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ERCC2 polymorphisms and radiation-induced adverse effects on normal tissue: systematic review with meta-analysis and trial sequential analysis.

ABSTRACT: The relationship between ERCC2 polymorphisms and the risk of radiotoxicity remains inconclusive. The aim of our study is to systematically evaluate the association between ERCC2 polymorphisms and the risk of radiotoxicity.Publications were identified through a search of the PubMed and Web of Science databases up to August 15, 2015. The pooled odds ratios (ORs) with corresponding 95 % confidence intervals (CIs) were calculated to evaluate the association between ERCC2 polymorphisms and radiotoxicity. Trial sequential analysis (TSA) and power calculation were performed to evaluate the type 1 and type 2 errors.Eleven studies involving 2584 patients were ultimately included in this meta-analysis. Conventional meta-analysis identified a significant association between ERCC2 rs13181 polymorphism and radiotoxicity (OR?=?0.71, 95 % CI: 0.55-0.93, P?=?0.01), but this association failed to get the confirmation of TSA.The minor allele of rs13181 polymorphism may confer a protect effect against radiotoxicity. To confirm this correlation at the level of OR?=?0.71, an overall information size of approximate 2800 patients were needed.

SUBMITTER: Song YZ

PROVIDER: S-EPMC4665885 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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ERCC2 polymorphisms and radiation-induced adverse effects on normal tissue: systematic review with meta-analysis and trial sequential analysis.

Song Yu-Zhe YZ Duan Mei-Na MN Zhang Yu-Yu YY Shi Wei-Yan WY Xia Cheng-Cheng CC Dong Li-Hua LH

Radiation oncology (London, England) 20151201

<h4>Background</h4>The relationship between ERCC2 polymorphisms and the risk of radiotoxicity remains inconclusive. The aim of our study is to systematically evaluate the association between ERCC2 polymorphisms and the risk of radiotoxicity.<h4>Methods</h4>Publications were identified through a search of the PubMed and Web of Science databases up to August 15, 2015. The pooled odds ratios (ORs) with corresponding 95 % confidence intervals (CIs) were calculated to evaluate the association between ...[more]

PMID: 26627042

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Project description:Background and Objective: Excision repair cross complementing (ERCC) group genes play important roles in the nucleotide excision repair (NER) way, which can effectively remove bulky lesions and reduce UV-caused DNA damage by environmental chemicals. Polymorphisms in ERCCs were thought to be related to prostate cancer (PCa) risk. However, it has been unclear whether this relationship is consistent. This study aimed to obtain the overall profile regarding the associations between ERCCs polymorphisms and PCa risk. Materials and Methods: We identified relevant studies by a systematic search of PubMed, Medline, Embase, Google Scholar databases, Web of Science and Wanfang databases up to April 8, 2018. Odds ratios (ORs) with 95% confidential intervals (95%CIs) were conducted to evaluate the associations. All the statistical analyses were conducted basing on STATA 12.0 software. Results: Finally, a total of 29 previous studies published in 17 publications were included for four polymorphisms in two DNA repair genes (ERCC2-rs1799793, ERCC2-rs238406, ERCC2-rs13181 and ERCC5-rs17655). Overall, we observed no significant connection between these four polymorphisms and PCa risk. However, after stratifying the studies by ethnicity, ERCC2-rs1799793 polymorphism was associated with an increased risk of PCa in Asian patients and the relationship was subsequently validated with the allelic model, the homozygous model and the recessive model when extracting the data of Asian patients for specific analyses (B vs. A: OR = 1.537, 95%CI: 1.240-1.906, PA< 0.001; BB vs. AA: OR = 2.089, 95%CI: 1.388-3.145, PA< 0.001 and BB vs. BA + AA: OR = 1.929, 95%CI: 1.313-2.835, PA= 0.020). Furthermore, subgroup analyses were also conducted by Hardy-Weinberg Equilibrium (HWE) and source of control, negative results were identified for ERCC2-rs238406, ERCC2-rs13181 and ERCC5-rs17655 polymorphisms (PA> 0.050). Conclusion: To sum up, our work demonstrated that ERCC2-rs1799793 polymorphism is positively associated with PCa risk in Asian population. Further larger-scale studies with subjects of the same ethnicity and biological characteristics are required to verify these findings.

Project description:BackgroundPotential xeroderma pigmentosum group D (XPD), also called excision repair cross-complimentary group two (ERCC2), Lys751Gln and Asp312Asn polymorphisms have been implicated in gastric cancer risk among different ethnicities.MethodsWe aimed to explore the effect of XPD Lys751Gln and Asp312Asn polymorphisms on the susceptibility to gastric cancer among different ethnicities through a systematic review and meta-analysis. Each initially included article was scored for quality appraisal. Desirable data were extracted and registered into databases. 13 studies were ultimately eligible for the meta-analysis of Lys751Gln polymorphism and 9 studies for the meta-analysis of Asp312Asn polymorphism. We adopted the most probably appropriate genetic model (recessive model) for both Lys751Gln and Asp312Asn polymorphisms. Potential sources of heterogeneity were sought out via subgroup and sensitivity analyses, and publication biases were estimated.ResultsStatistically significant findings were apparently noted in Asians but not in Caucasians for both XPD Lys751Gln and XPD Asp312Asn polymorphisms. A statistically significant finding could be seen in noncardia-type gastric cancer for XPD Lys751Gln polymorphism. A statistically significant finding could also be seen in high quality subgroup, small-and-moderate sample size subgroup, articles published after 2007, or PCR-RFLP genotyping subgroup for XPD Asp312Asn polymorphism.ConclusionsOur meta-analysis indicates that XPD Gln751Gln (CC) genotype and Asn312Asn (AA) genotype may seem to be more susceptible to gastric cancer in Asian populations but not in Caucasian populations, suggesting that the two genotypes may be important biomarkers of gastric cancer susceptibility for Asian populations, the assumption that needs to be further confirmed in well-designed studies among different ethnicities. Gln751Gln (CC) genotype may also be associated with noncardia-type gastric cancer risk, which should also be confirmed among different ethnicities in the future.

Project description:ObjectivesTo comprehensively evaluate the association of ERCC1 C8092A and ERCC2 Lys751Gln polymorphisms with the risk of glioma.MethodsPotential studies were searched and selected through the Pubmed/MEDLINE, EMBASE, the China National Knowledge Infrastructure (CNKI) platforms, WanFang and VIP database up to June 2013. Two investigators independently reviewed full text and included studies met inclusion criteria. Combined odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated in a fixed-effects model or a random-effects model according to results of heterogeneity test. All analyses were performed by Revman 5.2 and Stata 10.0 software.ResultsA total of 10 studies were included in our meta-analysis, including 3,580 glioma patients and 4,728 controls. Overall, ERCC1 C8092A polymorphism was associated with the risk of glioma (AA vs. CC: OR = 1.29, 95%CI: 1.07-1.55, P = 0.01; recessive model: OR = 1.29; 95% CI: 1.07-1.55, P = 0.01). When stratified by ethnicity, significant association was only observed in the Chinese population (AA vs. CC: OR = 1.37, 95%CI: 1.03-1.81, P = 0.03; recessive model: OR = 1.34; 95% CI: 1.02-1.75, P = 0.04). For ERCC2 Lys751Gln polymorphism, no significant association was found between ERCC2 Lys751Gln polymorphism and the risk of glioma in different genetic models. A significant association of ERCC2 Lys751Gln polymorphism with the risk of glioma was identified in the Caucasian population under recessive model (OR = 0.87; 95% CI: 0.78-0.98, P = 0.02), but not in the Chinese population.ConclusionThis meta-analysis suggested that the AA genotype of ERCC1 C8092A polymorphism might increase the susceptibility of glioma in the Chinese population. And the TT genotype of ERCC2 Lys751Gln polymorphism may decrease the risk of glioma in the Caucasian population. But the small number of studies and moderate methodological quality require cautious interpretation of the study results.

Project description:Previous studies have yielded controversial results related to the contribution of interleukin 10 (IL-10) gene polymorphisms (IL-10 -592C/A, IL-10 -1082G/A, and IL-10 -819C/T) in the progression of cardiovascular disease (CVD). Thus, we performed a meta-analysis to summarize this situation.Eligible studies were retrieved by searching PubMed, Embase, Web of Science, and Cochrane Library with the last search up to July 7, 2015. Data were pooled by odds ratios (ORs) and their 95% confidence intervals (CIs). False-positive report probability (FPRP) analysis was conducted for all significant findings. Genotype-based mRNA expression analysis was also performed using data from 270 individuals with different ethnicities.Finally, 19 studies for IL-10 -592C/A polymorphism (7284 cases and 7469 controls), 21 studies for IL-10 -1082G/A polymorphism (8263 cases and 5765 controls), and 12 studies for IL-10 -819C/T polymorphism (4502 cases and 3190 controls) were included in the meta-analyses. With respect to IL-10 -819C/T polymorphism, statistically significant decreased CVD risk was found when all studies were pooled into the meta-analysis (T vs C: OR = 0.91, 95% CI = 0.84-0.98; TT + TC vs CC: OR = 0.90, 95% CI = 0.81-1.00). Subgroup analyses stratified by disease subtype suggested the -819C/T polymorphism was significantly associated with a decreased CAD risk (T vs C: OR = 0.90, 95% CI = 0.83-0.97; TT vs CC: OR = 0.81, 95% CI = 0.66-1.00; TT vs TC + CC: OR = 0.82, 95% CI = 0.69-0.98; TT + TC vs CC: OR = 0.89, 95% CI = 0.80-0.99), which was noteworthy finding as evaluated by FPRP. However, with regard to IL-10 -592C/A and IL-10 -1082G/A polymorphisms, no significant association with CVD risk was observed in the overall and subgroup analyses.In conventional meta-analyses, the results suggested that IL-10 -819C/T polymorphism was associated with decreased risk of CVD, especially CAD outcome, whereas IL-10 -592C/A and IL-10 -1082G/A polymorphisms might have no influence on the susceptibility of CVD. However, trial sequential analysis does not allow us to draw any solid conclusion for the association between IL-10 -592C/A or IL-10 -1082G/A polymorphism and CVD risk. Further large and well-designed studies are still needed.

Project description:PurposeX-Ray Repair Cross Complementing 1 (XRCC1) functioning in the base excision repair pathway plays an important role in the repair of DNA single-strand breaks caused by ionizing radiation. The relationship between XRCC1 polymorphisms and the risk of radiation-induced side effects on normal tissues remains controversial. Therefore, we performed a comprehensive meta-analysis to elucidate these associations.Materials and methodsA systematic literature search was carried out in PubMed, Medline (Ovid), Embase, Web of Science, Cochrane database, and the references of relevant studies. The pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were calculated to evaluate the strength of the association.ResultsA total of 40 studies including 6,682 patients were eventually identified in this meta-analysis. Pooled results suggested that rs25487 Arg399Gln polymorphism significantly increased the risk of acute radiation-induced side effects (OR=1.29, 95% CI: 1.10-1.52, P=0.002), especially acute mucositis (OR=1.91, 95% CI: 1.17-3.11, P=0.01) and acute gastrointestinal and genitourinary toxicity (OR=1.49, 95% CI: 1.04-2.11, P=0.03). Furthermore, patients who received head and neck irradiation with rs25487 Arg399Gln polymorphism were more likely to experience radiotherapy (RT)-induced side effects (OR=1.46, 95% CI: 1.12-1.90, P=0.005). However, no statistically significant correlations were identified between rs25487 polymorphism and any late side effects and other irradiation areas. Likewise, no significant associations were detected between rs25489, rs1799782, or rs3213245 polymorphism and RT-induced toxicity.ConclusionOur meta-analysis demonstrated that XRCC1 rs25487 Arg399Gln polymorphism had a significant predictive value and might predict a risk of severely acute RT-induced adverse effects, especially in acute mucositis and acute gastrointestinal and genitourinary toxicity, or in patients with head and neck irradiation. However, large-scale and well-designed studies are required to further evaluate the predictive value of XRCC1 variations on radiation-induced side effects in order to identify radiosensitive patients and predict radiotoxicity.

Dataset Information

ERCC2 polymorphisms and radiation-induced adverse effects on normal tissue: systematic review with meta-analysis and trial sequential analysis.

Publications

ERCC2 polymorphisms and radiation-induced adverse effects on normal tissue: systematic review with meta-analysis and trial sequential analysis.

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