Dataset Information

Association between polymorphisms in DNA repair gene XRCC1 and non-melanoma skin cancer risk: a meta-analysis.

ABSTRACT: OBJECTIVE:Non-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. METHODS:Online 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. RESULTS:Our 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). CONCLUSION:Our 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.

SUBMITTER: Wang L

PROVIDER: S-EPMC5518917 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Association between polymorphisms in DNA repair gene <i>XRCC1</i> and non-melanoma skin cancer risk: a meta-analysis.

Wang Lei L Xu Jia J Duan Baoxue B

OncoTargets and therapy 20170713

<h4>Objective</h4>Non-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.<h4>Methods</h4>Online databases were searched to retrieve case-control studies published between January 2000 and November 2016. Pooled odds ratio (OR) and 95% conf ...[more]

PMID: 28761356

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Project description:Background and objectiveThe 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.MethodsPubMed, 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.ResultsA 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).ConclusionsThis 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.

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.

Dataset Information

Association between polymorphisms in DNA repair gene XRCC1 and non-melanoma skin cancer risk: a meta-analysis.

Publications

Association between polymorphisms in DNA repair gene <i>XRCC1</i> and non-melanoma skin cancer risk: a meta-analysis.

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