Associations Between XRCC1 Arg399Gln,Arg194Trp,and Arg280His Polymorphisms and Risk of Differentiated Thyroid Carcinoma: A Meta-analysis

Background: Associations between Arg399Gln, Arg194Trp and Arg280His polymorphisms of the XRCC1 geneand risk of differentiated thyroid carcinoma (DTC) have been widely studied but the findings are contradictory.Methods: We performed a meta-analysis in the present study using STATA 11.0 software to clarify any associations.Electronic literature databases and reference lists of relevant articles revealed a total of 10, 6 and 6 publishedstudies for the Arg399Gln, Arg194Trp and Arg280His polymorphisms, respectively. Results: No significantassociations were observed between Arg399Gln and DTC risk in all genetic models within the overall andsubgroup meta-analyses, while the Trp/Trp vs Arg/Arg and recessive model of the Arg194Trp polymorphismwas associated with DTC susceptibility, and the dominant model of Arg280His polymorphism contributed toDTC susceptibility in Caucasians. Conclusions: Our meta-analysis suggests that XRCC1 Arg194Trp may be arisk factor for DTC development.     

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.     

The XRCC1 Arg280His Gene Polymorphism and HepatocellularCarcinoma Risk: A Meta-analysis

Many studies have suggested that the XRCC1 Arg280His gene polymorphism might be involved in thedevelopment of hepatocellular carcinoma (HCC). However, the results have been inconsistent. In this study, theauthors performed a meta-analysis to assess the association between XRCC1 Arg280His and HCC susceptibility.Published literature from PubMed, EMBASE and CNKI Data was searched. Pooled odds ratios (ORs) and 95%confidence intervals (CIs) were calculated using fixed- or random- effects models when appropriate. Begg’stest was used to measure publication bias. A total of 7 case-control studies covering 1,448 HCC cases and 1,544controls were included. No significant variation in HCC risk was detected in any of the genetic models overall.In the stratified analysis, four studies with sample sizes over 300 produced similar results. The correspondingpooled ORs were not substantially altered after the exclusion of three studies deviating from Hardy-Weinbergequilibrium in the control group, which indicated reliability for our meta-analysis results.     

A Meta-Analysis for Association of XRCC1, XRCC2 and XRCC3 Polymorphisms with Susceptibility to Thyroid Cancer

Background: We conducted a comprehensive meta-analysis to explore the association of polymorphisms at XRCC1, XRCC2 and XRCC3 genes with susceptibility to thyroid cancer (TC). Methods: We searched PubMed, EMBASE, Web of Science, and CNKI for relevant available studies. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the strength of the associations. Results: A total of 67 studies including 17 studies with 6,806 cases and 5,229 controls on XRCC1 Arg399Gln, 13 studies with 3,234 cases and 4,807 controls on XRCC1 Arg280His, 13 studies with 2,956 cases and 3,860 controls on XRCC1 Arg194Trp, five studies with 1,287 cases and 1,422 controls on XRCC2 Arg188His, 13 studies with 2,488 cases and 3,586 controls on XRCC3 Thr241Met, and six studies with 1,828 cases and 2,060 controls on XRCC3 IVS5-14 polymorphism were selected. Polled data revealed that the XRCC1 Arg399Gln, Arg280His, Arg194Trp, XRCC2 Arg188His and XRCC3 Thr241Met and IVS5-14 polymorphisms were not significantly associated with an increased risk of TC. Stratified analyses by ethnicity showed that the XRCC1 Arg399Gln polymorphism was associated with TC risk in Caucasians, but not in Asians. Conclusions: Our meta-analysis indicated that the XRCC1 Arg399Gln, Arg280His, Arg194Trp, XRCC2 Arg188His, XRCC3 Thr241Met and IVS5-14 polymorphisms were not associated with risk of TC in the global population.  Further well-designed investigations with large sample sizes are required to confirm our results.     

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.     

Polymorphisms of XRCC1 and ADPRT Genes and Risk of Noncardia Gastric Cancer in a Chinese Population: a Casecontrol Study

Objective: Gastric cancer (GC) is one of the most common malignancies and its mortality ranks third amongall cancers in China. We previously noted that XRCC1 Arg194Trp was associated with GC risk in WesternChina in a study on XRCC1 Arg194Trp and ADPRT Val762Ala. We aimed to further explore the associationof these polymorphisms with risk of the noncardia subtype. Methods: We enrolled 176 noncardia GC patientsand 308 controls from four hospitals and a community between October 2010 and August 2011. Genotyping wasperformed in a 384-well plate format on the Sequenom MassARRAY platform. A self-designed questionnairewas utilized to collect epidemiological data from the subjects regarding demographic factors and potential riskfactors. Results: Subjects were aged 56.8±11.8 (mean ± standard deviation) and 57.6±11.1 years in the caseand control groups, respectively. Individuals carrying the XRCC1 Trp/Trp or Arg/Trp variant genotype wereat significantly increased risk of noncardia GC (adjusted OR, 1.48; 95% CI, 1.00-2.17), after adjustment forfamily history of cancer, drinking, and smoking. The increased risk of XRCC1 Arg194Trp variant genotypewas more pronounced among subjects below 60 years old (adjusted OR, 1.78; 95% CI, 1.07-2.96), comparedto older individuals. ADPRT Val762Ala variants (Ala/Ala or Val/Ala) were not associated with noncardia GC(adjusted OR, 1.03; 95% CI, 0.69-1.54). Conclusions: Our study suggests that XRCC1 Arg194Trp is a geneticsusceptibility factor for developing noncardia GC in Han Chinese in Western China. In particular, individualswith the XRCC1 Arg194Trp variant genotype are at increased risk for GC below 60 years old.     

Association between the XRCC1 Arg194Trp Polymorphism and Glioma Risk: an Updated Meta-analysis

Gliomas are the most common type of primary brain tumors. The XRCC1 Arg194Trp variant affects the proliferating cell nuclear antigen( PCNA) binding region, which suggests that this mutation may contribute to gliomagenesis and a number of articles have examine the association between XRCC1 Arg194Trp and the susceptibility to glioma. However, the results were conflicting. Test of heterogeneity, sensitivity analysis, metaanalysis, and assessment of publication bias were all performed in our present meta-analysis, covering a total of5,407 patients and 7,715 healthy persons. In the overall analysis the XRCC1 Arg194Trp polymorphism showed a significant association with glioma susceptibility in a recessive mode l(for TrpTrp vs ArgArg+ArgTrp: OR=1.918,95%CI=1.575-2.336, I2=2.3%). In addition, analysis of subgroups presented an increased risk in Asians and populations-based on hospitals. The results suggested that the XRCC1 Arg194Trp polymorphism is a genetic risk factor for glioma, especially in Asian population. To further evaluate gene-gene and gene-environment interactions on XRCC1 polymorphisms and glioma risk, thousands of subjects and tissue-specific biochemical characterizations are required.     

Association Between Polymorphisms of XRCC1 Arg399Gln and XPD Lys751Gln Genes and Prognosis of Colorectal Cancer in a Chinese Population

We conducted this study to detect associations between XRCC1 Arg399Gln and XPD Lys751Gln genotypesand survival of colorectal cancer patients treated with 5-FU/oxalipatin chemotherapy. We included 289 Chinesepatients with advanced colorectal cancer, who had received 5-FU/oxalipatin chemotherapy as first-line treatmentfrom January 2005 to January 2007. All patients were followed up till Nov. 2011. Genotyping for XRCC1Arg399Gln and XPD Lys751Gln polymorphisms was based upon duplex polymerase-chain-reaction with thePCR-RFLP method. In our study, we found the XRCC1 399 Gln/Gln genotype to confer significantly higherrates of response to chemotherapy when compared to the Arg/Arg genotype [OR (95% CI)= 2.56(1.57-2.55)].patients with the XPD 751 Gln/Gln genotype had significantly higher rates of response to chemotherapy [OR(95% CI)= 1.54(0.87-2.65)] and those with the XRCC1 399 Gln/Gln genotype had a longer average survivaltime and significantly lower risk of death than did those with the Arg/Arg genotype [HR (95% CI)= 0.66(0.36-0.95)]. Similarly, those carrying the XPD 751Gln/Gln genotype had 0.51-fold the risk of death of those with XPD751Lys/Lys [HR (95% CI)= 0.51(0.33 -0.94)]. In conclusion, it is suggested that the XRCC1 Arg399Gln and XPDLys751Gln polymorphisms should be routinely assessed to determine colorectal patients who are more likely tobenefit from 5-FU/oxalipatin chemotherapy.     

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.     

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.     

Association of XPD and XRCC1 Genetic Polymorphisms with Hepatocellular Carcinoma Risk

Aim: XRCC1 and XPD are two major repair genes involved in nucleotide excision repair (NER), whichis reported to be associated with risk of several cancers. We explored the association of XRCC1 and XPDpolymorphisms with the risk of HCC. Methods: A total of 410 cases with HCC and 410 health controls werecollected. XRCC1 Arg194Trp, XRCC1 Arg399Gln, XPD Lys751Gln and XPD Asp312Asn genotyping wasperformed by duplex polymerase-chain-reaction with the confronting-two-pair primer (PCR-CTPP) method.Results: XRCC1 194Trp/Trp was strongly significantly associated with an increased risk of HCC cancer whencompared with the wide-type genotype (OR=2.26, 95% CI=(1.23-5.38). Individuals carrying the XRCC1 399Gln/Gln showed increased risk of HCC (OR=1.74, 95%CI=1.06-2.74). The XPD 751Gln/Gln and Gln allele genotypewere associated with strong elevated susceptibility to HCC (OR=3.51 and 1.42, respectively). Conclusion: Theseresults suggest that polymorphisms in XRCC1 and XPD may have functional significance in risk of HCC.     

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.     

Polymorphisms of XRCC1 and XRCC2 DNA Repair Genes and Interaction with Environmental Factors Influence the Risk of Nasopharyngeal Carcinoma in Northeast India

Multiple genetic and environmental factors have been reported to play key role in the development of nasopharyngeal carcinoma (NPC). Here, we investigated interactions of XRCC1 Arg399Gln and XRCC2 Arg188His polymorphisms and environmental factors in modulating susceptibility to NPC in Northeast India. One-hundred NPC patients, 90 first-degree relatives of patients and 120 controls were enrolled in the study. XRCC1 Arg399Gln and XRCC2 Arg188His polymorphisms were determined using PCR-RFLP, and the results were confirmed by DNA sequencing. Logistic regression (LR) and multifactor dimensionality reduction (MDR) approaches were applied for statistical analysis. The XRCC1 Gln/Gln genotype showed increased risk (OR=2.76; P<0.024) of NPC. However, individuals with both XRCC1 and XRCC2 polymorphic variants had 3.2 fold elevated risk (P<0.041). An enhanced risk of NPC was also observed in smoked meat (OR=4.07; P=0.004) and fermented fish consumers (OR=4.34, P=0.001), and tobacco-betel quid chewers (OR=7.00; P=0.0001) carrying XRCC1 polymorphic variants. However, smokers carrying defective XRCC1 gene showed the highest risk (OR = 7.47; P<0.0001). On MDR analysis, the best model for NPC risk was the five-factor model combination of XRCC1 variant genotype, fermented fish, smoked meat, smoking and chewing (CVC=10/10; TBA=0.636; P<0.0001); whereas in interaction entropy graphs, smoked meat and tobacco chewing showed synergistic interactions with XRCC1. These findings suggest that interaction of genetic and environmental factors might increase susceptibility to NPC in Northeast Indian populations.     

DNA修复基因XRCC1在宫颈癌中的表达

目的　探讨DNA修复基因XRCC1在宫颈癌组织中的表达及其临床意义。方法　应用免疫组织化学SP法 ,检测 10例正常宫颈 ,60例宫颈鳞癌和 9例宫颈腺癌组织中XRCC1的表达水平。结果　在宫颈癌组织中XRCC1的阳性表达率为 66 7% (4 6/67) ;与正常宫颈组织中比较 ,有显著差异 (P <0 0 5 ) ;XRCC1在宫颈癌中的表达与临床分期及组织学分级有关 (P <0 0 1) ,与淋巴结转移和病理类型无关 (P >0 0 5 )。结论　DNA修复基因XRCC1与宫颈癌的发生发展密切相关。     

中国人群中XRCC1 Arg194Trp位点多态性和结直肠癌易感性关系的Meta分析

目的: 探讨中国人群中X射线交叉互补修复基因1(XRCC1)的194位点(Arg194Trp)多态性与结直肠癌(CRC)易感性的关系。方法: 检索万方数据知识服务平台、中国生物医学数据库(CBM)、中国知网(CNKI)、维普数据库(VIP)、PubMed、EBASE等数据库,获取有关XRCC1 Arg194Trp位点多态性与结直肠癌易感性关系的文献,应用Meta分析软件Review Manager 5.1对最终纳入的文献进行综合定量评价,并进行异质性分析、敏感性分析、发表偏倚分析及亚组分析。结果: 经过筛选最终纳入10个研究。Meta分析结果示纯合子模型的合并OR=1.40,95%CI(1.13~1.73),P=0.002;显性模型的合并OR=1.22,95%CI(1.01~1.47),P=0.04;隐性模型的合并OR=1.30,95%CI(1.06~1.60),P=0.01;杂合子模型的合并OR=1.19,95%CI(1.00~1.42),P=0.05。在亚组分析中,病例组吸烟者和对照组吸烟者的OR=1.04,95%CI(0.84~1.29),P=0.72;病例组饮酒者和对照组饮酒者的OR=1.08,95%CI(0.81~1.44),P=0.60。结论: XRCC1 Arg194Trp位点多态性和结直肠癌易感性有关系,在纯合子模型、显性模型及隐性模型中携带194Trp基因型个体发生结直肠癌的危险性会增加,吸烟、饮酒与结直肠癌发病率无明显关联。     

Polymorphisms of the XRCC1 and XPD Genes and Breast Cancer Risk: A Case-Control Study

The purpose of this case control study was to evaluate the role of X-ray repair cross-complementing group 1 (XRCC1) and xeroderma pigmentosum group D (XPD) genotypes as genetic indicators of susceptibility to breast cancer (BC). We analysed DNA samples from 114 breast cancer patients and 113 control subjects using polymerase chain reaction-restriction fragment length polymorphism. For the single nucleotide polymorphisms in XRCC1 exon 10 (Arg399Gln, G/A) and XPD exon 23 (Lys751Gln, A/C), no remarkable differences for genotype distribution and allele frequencies were observed between BC group and control group in the study. The genotype frequency for homozygote A/A in XPD exon 6 (Arg156Arg, C/A) were significantly different between BC and control groups (P < 0.0001, odds ratio = 2.14; 95% confidence interval 1.44-3.17). The data indicate a possible role for XPD (Arg156Arg, C/A) polymorphisms in BC susceptibility.     

中国人DNA修复基因XRCC1 Pro206Pro和Gln632Gln单核苷酸多态与肺癌发生风险

目的:DNA修复系统基因在维持基因组整体性及预防癌变过程中起着重要作用。碱基切除修复是DNA修复途径之一,主要切除DNA分子的小型损伤。XRCC1蛋白分子是碱基切除修复途径的重要组成成分。本研究探讨了DNA修复基因XRCC1 Pro206Pro与Gln632Gln单核苷酸多态与肺癌发生风险。方法:采用PCR-RFLP分型技术,分析中国东北地区汉族群体中247例肺癌患者与253例正常对照者的XRCC1 Pro206Pro和Gln632Gln多态/单体型与肺癌易感性及其与吸烟之间的关联。肺癌病例与正常对照者在年龄(±3岁)、性别及民族方面相配对。结果:XRCC1 Pro206Pro(G)变异等位基因携带者与AA野生等位基因纯合子个体相比较,有1.96倍高的肺癌发生风险(ad-justedOR=1.96,95%CI=1.26～3.06,P=0.003)(OR值经吸烟史校正)。对于XRCC1 Gln632Gln单一位点研究,未发现有统计学意义。分层分析未观察到基因型与吸烟史之间可能的基因与环境的相互作用。两个SNPs之间存在强烈的连锁不平衡(D'=0.807,P=3.1e-115),单体型在肺癌组与对照组之间的总体分布有极显著性差异(P=2.25e-06)。单体型2(Pro206Pro(A)-Gln632Gln(G)是抗风险性单体型(OR=0.66,95%CI=0.45～0.96,P=0.03),而单体型4(Pro206Pro(G)-Gln632Gln(G)是高风险性单体型(OR=16.09,95%CI=3.89～66.53,P=3.09e-07),这表明了基因与基因之间的相互作用对于复杂疾病研究的重要性。结论:XRCC1Pro206Pro等位基因及含其等位基因的单体型可能在肺癌的发生过程中起着重要作用。     

DNA修复基因XRCC1基因多态性与乳腺癌临床病理参数的相关性

目的 :研究XRCC1基因Arg194Trp和Arg399Gln多态性与中国女性乳腺癌临床病理参数的关系,探讨其在乳腺癌预后中的潜在意义。 方法 :采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法,对250例原发性乳腺癌患者进行XRCC1基因Arg194Trp、Arg399Gln多态性分析,用Pearsonχ²检验分析基因型与临床病理特征的关系。 结果 :XRCC1基因Arg194Trp和Arg399Gln多态性与乳腺癌患者的月经状态、肿瘤大小、腋窝淋巴结转移、TNM分期、雌激素受体均无显著相关性(P>0.05)。但该多态位点与乳腺癌患者的孕激素受体(PR)状态和C-erbB2蛋白表达显著相关。携带194纯合突变型的患者PR阴性率(81.0%)显著高于携带194野生型和杂合型患者(55.4%),(P=0.034);携带399纯合突变型的患者C-erbB2蛋白表达阳性率(61.1%)显著高于携带399野生型和杂合型的患者(29.3%),(P=0.006)。 结论 :PR阴性和(或)C-erbB2高表达的乳腺癌患者常提示预后不良。XRCC1基因多态性与PR阴性或C-erbB2高表达显著相关,提示携带XRCC1纯合突变(194或399)乳腺癌患者可能预后不良。     

XRCC1 Polymorphisms are Associated with Cervical Cancer Risk and Response to Chemotherapy: a Systematic Review and Meta-analysis

Background: Functional single nucleotide polymorphisms of x-ray repair cross-complementing protein1 (XRCC1) have been suspected to contribute to uterine cervical cancer risk for a long time; however, mostprevious case-control studies were small sized and biased. Additionally, recent studies suggested that XRCC1polymorphisms could be a biomarker of response to platinum-based chemotherapy. Methods: A comprehensivesearch was conducted to retrieve eligible studies and odds ratios (ORs) and 95% confidence intervals (95% CIs)were calculated to measure association strength. Results: A total of 13 studies were identified and analyzed. Wefound that the Arg194Trp polymorphism (Trp vs. Arg, OR=1.342, 95% CI: 1.176) was associated with increasedrisk of cervical cancer, while no significant association was found with Arg280His (His vs. Arg, OR=1.059, 95%CI: 0.863, 1.299) or Arg399Gln (Gln vs. Arg, OR=1.144, 95% CI: 0.938, 1.394). As for response to platinumbasedchemotherapy, the variant XRCC1 399Gln allele (Gln vs. Arg, OR=0.345, 95% CI: 0.163, 0.729) waslinked with a poor response; however, the Arg194Trp polymorphism (TrpArg vs. ArgArg, OR=6.421, 95% CI:1.573, 26.205) predicted a good response. Conclusion: The Arg194Trp polymorphism of XRCC1 increases riskof cervical cancer; the variant 399Gln allele predicts poor response to platinum-based chemotherapy, while theArg194Trp polymorphism indicates a good response.     

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.