Meta-Analysis of the Relationship between XRCC1-Arg399Gln and Arg280His Polymorphisms and the Risk of Prostate Cancer.
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ABSTRACT:
SUBMITTER: Yan J
PROVIDER: S-EPMC4415422 | biostudies-other | 2015
REPOSITORIES: biostudies-other
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Project description:BackgroundThe previous published data on the association between the X-ray repair cross-conplementation group 1 (XRCC1) polymorphisms and thyroid cancer risk remained controversial. Hence, we performed a meta-analysis on all available studies that provided 1729 cases and 3774 controls (from 11 studies) for XRCC1 Arg399Gln, 1040 cases and 2487 controls for Arg194Trp (from 7 studies), and 1432 cases and 3356 controls for Arg280His (from 8 studies).Methodology/principal findingsPubMed, CNKI, and EMBASE database were searched to identify relevant studies. Overall, no significant association was found between XRCC1 Arg399Gln (recessive model: OR = 0.95, 95% CI = 0.77-1.15; dominant model: OR = 0.89, 95% CI = 0.75-1.05; homozygote model: OR = 0.92, 95% CI = 0.69-1.23; Heterozygote model: OR = 0.91, 95% CI = 0.80-1.03; additive model: OR = 0.93, 95% CI = 0.81-1.07), Arg194Trp (recessive model: OR = 1.41, 95% CI = 0.62-3.23; dominant model: OR = 1.01, 95% CI = 0.77-1.34; homozygote model: OR = 1.42, 95% CI = 0.55-3.67; Heterozygote model: OR = 1.03, 95% CI = 0.85-1.26; additive model: OR = 1.08, 95% CI = 0.81-1.42), and Arg280His (recessive model: OR = 1.08, 95% CI = 0.56-2.10; dominant model: OR = 1.01, 95% CI = 0.84-1.22; homozygote model: OR = 1.00, 95% CI = 0.51-1.96; Heterozygote model: OR = 1.04, 95% CI =0.75-1.42; additive model: OR = 1.03, 95% CI = 0.86-1.23) and thyroid cancer risk when all the eligible studies were pooled into the meta-analysis. In the further stratified and sensitivity analyses, significant association was still not found in these three genetic polymorphisms.Conclusions/significanceIn summary, this meta-analysis indicates that XRCC1 Arg399Gln, Arg280His, and Arg194Trp are not associated with thyroid cancer.
| S-EPMC4161346 | biostudies-literature
Project description:BackgroundThe prevalence of lung cancer in China will be the world's highest if allowed to proceed uncurbed. To unravel its genetic underpinnings, we sought to investigate the association of three well-characterized nonsynonymous polymorphisms in XRCC1 (Arg194Trp and Arg399Gln) and XRCC3 (Thr241Met) genes with lung cancer risk in northeastern Chinese.Methodology/principal findingsThis study was hospital-based in design, encompassing 684 patients with lung cancer and 604 cancer-free controls. Genotyping was performed using the PCR-LDR (ligase detection reactions) method. Data were analyzed by R language and multifactor dimensionality reduction (MDR) software. Single-locus analysis identified significance in genotype distributions of polymorphism Arg194Trp (P = 0.002) and Arg399Gln (P = 0.017), and in allele distributions of Thr241Met (P = 0.005). Carriers of 399Gln/Gln genotype conferred a 147% increased risk relative to the non-carriers (odds ratio (OR): 2.47; 95% confidence interval (95% CI): 1.48-4.13; P<0.001). For Thr241Met, significance persisted under allelic (OR = 1.63; 95% CI: 1.14-2.33; P = 0.005), additive (OR = 1.64; 95% CI: 1.16-2.32; P = 0.005) and dominant (OR = 1.67; 95% CI: 1.17-2.38; P = 0.004) models. However, common allele combinations were comparable in frequency between patients and controls. In interaction analysis, the overall best MDR model included Arg399Gln and Thr241Met polymorphisms, with a maximal testing accuracy of 63.18% and a maximal cross-validation consistency of 10 out of 10 (P = 0.0175).ConclusionsOur study significantly demonstrated an independent and synergistic contribution of XRCC1 Arg399Gln and XRCC3 Thr241Met polymorphisms to lung cancer susceptibility in northeastern Chinese.
| S-EPMC3568083 | biostudies-literature
Project description:Many studies have reported the association of X-ray repair cross-complementing group 1 (XRCC1) Arg399Gln, Arg194Trp, Arg280His, -77T>C, and X-ray repair cross-complementing group 3 (XRCC3) T241M polymorphisms with lung cancer risk, but the results remained controversial. Hence, we performed a meta-analysis to investigate the association between lung cancer risk and XRCC1 Arg399Gln (14,156 cases and 16,667 controls from 41 studies), Arg194Trp (7,426 cases and 9,603 controls from 23 studies), Arg280His (6,211 cases and 6,763 controls from 16 studies), -77T>C (2,487 cases and 2,576 controls from 5 studies), and XRCC3 T241M (8,560 cases and 11,557 controls from 19 studies) in different inheritance models. We found that -77T>C polymorphism was associated with increased lung cancer risk (dominant model: odds ration [OR]?=?1.45, 95% confidence interval [CI]?=?1.27-1.66, recessive model: OR?=?1.73, 95% CI?=?1.14-2.62, additive model: OR?=?1.91, 95% CI?=?1.24-1.94) when all the eligible studies were pooled into the meta-analysis. In the stratified and sensitive analyses, significantly decreased lung cancer risk was observed in overall analysis (dominant model: OR?=?0.83, 95% CI?=?0.78-0.89; recessive model: OR?=?0.90, 95% CI?=?0.81-1.00; additive model: OR?=?0.82, 95% CI?=?0.74-0.92), Caucasians (dominant model: OR?=?0.82, 95% CI?=?0.76-0.87; recessive model: OR?=?0.89, 95% CI?=?0.80-0.99; additive model: OR?=?0.81, 95% CI?=?0.73-0.91), and hospital-based controls (dominant model: OR?=?0.81, 95% CI?=?0.76-0.88; recessive model: OR?=?0.89, 95% CI?=?0.79-1.00; additive model: OR?=?0.80, 95% CI?=?0.71-0.90) for XRCC3 T241M. In conclusion, this meta-analysis indicates that XRCC1 -77T>C shows an increased lung cancer risk and XRCC3 T241M polymorphism is associated with decreased lung cancer risk, especially in Caucasians.
| S-EPMC3753326 | biostudies-literature
Project description:The present meta-analysis was intended to explore the relationship between the X-ray repair cross complementing 1 (XRCC1) polymorphisms (Arg194Trp, Arg280His and Arg399Gln) and cervical cancer risk. Several electronic databases were searched systematically and bibliographies of relevant papers were identified carefully. Then, a meta-analysis was performed based on eligible studies in various genetic models. Pooled odds ratios (OR) with 95% confidence intervals (95% CI) were employed to evaluate the strength of associations between the XRCC1 polymorphisms and cervical cancer risk. Additionally, heterogeneity analysis and sensitivity analysis were done if necessary. Totally, 11 articles involving 2092 cases and 2803 controls were included. Taken together, there was no obvious association between the Arg194Trp or Arg280His polymorphism and cervical cancer risk. Considering the great heterogeneity, subgroup analysis was done, but the pooled result remained stable. Nevertheless, the association between the Arg399Gln polymorphism and cervical cancer risk showed distinct statistic significance in the allele model, dominant model, homozygous model and heterozygous model. In view of the exiting heterogeneity, we did subgroup analysis stratified by ethnicity, resulting in the fact that the Arg399Gln polymorphism was related to the decreased risk of cervical cancer. The Begg's test and Egger's test were used to find no publication bias. To conclude, the current meta-analysis indicated that the XRCC1 Arg399Gln polymorphism decreased the risk of cervical cancer, while the Arg194Trp and Arg280His polymorphisms were not associated with cervical caner risk. Certainly, a well-designed large-scale multicenter study is warranted to confirm the finding.
| S-EPMC5356796 | biostudies-literature
Project description: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.
| S-EPMC7440050 | biostudies-literature
Project description:BACKGROUND AND OBJECTIVE: The X-ray repair cross-complementing group 1 (XRCC1) protein plays a crucial role in base excision repair (BER) pathway by acting as a scaffold for other BER enzymes. Variants in the XRCC1 gene might alter protein structure or function or create alternatively spliced proteins which may influence BER efficiency and hence affect individual susceptibility to bladder cancer. Recent epidemiological studies have shown inconsistent associations between these polymorphisms and bladder cancer. To clarify the situation, a comprehensive meta-analysis of all available studies was performed in this study. METHODS: PubMed, EMBASE, and Chinese Biomedical Literature database (CBM) databases have been systematically searched to identify all relevant studies for the period up to February 2013. Data were abstracted independently by two reviewers and Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Subgroup analyses were performed mainly by ethnicity and smoking status. RESULTS: A total of 26 case-control studies, including 24 studies for R399Q polymorphism, 15 studies for R194W polymorphism, and 7 studies for R280H polymorphism met the inclusion criteria and were selected. With respect to R399Q polymorphism, significantly decreased bladder cancer risk was found among smokers (AA vs. GG: OR=0.693, 95%CI= 0.515-0.932, P=0.015 and recessive model AA vs. GA+GG: OR=0.680, 95%CI= 0.515-0.898, P=0.007, respectively). With respect to R194W and R280H polymorphism, significantly increased bladder cancer risk were observed among Asians (TT+CT vs. CC:OR = 1.327, 95% CI 1.086-1.622, P=0.006 for R194W, and AA+GA vs. GG: OR=2.094, 95% CI 1.211-3.621, P=0.008 for R280H, respectively). CONCLUSIONS: This meta-analysis suggests that the XRCC1 R399Q polymorphism may play a protective role against bladder cancer among smokers. However, the XRCC1 R194W and R280H polymorphisms were both associated with increased bladder cancer risk among Asians. Further studies with larger sample sizes are needed to validate our finds.
| S-EPMC3767803 | biostudies-literature
Project description:BackgroundX-ray repair cross-complementing group 1 (XRCC1) is one of the DNA repair genes encoding a scaffolding protein that participate in base excision repair (BER) pathway. However, studies on the association between polymorphisms in this gene and glioma have yielded conflicting results. This meta-analysis was performed to derive a more precise estimation between XRCC1 polymorphisms (Arg399Gln, Arg194Trp, and Arg280His) and glioma risk.MethodsData were collected from several electronic databases, with the last search up to November 28, 2012. Meta-analysis was performed by critically reviewing 9 studies for Arg399Gln polymorphism (3146 cases and 4296 controls), 4 studies for Arg194Trp polymorphism (2557 cases and 4347 controls), and 4 studies for Arg280His polymorphism (1936 cases and 2895 controls). All of the statistical analyses were performed using the software programs STATA (version 11.0).ResultsThe combined results showed that Arg399Gln polymorphism was significantly associated with glioma risk (Gln/Gln versus Arg/Arg: OR = 1.52, 95% CI = 1.03-2.23; recessive model: OR = 1.32, 95% CI = 1.01-1.73; additive model: OR = 1.21, 95% CI = 1.00-1.47), whereas Arg194Trp/Arg280His polymorphisms were all not significantly associated with glioma risk. As for ethnicity, Arg399Gln polymorphism was associated with increased risk of glioma among Asians (Gln/Gln versus Arg/Arg: OR = 1.78, 95% CI = 1.29-2.47; Arg/Gln versus Arg/Arg: OR = 1.28, 95% CI = 1.05-1.56; recessive model: OR = 1.59, 95% CI = 1.16-2.17; dominant model: OR = 1.36, 95% CI = 1.13-1.65; additive model: OR = 1.32, 95% CI = 1.15-1.52), but not among Caucasians. Stratified analyses by histological subtype indicated that the Gln allele of Arg399Gln polymorphism showed borderline association with the risk of glioblastoma among Caucasians. However, no evidence was observed in subgroup analyses for Arg194Trp/Arg280His polymorphisms.ConclusionsOur meta-analysis suggested that Arg399Gln polymorphism was associated with increased risk of glioma among Asians and borderline increased risk for glioblastoma among Caucasians, whereas Arg194Trp/Arg280His polymorphisms might have no influence on the susceptibility of glioma in different ethnicities.
| S-EPMC3559473 | biostudies-literature
Project description:The relationship between XRCC1 polymorphisms and bladder cancer has been widely studied. Here, our meta-analysis was conducted to evaluate the correlations between common genetic polymorphisms in XRCC1 and susceptibility to bladder cancer. In order to derive a more precise estimation of the association, 27 clinical case-control studies (which met all the inclusion criteria) were included in this meta-analysis. A total of 8,539 cancer cases and 10,750 controls were involved in this meta-analysis. Overall, no significant association was detected in allelic model (A allele vs T allele odds ratio [OR] =0.87, 95% confidence interval [CI], 0.71-1.06), homozygote comparison (AA vs GG OR =1.12, 95% CI, 0.68-1.85), heterozygote comparison (AT vs TT OR =1.01, 95% CI, 0.81-1.26), dominant model (AA + AG vs GG OR =0.93, 95% CI, 0.85-1.02), and recessive model (AA vs AG + GG OR =1.01, 95% CI, 0.88-1.15), but a moderately significant association was found for AG vs GG (OR =0.241, 95% CI =0.17-0.35). Subgroup analysis based on ethnicity. Ethnicity analysis suggested that genetic polymorphisms in XRCC1 were not correlated with increased bladder cancer risk among Asians (all P>0.05). Therefore, we concluded that XRCC1 genetic polymorphism may not contribute to bladder cancer susceptibility in the present meta-analysis, and further well-designed studies with a large sample size are warranted to validate our conclusion.
| S-EPMC4734791 | biostudies-literature
Project description:ObjectiveNon-melanoma skin cancer (NMSC) is the most common malignancy with annually rising incidence. The aim of this study was to estimate the association between three coding polymorphisms (Arg399Gln, Arg194Trp, and Arg280His) of the DNA repair gene X-ray repair cross-complementing group 1 (XRCC1) and NMSC susceptibility.MethodsOnline databases were searched to retrieve case-control studies published between January 2000 and November 2016. Pooled odds ratio (OR) and 95% confidence interval (CI) were employed to assess the strength of association. Overall, 10 relevant studies were finally included for analysis, including 3,143 NMSC patients and 3,540 controls. For each polymorphism of XRCC1 gene, there were 3,050 cases and 3,463 controls for Arg399Gln, 914 cases and 1,182 controls for Arg194Trp, and 279 cases and 413 controls for Arg280His.ResultsOur results showed that these three polymorphisms in the XRCC1 coding region were not associated with increased risk of NMSC in the total studied population. However, subgroup analysis by ethnicities demonstrated that Gln/Arg genotype of Arg399Gln polymorphism was associated with increased risk of NMSC under the heterogeneous model in Asian populations (Gln/Arg vs Arg/Arg: OR =1.39, 95% CI =1.04-1.87, P=0.03); subgroup analysis by tumor types showed that Trp/Trp genotype of Arg194Trp was positively associated with decreased cancer risk in squamous-cell skin cancer (SCC) type under the homogeneous model (Trp/Trp vs Arg/Arg: OR =0.38, 95% CI =0.16-0.92, P=0.03).ConclusionOur results suggested that Arg399Gln variant of XRCC1 gene might be a risk factor for NMSC in Asian populations, and Arg194Trp variant of XRCC1 gene might be a protective factor for patients with SCC. In addition, future case-control studies are still needed to further evaluate the effect of XRCC1 polymorphisms in NMSC risk.
| S-EPMC5518917 | biostudies-literature
Project description:Conflicting results have been obtained regarding the association between X-ray repair cross complementation group 1 (XRCC1) and susceptibility to hepatocellular carcinoma (HCC). In this study, associations between HCC and three polymorphisms (Arg194Trp, Arg280His, and Arg399Gln) were evaluated using a meta-analysis approach. PubMed, Web of Science, Cochrane Library, the Chinese National Knowledge Infrastructure, and the Wanfang standard database were systematically searched to identify all relevant case-control studies published through March 2018. A total of 32 case-control studies, including 13 that evaluated Arg194Trp, 14 that evaluated Arg280His, and 26 that evaluated Arg399Gln, were analyzed. In the entire study population, XRCC1 Arg399Gln was significantly associated not only with overall risk of HCC (homozygous model, OR = 1.61, 95% CI: 1.40-1.85, P < 0.05; recessive model, OR = 1.40, 95% CI: 1.23-1.59, P < 0.05) but also with the risk of HCC in Chinese patients (homozygous model, OR = 1.78, 95% CI: 1.53-2.08, P < 0.05; recessive model, OR = 1.47, 95% CI: 1.27-1.70, P < 0.05). Limiting the analysis to studies demonstrating Hardy-Weinberg equilibrium (HWE), the results were consistent and robust. Similarly, a significant association between XRCC1 Arg399Gln and HCC risk was found in healthy controls in the general population but not in hospital controls. Trial sequential analysis (TSA), false-positive report probabilities (FPRP), and combined genotype analysis revealed that XRCC1 Arg399Gln is mainly associated with susceptibility to liver cancer. However, there was no association between Arg194Trp or Arg280His and the risk of HCC. These results, indicating that the Arg399Gln polymorphism of XRCC1 is associated with the risk of HCC in the Chinese population, provide a basis for the development of improved detection and treatment approaches.
| S-EPMC6226104 | biostudies-literature