XRCC1 Arg399Gln基因多态性与中国人群肝细胞癌易感性的Meta分析

目的 探讨XRCC1 Arg399Gln基因多态性与肝细胞癌（HCC）易感性的关系。方法 计算机检索PubMed、中国生物医学文献（CBM）、中国知网、万方及维普等数据库,收集有关XRCC1 Arg399Gln基因多态性与HCC易感性关系的病例对照研究,提取纳入文献的相关数据进行Meta分析,以病例组与对照组XRCC1 Arg399Gln各种基因模型的比值比（OR）为效应指标,发表偏倚采用Eggers检验和Beggs检验。结果 共17篇文献符合纳入标准,累计病例数3301例,对照组4156例。XRCC1 Arg399Gln基因多态性与中国人群HCC易感性有明显关联性（G/G vs. A/A：OR=1.32,95％CI：1.13～1.54,P=0.000;A/G vs. A/A：OR=1.25,95％CI：1.10～1.41,P=0.000;A/G+G/G vs. A／A：OR=1.22,95％CI：1.09～1.36,P=0000;G／G vs. A／A+A／G：OR=1.20,95％CI：1.04～1.39,P=0.014）。根据健康对照组来源不同的亚组分析中,所有地区或者控制人口来源医院的研究结果均显示,XRCC1 Arg399Gln 基因多态性与HCC易感性有明显关联性,但控制人口非医院来源的研究结果显示XRCC1 Arg399Gln 基因多态性与HCC易感性无明显关联性;根据地区不同分组的亚组分析中,在广西地区,除隐性遗传模型外（G/G vs. A/A+A/G：OR=1.25,95％CI：0.95～1.65,P=0.115）,其余遗传模型结果显示XRCC1 Arg399Gln基因多态性与广西地区HCC易感性有明显相关性（G/G vs. A/A：OR=1.47,95％CI：1.10～1.95,P=0.009;A/G vs. A/A：OR=1.35,95％CI：1.17～1.56,P=0.000;A/G+G/G vs.A／A：OR=133,95％CI：1.16～1.52,P=0.000）。结论 XRCC1 Arg399Gln 基因多态性可能增加中国人群HCC的易感性,尤其在广西地区。     

An Updated Meta-analysis on the Association of X-Ray Repair Cross Complementing Group 1 Codon 399 Polymorphism with Hepatocellular Carcinoma Risk

Background: A number of studies have reported the association of X-ray repair cross-complementing group1 (XRCC1) Arg399Gln polymorphism with susceptibility to hepatocellular carcinoma (HCC). However, theresults were inconsistent and inconclusive. The aim of this study was to comprehensively explore the associationof XRCC1 Arg399Gln variant with HCC risk. Materials and Methods: Systematic searches of PubMed, Elsevier,Science Direct, CNKI and Chinese Biomedical Literature Database were performed. Pooled odds ratio (OR)with 95% confidence intervals (CI) was calculated to estimate the strength of association. Results: Overall,we observed an increased HCC risk among subjects carrying XRCC1 codon 399 Gln/Gln, Arg/Gln and Gln/Gln+Arg/Gln genotypes (OR=1.20, 95%CI: 1.05-1.38, OR=1.16, 95%CI: 1.05-1.28, and OR=1.14, 95%CI:1.04-1.24, respectively) based on 20 studies including 3374 cases and 4633 controls. In subgroup analysis, weobserved an increased risk of XRCC1 codon 399 Gln/Gln, Arg/Gln and Gln/Gln+Arg/Gln polymorphisms forHCC in hospital-based study (OR=1.25, 95%CI: 1.03-1.51, OR=1.21, 95%CI: 1.07-1.36 and OR=1.18, 95%CI:1.06-1.31, respectively) and in Asian population (OR=1.19, 95%CI: 1.03-1.38, OR=1.17, 95%CI: 1.04-1.30 andOR=1.14, 95%CI: 1.04-1.25, respectively). Limiting the analysis to the studies with controls in agreement withHardy-Weinberg equilibrium (HWE), we observed an increased HCC risk among Gln/Gln, Arg/Gln and Gln/Gln+Arg/Gln genotype carriers (OR=1.17, 95%CI: 1.05-1.29, OR=1.12, 95%CI: 1.00-1.25 and OR=1.11, 95%CI:1.02-1.21, respectively). Conclusions: This updated meta-analysis results suggest that XRCC1 Arg399Gln variantsmay contribute to HCC risk. Well-designed studies with larger sample size were required to further verify ourfindings.     

XRCC1 Arg399Gln gene polymorphism and breast cancer risk: a meta-analysis based on case-control studies

Background: The Arg399Gln polymorphism in the XRCC1 DNA repair gene is likely to be involved with the development of breast cancer (BC). However, there have been inconsistent reports of association. The objective of this study was to systematically evaluate the published papers. Methods: We performed a meta-analysis of 44 published case-control studies fitting our eligibility criteria. These studies involved XRCC1 Arg399Gln polymorphisms in 20,841 BC cases and 22,688 controls in dominant (GlnGln+ArgGln vs. ArgArg), recessive (GlnGln vs. ArgGln+ArgArg), and co-dominant (GlnGln vs. ArgArg) inheritance models. Analyses of Asian, African and Caucasian ethnic subgroups was also conducted. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations. Results: Our overall analyses indicated Arg399Gln to be associated with a trend of increased BC risk when using recessive (OR=1.15, 95%CI: 1.05–1.27), and co-dominant models (OR=1.15, 95%CI: 1.04-1.27) to analyze the data. In ethnic subgroups, Arg399Gln significantly increased BC risk in Asians (OR=1.54, 95%CI: 1.18–2.01) when using recessive model analysis, in Africans (OR=1.30, 95%CI: 1.07–1.60) when using dominant model analysis, and in Asians (OR=1.50, 95%CI: 1.15–1.97) and Africans (OR=1.80, 95%CI: 1.08-3.02) when using the co-dominant model analysis. Conclusions: From our meta-analysis of data from 44 publications, we conclude that XRCC1 Arg399Gln allele is a risk factor for the development breast cancer, especially among Asian and African populations.     

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 thyroidcancer risk, but the results have been inconsistent. Thus we performed the present meta-analysis to clarify thisissue based on all of the evidence available to date. Relevant studies were retrieved by searching PubMed andstatistical analysis conducted using Stata software. Nine studies were included in this meta-analysis (1,620 casesand 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) forthe Arg399Gln polymorphism. No association of XRCC1 Arg194Trp, Arg280His and Arg399Gln polymorphismwith thyroid cancer risk was observed in the overall analysis. However, subgroup analysis revealed: 1) anelevated 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 thyroidcancer risk on subgroup analysis based on ethnicity in Aa vs AA analysis (OR=0.84, 95%CI= 0.72-0.98) and ina dominant genetic model (OR=0.84, 95%CI= 0.72-0.97) in Caucasian populations for the XRCC1 Arg399Glnpolymorphism; 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 thatthe XRCC1 Arg399Gln polymorphism may be associated with decreased thyroid cancer risk among Caucasiansand XRCC1 Arg194Trp may be associated with a tendency for increased thyroid cancer risk in the two largersample size trials.     

Genetic Association of XRCC1 Gene rs1799782, rs25487 and rs25489 Polymorphisms with Risk of Thyroid Cancer: a Systematic Review and Meta-Analysis

Background: A number of case-control studies have evaluated associations between the X-ray cross complementary group 1 protein (XRCC1) gene rs1799782 (Arg194Trp), rs25487 (Arg399Gln) and rs25489 (Arg280His) polymorphisms and thyroid cancer (TC) risk, but the results remain inconclusive. Materials and Methods: A systematic literature search was performed using PubMed and Google Scholar Search. According to defined criteria data were extracted and pooled odds ratios with 95% confidence intervals were calculated under five genetic models. Results: A total of 8 studies with 1,672 cases and 2,805 controls for the rs1799782 polymorphism, 14 studies with 2,506 cases and 5,180 controls for the rs25487 polymorphism, and 11 studies with 2,197 cases and 4,761 controls for the rs25489 polymorphism were included in this meta-analysis. Overall, there was a statistical association between XRCC1 rs1799782 polymorphism and TC risk with the homozygote genetic model (TT vs. CC: OR = 1.815, 95% CI = 1.115-2.953, p= 0.016) and the recessive genetic model (TT vs. TC+CC: OR = 1.854, 95% CI = 1.433-2.399, p= <0.001). In the subgroup analysis by ethnicity, significantly increased TC risk was observed only in Asians under the recessive model (TT vs. TC+CC: OR = 1.816, 95% CI = 1.398-2.358, p= <0.001). In addition, there was no positive association between XRCC1 rs25487 and rs25489 polymorphisms and risk of TC. However, there was a significant association between XRCC1 rs25487 polymorphism risk of TC among Caucasians with allele genetic comparison (A vs. G: OR= 0.882, 95% CI = 0.794-0.979, p= 0.136) and dominant genetic comparison (AA+AG vs. GG: OR=0.838, 95% CI = 0.728-0.965, p= 0.014). Conclusions: The results of our meta-analysis suggest an increased risk of TC with the XRCC1 rs1799782 and rs25487 polymorphisms. However, the XRCC1 rs25489 polymorphism appeared to be without influence.     

The XRCC1 Arg399Gln Genetic Polymorphism Contributes to Hepatocellular Carcinoma Susceptibility: An Updated Metaanalysis

The potential correlation of X-ray repair cross-complementing group 1 (XRCC1) Arg399Gln polymorphismwith hepatocellular carcinoma (HCC) susceptibility is ambiguous. Taking account of inconsistent results ofprevious meta-analyses and new emerging literatures, we conducted a meta-analysis covering 15 case-controldatasets to evaluate the relationship. Relevant studies from Medline, Embase and CNKI were retrieved. A fixedeffectmodel or a random-effect model, depending on between-study heterogeneity, were applied to estimatethe association between XRCC1 polymorphism Arg399Gln and HCC risk with the results presented as oddsratios (ORs) and 95% confidence intervals (95% CIs). In accordance with Hardy-Weinberg equilibrium, 15studies with data for 6,556 individuals were enrolled in this systematic review. For overall HCC,thr XRCC1polymorphism Arg399Gln was significantly associated with HCC susceptibility in a homozygote model as wellas in a dominant model (G/G vs. A/A, OR=1.253, p=0.028; G/G+A/G vs. A/A, OR= 1.281, p=0.047, respectively),but not in a heterozygote model (A/G vs. A/A, OR=1.271, p=0.066) or a recessive model (G/G vs. A/G + A/A,OR= 1.049, p=0.542). Similar results were also observed on stratification analysis by ethnicity (A/G vs. A/A,OR=1.357, p=0.025; G/G vs. A/A, OR=1.310, p=0.011; G/G+A/G vs. A/A, OR= 1.371, p=0.013). However, nopotential contribution of XRCC1 Arg399Gln polymorphism to HCC susceptibility in HBV/HCV subgroups wasidentified. No publication bias was found in this study. In conclusion, the XRCC1 Arg399Gln polymorphismcontributes to HCC susceptibility. Due to the lack of studies in Western countries, further large-sample andrigorous studies are needed to validate the findings.     

Evaluation of DNA repair gene XRCC1 polymorphism in prediction and prognosis of hepatocellular carcinoma risk

We conducted a case-control study in China to clarify the association between XRCC1-Arg399Gln polymorphism and HCC risk. A total of 150 cases and 158 controls were selected from the the Affiliated Hospital of Qingdao University from May 2008 to May 2010. XRCC1-Arg399Gln polymorphism was based upon duplex polymerase-chain-reaction with the confronting-two-pair primer (PCR-CTPP) method. All analyses were performed using the STATA statistical package. A significantly increased risk was associated with the Arg/Gln genotype (adjusted OR 1.78, 95%CI=1.13-2.79) compared with genotype Arg/Arg. In contrast, the Gln/Gln genotype had non-significant increased risk of HCC with adjusted OR (95%CI) of 1.69 (0.93-2.66). A significant association was found between positive HBsAg and Arg/Gln, with an OR of 3.43 (95% CI=1.45-8.13). Patients carrying Gln/Gln genotypes showed significantly lower median survival than Arg/Arg genotypes (HR=1.38, 95% CI=1.04-1.84). Further Kaplan-Meier analysis showed decreased median survival in Arg/Gln+Gln/Gln genotype carriers in comparison to Arg/Arg carriers (HR=1.33, 95% CI=1.02-1.76). In conclusion, we observed that XRCC1-Arg399Cln polymorphism is associated with susceptibility to HCC, and XRCC1 Gln allele genotype showed significant prognostic associations.     

Assessment of the association between XRCC1 Arg399Gln polymorphism and lung cancer in Chinese

X-ray repair cross-complementing group 1 (XRCC1) is one of the major DNA repair proteins involved in the base excision repair and plays an important role in the maintenance of genomic integrity. Polymorphisms in XRCC1 may alter the function and repair capacity of XRCC1 protein which further results in the genetic instability and lung carcinogenesis. Previous studies investigating the relationship between XRCC1 Arg399Gln polymorphism and lung cancer risk in Chinese yielded contradictory results. A meta-analysis was performed to clarify the effect of XRCC1 Arg399Gln polymorphism on lung cancer. The association was assessed by calculating the pooled odds ratio (OR) with 95 % confidence intervals (95 %CI). Nineteen studies with a total of 12,835 participants were included into this meta-analysis. Overall, there was an obvious association between XRCC1 Arg399Gln polymorphism and increased risk of lung cancer under three genetic models (Gln vs. Arg: OR?=?1.13, 95 %CI 1.01–1.25, P?=?0.029; GlnGln vs. ArArg: OR?=?1.41, 95 %CI 1.07–1.84, P?=?0.013; GlnGln vs. ArArg/ArgGln: OR?=?1.37, 95 %CI 1.07–1.76, P?=?0.013). Meta-analysis of 18 studies with high quality also found that there was an obvious association between XRCC1 Arg399Gln polymorphism and increased risk of lung cancer under three genetic models. There was no obvious risk of bias in the meta-analysis. Data from the current meta-analysis support the obvious association between XRCC1 Arg399Gln polymorphism and increased risk of lung cancer in Chinese.     

Association between the HSPA1B ±1267A/G Polymorphism and Cancer Risk: a Meta-analysis of 14 Case-Control Studies

Background: Previous epidemiological studies have suggested a potential role of the HSPA1B±1267A/G polymorphism in risk of developing cancer. However, the results were inconsistent. Therefore, we performed this meta-analysis to summarize the possible association with cancer risk. Materials and Methods: We retrieved relevant articles from PubMed, EMBASE, ISI Web of Science, Chinese Biomedical Literature and Chinese National Knowledge Infrastructure. Studies were selected using specific criteria. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess those associations. All analyses were performed using STATA software. Results: Fourteen case-control studies, including 1, 834 cancer cases and 2, 028 controls were included in this meta-analysis. Overall, the results indicated that the G allele of HSPA1B gene ±1267A/G was significantly associated with an increased cancer risk in all genetic models (G vs A: OR=1.51, 95%CI 1.17-1.95, p=0.001; GG vs AA: OR=2.93, 95%CI 1.50-5.74, p=0.002; AG vs AA: OR=1.48, 95%CI 1.10-1.98, p=0.009; GG/AG vs AA: OR=1.69, 95%CI 1.22-2.33, p=0.001; GG vs AG/AA: OR=2.31, 95%CI 1.24-4.32, p=0.009). In the subgroup analysis stratified by ethnicity, a significant association was identified in Caucasians (G vs A: OR=1.35, 95%CI 1.08-1.69, p=0.008; GG/AG vs AA: OR=1.36, 95%CI 1.09-1.70, p=0.007), but not in Asians. In the stratified analysis by cancer types, individuals with the G allele showed an increased risk of hepatocellular carcinoma compared with carriers of the A allele (OR=2.40, 95%CI 1.47-3.91, p< 0.001). Inversely, individuals with the GG genotype showed a decreased risk of gastric cancer compared with carriers of the AG/GG genotypes (GG vs AG/AA: OR=0.39, 95%CI 0.20-0.70, p=0.007). Conclusions: This meta-analysis suggests associations between the HSPA1B ±1267A/G polymorphism and risk of cancer. However, this association might be Caucasian-specific and the G allele of this polymorphism probably increases risk of hepatocellular carcinoma while decreasing risk of gastric cancer. Further well-designed studies based on larger sample sizes are needed to validate these findings.     

Association Between XRCC1 Gene Polymorphisms and Risk of Glioma Development: A Meta-analysis

Objective: Previous studies of the association between X-ray cross-complementing group 1 (XRCC1) genepolymorphisms and the gliomas risk have yielded conflicting results, and thus a meta-analysis was performedto provide a more accurate estimation. Methods: A computerized literature search of 5 electronic databases wasconducted to identify the relevant studies. Fixed or random effect models were selected based on the heterogeneitytest. Publication bias was estimated using Begg’s funnel plots and Egger’s regression test. Results: A total of 11studies (3,810 cases and 6,079 controls), 7 studies (2,928 cases and 5,048 controls), and 4 studies (1,461 cases and2,593 controls) were finally included in the analyses of the association between XRCC1 Arg399Gln, Arg194Trp,and Arg280His polymorphisms and glioma risk, respectively. The pooled results showed that GlnGln carriagewas associated with moderately increased risk of gliomas in Asians (GlnGln vs. ArgArg, OR=1.490, 95%CI1.031-2.153; GlnGln/ArgGln vs. ArgArg, OR=1.321, 95%CI 1.037- 1.684), whereas a marginal association wasrevealed in Caucasians. For the Arg194Trp polymorphism, although a significant association was shown inthe homozygous genotype comparisons (TrpTrp vs. ArgArg, OR = 2.209, 95%CI 1.398- 2.945), no significantlink was found on subgroup analysis stratified by ethnicity. With regard to the Arg280His polymorphism, nosignificant association was found in each comparison. No particular study was found to significantly influencethe pooled results, and no potential publication bias was detected. Conclusions: This meta-analysis suggestedthat the XRCC1 Arg399Gln polymorphism is moderately associated with increased risk of gliomas in Asians,while Arg194Trp and Arg280His polymorphisms demonstrated no significant influence. Due to the limited studiesand the potential confounders, further studies are needed to confirm these results.     

Polymorphism of XRCC1 and the frequency of mutation in codon 249 of the p53 gene in hepatocellular carcinoma among Guangxi population, China

In hepatocellular carcinoma (HCC), hotspot mutation in codon 249 of the p53 gene has been associated with exposure to aflatoxin B1 (AFB1). While the polymorphism of DNA repair gene X-ray repair cross-complementary group 1 (XRCC1) Arg399Gln may be related with AFB1-DNA adducts and gene mutations. Five hundred one HCCs were included in this study to investigate the role of the XRCC1 codon 399 polymorphism on hotspot mutation in codon 249 of the p53 gene. The genotypes of XRCC1 codon 399 and p53 codon 249 were examined by PCR-RFLP. The HCC patients with XRCC1 genotypes with 399 Gln (namely: XRCC1-AG/GG) exhibited a significantly higher frequency of the p53 hotspot mutations in codon 249 than those with the wild-type homozygote of XRCC1 [namely: XRCC1-AA, adjusted odds ratio (OR) = 6.77, 95% confidence interval (CI) = 4.34-10.57]. Compared with those individuals who did express XRCC1-AA as reference (OR = 1), moreover, individuals featuring XRCC1-AG/GG and AFB1-DNA adducts did experience a significantly greater frequency of the hotspot mutation in codon 249 of the p53 gene (adjusted OR = 28.37, 95% CI = 13.19-61.02, P < 0.01). This study suggests that the XRCC1 Arg399Gln polymorphism and AFB1-DNA adducts are associated with the increased frequency of the p53 mutations in codon 249.     

X-ray repair cross-complementing group 1 Arg399Gln gene polymorphism and susceptibility to colorectal cancer:a meta-analysis

X-ray repair cross-complementing group 1 (XRCC1), a DNA repair enzyme, plays a crucial role in the base excision repair by generating a single nucleotide repair patch. It has been demonstrated that the XRCC1 Arg399Gln gene polymorphism was associated with variations in XRCC1 enzyme activity. The aim of this study was to quantitatively summarize the association between the XRCC1 Arg399Gln polymorphism and susceptibility to colorectal cancer (CRC). A comprehensive search of the PubMed, Embase, and China National Knowledge Infrastructure databases was conducted for studies on the association between the XRCC1 Arg399Gln polymorphism and CRC risk. Summary odds ratio (OR) with its corresponding 95 % confidence interval (95 %CI) was estimated, in a fixed-effects model or a random-effects model when appropriate, to assess the association. Totally, 26 case–control studies with 6,979 cases and 11,470 controls were included into this meta-analysis. The pooled results of total studies showed that the XRCC1 Arg399Gln polymorphism was significantly associated with increased risk of CRC in all genetic contrast models (OR_{A vs. G}?=?1.13, 95 %CI 1.03–1.23, P _OR?=?0.008; OR_{Gln/Gln vs. Arg/Arg}?=?1.24, 95 %CI 1.04–1.46, P _OR?=?0.015; OR_{Gln/Gln vs. Arg/Gln + Arg/Arg}?=?1.19, 95 %CI 1.03–1.38, P _OR?=?0.021; OR_{Gln/Gln + Arg/Gln vs. Arg/Arg}?=?1.14, 95 %CI 1.02–1.28, P _OR?=?0.022), except for the additive contrast model (OR_{Arg/Gln vs. Arg/Arg}?=?1.11, 95 %CI 0.99–1.25, P _OR?=?0.064). The statistically significant association between the XRCC1 Arg399Gln polymorphism and CRC risk was observed among studies with high quality and in Asians, but not in Caucasians. Sensitivity analyses by sequential omission of any individual studies further identified the significant association. Publication bias was inexistent in this meta-analysis. The meta-analysis suggests that the XRCC1 Arg399Gln polymorphism is associated with increased risk of CRC.     

XRCC1 Arg399Gln Gene Polymorphism and Hepatocellular Carcinoma Risk in the Chinese Han Population: A Meta-analysis

Purpose: Numerous studies have evaluated the association between XRCC1 Arg399Gln gene polymorphismand hepatocellular carcinoma risk in the Chinese Han population. However, the results have been inconsistent.We therefore here examined whether the XRCC1 Arg399Gln gene polymorphism confers hepatocellularcarcinoma risk by conducting a meta-analysis. Methods: PubMed, Google scholar and China National KnowledgeInfrastructure databases were searched for eligible articles in English and Chinese that were published beforeApril 2012. Results: 6 studies involving 1,246 patients with hepatocellular carcinoma and 1,953 controls wereincluded. The association between XRCC1 Arg399Gln gene polymorphism and hepatocellular carcinoma inthe Chinese Han population was significant under GG vs AA (OR = 1.48, 95% CI = 1.13 to 1.94). Limiting theanalysis to the studies with controls in the Hardy-Weinberg equilibrium, the results were persistent and robust.Conclusions: In the Chinese Han population, the XRCC1 Arg399Gln gene polymorphism is associated with anincreased hepatocellular carcinoma risk.     

Updated Assessment of the Association of the XRCC1 Arg399Gln Polymorphism with Lung Cancer Risk in the Chinese Population

Background: Published studies have reported relationships between X-ray repair cross-complementing group1 (XRCC1) Arg399Gln polymorphism and lung cancer risk in Chinese population. However, the epidemiologicalresults remained controversial. The objective of this study was to clarify the association of XRCC1 Arg399Glnpolymorphism with lung cancer risk in the Chinese population. Materials and Methods: Systematic searches wereperformed through the database of Medline/Pubmed, Web of Science, Embase, CNKI and WanFang MedicalOnline. Odds ratios (ORs) with 95% confidence interval (95%CI) were calculated to estimate the strength ofthe association. Results: Overall, we observed an increased lung cancer risk among subjects carrying XRCC1codon 399 Gln/Gln genotype (OR=1.36, 95%CI: 1.09-1.71) in the Chinese population on the basis of 19 studieswith 5,416 cases and 5,782 controls. We did not observe any association between XRCC1 codon 399 Arg/Gln andArg/Gln+Gln/Gln polymorphisms and lung cancer risk (OR=1.00, 95%CI: 0.92-1.08 and OR=1.05, 95%CI: 0.97-1.13, respectively). Limiting the analysis to studies with controls in agreement with Hardy-Weinberg equilibrium(HWE), we observed an increased lung cancer risk among subjects carrying XRCC1 codon 399 Gln/Gln genotype(OR=1.18, 95%CI: 1.01-1.38). When stratified by source of control, we observed an increased lung cancer riskamong subjects carrying XRCC1 codon 399 Arg/Gln+Gln/Gln genotype on the basis of hospitalized patient-basedcontrols (OR=1.21, 95%CI: 1.04-1.42) and among subjects carrying XRCC1 codon 399 Gln/Gln genotype onthe basis of healthy subject-based controls (OR=1.22, 95%CI: 1.04-1.43). Conclusions: Our findings indicatedthat certain XRCC1 Arg399Gln variants might affect the susceptibility of lung cancer in Chinese population.Larger sample size studies are required to confirm our findings.     

Polymorphism of DNA repair gene XRCC1 and hepatocellular carcinoma risk in Chinese population

Aim: We conducted a case-control study in China to clarify the association between the XRCC1-Arg399Gln polymorphism and HCC risk. Methods: A total of 202 cases and 236 controls were selected from the the Affiliated Hospital of Qingdao University from May 2008 to May 2010. Assessment of the XRCC1-Arg399Gln polymorphism was based upon duplex polymerase-chain-reactions with the confronting-two-pair primer (PCR-CTPP) method. All analyses were performed using the STATA statistical package. Results: A significant increase in risk was associated with the Arg/Gln genotype (adjusted OR 1.55, 95%CI=1.03-2.57) compared with Arg/Arg. However, the Gln/Gln genotype had non-significant increased risk of HCC with adjusted OR (95%CI) of 1.34(0.67-2.38). There was also a significant increasewith the Arg/Gln genotype among HCC patients above 50 years old (OR=1.95, 95% CI=1.14-3.57). Additionally, the risk of HCC was moderately increased in drinkers with Arg/Gln genotype compared with never drinkers, and the adjusted OR (95% CI) was 1.89 (1.13-3.45). Conclusion: This study demonstrated that a polymorphism in a DNA repair gene may influence the risk of HCC. The XRCC1 codon Arg/Gln was thuis associated with an increased risk of HCC, especiallyin patients above 50 years old and/or with a drinking habit.     

Association Between the Pre-mir-218 Polymorphism and Cancer Risk in the Chinese Population: a Meta-Analysis

Background: Several recent studies have explored associations between pre-mir-218 polymorphism(rs11134527) and cancer risk. However, published data are still inconclusive. To obtain a more precise estimationof the relationship in the Chinese population, we carried out a meta-analysis for the first time. Materials andMethods: Through retrieval from the PubMed, Medline, Embase, Web of Science databases, China NationalKnowledge Infrastructure and the Chinese BioMedical Literature Database, a total of four studies wereanalyzed with 3,561 cases and 3,628 controls for SNP pre-mir-218 rs11134527. We calculated odds ratios (ORs)and 95% confidence intervals (95%CIs) to explore the strength of associations. Results: The results showedthat the rs11134527 polymorphism was associated with decreased cancer risk in GG versus AA and GG versusAA+AG models tested ( GG vs AA: OR=0.82, 95%CI: 0.71-0.94; GG vs AA+AG: OR=0.84, 95%CI: 0.74-0.96),and significantly decreased cervical cancer risk was observed in GG versus AA and GG versus AA+AG models(GG vs AA: OR=0.79, 95%CI: 0.66-0.94; GG vs AA+AG: OR=0.80, 95%CI: 0.68-0.94). However, no significantassociation between the rs11134527polymorphism and hepatocellular carcinoma risk was observed in allcomparison models tested (AG vs AA: OR=0.94, 95%CI: 0.79-1.11; GG vs AA: OR=0.88, 95%CI: 0.70-1.10;GG+AG vs AA: OR=0.92, 95%CI: 0.79-1.08; GG vs AA+AG: OR=0.91, 95%CI: 0.75-1.11). Conclusion: Thefindings suggest that pre-miR-218 rs11134527 polymorphism may have some relation to cancer development inChinese. However, well-designed studies with larger sample size and more detailed data are needed to confirmthese conclusions.     

Association of XRCC1 Arg399Gln Polymorphism with Colorectal Cancer Risk: A HuGE Meta Analysis of 35 Studies

Background: Non-synonymous polymorphisms in XRCC1 hase been shown to reduce effectiveness of DNArepair and be associated with risk of certain cancers. In this study we aimed to clarify any association betweenXRCC1 Arg399Gln and colorectal cancer (CRC) risk by performing a meta-analysis of published case-controlstudies. Materials and Methods: PubMed and Google Scholar were searched to explore the association betweenXRCC1 and CRC. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate theassociation strength. Publication bias was assessed by Egger’s and Begg’s tests. Results: Up to January 2015, 35case control studies involving 9,114 CRC cases and 13,948 controls were included in the present meta-analysis.The results showed that the Arg399Gln polymorphism only under an allele genetic model was associated withCRC risk (A vs. G: OR 0.128, 95% CI 0.119-0.138, p<0.001). Also, this meta-analysis suggested that the XRCC1Arg399Gln polymorphism might associated with susceptibility to CRC in Asians (A vs G: OR 0.124, 95% CI0.112-0.138, p<0.001) and Caucasian (A vs G: OR 0.132, 95% CI 0.119-0.146, p<0.001) only under an allele geneticmodel. Conclusions: This meta-analysis confirms the association between XRCC1 Arg399Gln polymorphismand CRC risk and suggests that the heterogeneity is not strongly modified by ethnicity and deviation from theHardy-Weinberg equilibrium.     

XRCC1 Arg399Gln variation and leukemia susceptibility: evidence from 2,647 cases and 5,518 controls

Previous reports implicate XRCC1 Arg399Gln polymorphism as a possible risk factor for several cancers. Increasing studies have been conducted on the association of XRCC1 Arg399Gln polymorphisms with susceptibility to leukemia. However, conflicting results have been generated. The goal of the present study was to derive a more precise estimation of the relationship. Meta-analyses assessing the association of XRCC1 Arg399Gln variation with leukemia were conducted, and subgroup analyses on ethnicity and clinical types were further performed. Eligible studies were identified for the period up to February 2013. Consequently, 16 publications including 17 case–control studies with 2,647 cases and 5,518 controls were selected for analysis. The overall data indicated a significant association of XRCC1 Arg399Gln polymorphism with leukemia risk (Gln/Gln versus Arg/Arg: OR?=?1.37, 95% confidence interval (CI)?=?1.08–1.74; dominant model: OR?=?1.23, 95%CI?=?1.03–1.46; recessive model: OR?=?1.23, 95%CI?=?1.06–1.44). In the subgroup analysis by ethnicity, Gln allele may increase leukemia susceptibility among Asians (Gln/Gln versus Arg/Arg: OR?=?1.82, 95%CI?=?1.19–2.78; dominant model: OR?=?1.53, 95%CI?=?1.00–2.33; recessive model: OR?=?1.51, 95%CI?=?1.11–2.06), but not Caucasians or mixed ethnicities. In the subgroup analysis by clinical types, increased risk was observed in acute lymphocytic leukemia (ALL) subgroup (Gln/Gln versus Arg/Arg: OR?=?1.45, 95%CI?=?1.09–1.93; recessive model: OR?=?1.30, 95%CI?=?1.00–1.69), but not in acute myeloid leukemia, chronic lymphocytic leukemia, or chronic myeloid leukemia subgroups, respectively. Collectively, the results of the present study suggest that XRCC1 Arg399Gln polymorphism might be a low-penetrant risk factor for leukemia, particularly among Asians. Homozygous Gln/Gln alleles might have a correlation with increased ALL susceptibility.     

The DNA repair gene XRCC1 and genetic susceptibility of lung cancer in a northeastern Chinese population

To evaluate the effect of DNA repair gene XRCC1 polymorphisms on the risk of lung cancer in a northeastern Chinese population, we studied five cSNPs in the XRCC1 gene, three that lead to non-synonymous changes: Arg194Trp, Arg280 His and Arg399Gln and two that lead to synonymous changes: Pro206Pro and Gln632Gln. A hospital-based case-control study consisted of 247 lung cancer cases and 253 cancer-free controls matched on age, gender and ethnicity. PCR-RFLP was used for genotyping. Carriers of the minor G-allele of Pro206Pro were at significantly increased risk of lung cancer (adjusted OR=1.96, 95% CI=1.26-3.06, P=0.003). Stratified analyses revealed a significantly decreased risk of lung cancer associated with the AG/AA genotype of Arg280His (AG+AA versus GG, OR=0.38, 95% CI=0.19-0.75, P=0.005) among never smokers, although there was no interaction between Arg280His and smoking. In a haplotype analysis, a haplotype defined by Arg194Trp(C)-Pro206Pro(G)-Arg280His(G)-Arg399Gln(G)-Gln632Gln(G) was associated with increased risk of lung cancer (OR=28.60, 95% CI=2.49-331.31, P=4.45x10(-5)). No associations were observed for the other polymorphisms or haplotypes. Our results suggest that the XRCC1 Pro206Pro polymorphism or the haplotype encompassing the minor allele may contribute to genetic susceptibility for lung cancer in this northeastern Chinese population. To our knowledge, this is first report that XRCC1 Pro206Pro influences cancer risk.     

Assessment of the association between XRCC1 Arg399Gln polymorphism and glioma susceptibility

The Arg399Gln polymorphism, located in the region of the BRCT-I interaction domain of XRCC1, has been extensively explored in its function and association with glioma risk. However, these studies generated contradictory instead of conclusive results. A meta-analysis was performed to derive a more precise evaluation of the relationship between XRCC1 Arg399Gln polymorphism and glioma risk. We searched the PubMed, EMBASE, and Web of Science and extracted 12 eligible studies with 4,062 glioma cases and 5,302 glioma-free controls for this meta-analysis. The pooled odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated to assess the strength of the association. In the overall analysis, we found that the XRCC1 Arg399Gln polymorphism was statistically associated with the risk of glioma (OR_{GG vs. AG + AA}?=?0.90, 95 % CI?=?0.84–0.97, P _{heterogeneity}?=?0.020; OR_{allele G vs. allele A}?=?0.96, 95 % CI?=?0.91–1.00, P _{heterogeneity}?=?0.110). We also observed significant association between this polymorphism and glioma risk in Asian populations. The results of the meta-analysis suggest a potential decreased susceptibility to glioma in association with the XRCC1 Arg399Gln polymorphism, especially in Asians. Yet, it is necessary to conduct future prospective explorations to gain a better insight into the impact of XRCC1 Arg399Gln polymorphism on glioma risk.