gene XRCC1 with sporadic late-onset Alzheimer's disease and age of onset in elderly Han Chinese

Alzheimer's disease (AD) is characterized by the presence of β-amyloid plaques, neurofibrillary tangles and extensive neuronal loss. There is evidence indicating that the increased DNA damages may contribute to neuronal loss in AD. Recently, it has been shown that the capacity of some types of DNA repair is impaired in the neurons of AD patients. A functional polymorphism (Arg194Trp) of X-ray repair cross-complementing group 1 ( XRCC1) gene may be associated with the repair efficiency of DNA damage which may have a role in AD. Therefore, XRCC1 Arg194Trp polymorphism may be a good candidate for genetic risk analysis in AD. A case–control study from Turkey found that XRCC1 194Trp was associated with late-onset AD (LOAD). In order to determine whether the XRCC1 gene Arg194Trp polymorphism contributes to the risk for LOAD in elderly Han Chinese, we have investigated it in 212 sporadic LOAD patients and 203 healthy controls from Chinese. No significantly increased risk of LOAD in the carriers of XRCC1 194Trp allele (OR = 1.04, 95% CI 0.70–1.52, P = 0.860) was observed. As expected, Apolipoprotein ( APOE) ε4 allele significantly increased the risk of LOAD (OR = 2.95, 95% CI 1.90–4.58, P < 0.001), while APOE ε2 allele significantly decreased the risk of LOAD (OR = 0.13, 95% CI 0.08–0.24, P < 0.001). After stratifying by APOE ε4 status, no increased LOAD risks associated with the XRCC1 194Trp allele carriers were observed. Our findings suggest that it is unlikely that the XRCC1 Arg194Trp polymorphism plays a major role in the pathogenesis of LOAD in elderly Han Chinese and does not support the previous findings that 194Trp allele confers an increased risk for LOAD.

XRCC1 Arg194Trp polymorphism and risk of chronic obstructive pulmonary disease

The DNA damage, caused by cigarette smoking, can cause airway cell apoptosis and death, which may be associated with the development of chronic obstructive pulmonary disease (COPD). However, just 20%-30% smokers develop COPD, which suggests that different degrees of DNA repair cause different outcomes in smokers. X-ray repair cross-complementing group 1 (XRCC1), a base excision repair protein, has multiple roles in repairing ROS-mediated, basal DNA damage and single-strand DNA breaks. The present study investigated the association between polymorphism in XRCC1 (Arg399Gln) and susceptibility of COPD. A total of 201 COPD cases and 309 controls were recruited and frequency-matched on age and sex. XRCC1 genotype was determined by PCR-restriction fragment length polymorphism analysis. Overall, compared with those with the XRCC1 Arg/Arg genotype, the risk for COPD had no significant difference among individuals with Trp/Trp genotype. However, after stratifying by smoking status, in former smokers, compared with those with the XRCC1 Arg/Arg genotype, the risk for COPD was significantly reduced among individuals with Trp/Trp genotype (adjusted OR=0.22, 95% CI 0.06-0.85, P=0.028); after stratifying by smoking exposure, in light smokers, compared with those with the XRCC1 Arg/Arg genotype, the risk for COPD was significantly reduced among individuals with Arg/Trp genotype and Trp/Trp genotype (adjusted OR=0.39, 95% CI 0.16-0.94, P=0.036; 0.24, 95% CI 0.07-0.79, P=0.019, respectively). In conclusion, XRCC1 Arg194Trp genotype is associated with a reduced risk of developing COPD among former and light smokers.

The Arg194Trp Polymorphism in the X-ray Repair Cross-Complementing Group 1 Gene as a Potential Risk Factor of Oral Cancer: A Meta-Analysis

Polymorphisms in the X-ray repair cross-complementing group 1 (XRCC1) gene have been reported as a potential risk factor for the development of oral cancer; however, the overall results are still controversial. In the present study, we therefore performed a meta-analysis of eight case-control studies that examined the association of oral cancer with XRCC1 gene polymorphisms in different populations, including codon 194 (Arg-Trp), 280 (Arg-His) and 399 (Arg-Gln), based on the data identified in Medline of up to June 2008. Literature-based searching was conducted to gather data and both fixed-effects and random-effects model were used to pool the odds ratio (OR). Publication bias and between-study heterogeneity were also evaluated. The eligible studies included 1,326 cases and 3,130 controls. The OR of various comparisons showed that the oral cancer risk was not associated with the selected three XRCC1 polymorphisms (P > 0.05). However, after stratification, significant association was found between the XRCC1 Arg194Trp polymorphism and oral cancer risk among Asians, showing an OR of 1.347 (95% confidence interval (CI): 1.000, 1.814) for allele comparison, 1.378 (95% CI: 1.070, 1.775) for TT homozygotes versus CC homozygotes, and 1.420 (95% CI: 1.041, 1.936) for comparison under the dominant model. Publication bias was not shown around the studies; however, ORs among these three polymorphisms all yielded significant between-study heterogeneity (P < 0.05) and a part of the heterogeneity was from ethnic differences. We suggest that the Arg194Trp polymorphism in the XRCC1 gene may be a biomarker of oral cancer susceptibility among Asian population.