XRCC 1 Arg399Gln基因多态性对铂类药物化疗胃癌患者预后的影响

目的：研究DNA修复酶X射线损伤交叉互补蛋白1（X-ray repair cross-complementary protein1，XRCCl）基因Arg399Gln多态性对接受铂类药物辅助化疗的胃癌患者预后的影响。方法：选取经病理学确诊的胃癌患者84例，采用含铂类药物的联合化疗方案进行辅助化疗。化疗前采集患者外周血，采用聚合酶链反应．连接酶检测反应（polymerase chain reaction-ligation detection reaction，PCR-LDR）技术检测XRCCl基因Arg399Gln的多态性。结果：84例胃癌患者中，49例（58．3％）携带XRCCl的399Axg／Arg基因型，30例（35．7％）携带Arg／Gln基因型，5例（6．0％）携带Gin／Gin基因型；截止到随访结束，分别有63．1％（53／84）和55．2％（43／84）的患者出现复发和死亡，其中携带Arg／Arg基因型的胃癌患者复发率和死亡率均显著低于携带Arg／Gln或Gln／Gln基因型患者（P〈0.05）。COX多因素分析显示，携带Arg／Arg基因型的患者具有较好的无复发生存期和总生存期预后（P〈0．05）。结论：XRCClArg399Gln基因多态性与术后胃癌患者接受铂类药物化疗后的预后有关，可以在一定程度上判断术后胃癌患者接受铂类药物化疗的预后情况。     

广西扶绥县肝癌家系XRCC1基因Arg399Gln多态性与肝细胞癌的遗传易感性

目的研究广西扶绥县肝癌家系人群DNA修复基因XRCC1Arg399Gln多态性与肝细胞癌（HCC）遗传易感性的相关性。方法采用病例-对照研究方法,对扶绥县21个肝癌家系人群和10个正常家系人群,运用PCR-RFLP方法分析XRCC1基因Arg399Gln位点多态性,并应用Logistic回归模型分析该位点多态性与肝细胞癌遗传易感性的关系。结果通过XRCC1Arg399Gln基因型检测分型,肝癌家系人群携带变异等位基因Gln的频率为23.68%,正常家系人群为13.16%,等位基因在两组间的分布差异无统计学意义（P〉0.05）。基因型分布符合Hardy-Weinberg平衡定律。正常家系人群中携带Arg/Gln者发生HCC的风险是携带Arg/Arg者的1.622倍（95%CI=0.475～5.541,P=0.440）。肝癌家系人群中除肝癌患者外,携带Arg/Gln、Gln/Gln者发生HCC的风险分别是携带Arg/Arg者的1.198倍（95%CI=0.362～3.968）和2.964倍（95%CI=0.434～20.220,P分别为0.768、0.267）。结论广西扶绥县肝癌家系人群中,XRCC1399Arg/Gln基因型和Gln/Gln基因型者患HCC的风险较Arg/Arg基因型者有增加的趋势,但不存在显著相关性。     

XRCC1基因Arg399Gln多态性与中国人群神经胶质瘤易感性Meta分析

目的:探讨XRCC1基因Arg399Gln (G/A)多态性与中国人群神经胶质瘤易感性的关系.方法:计算机检索Pubmed、EMBASE、中国知网、万方期刊、维普等中英文数据库,检索2014年10月之前公开发表的相关文献,对符合标准的文献采用NOS量表评价文献质量,应用RevMan5.1软件进行Meta分析.结果:共纳入9篇与XRCC1基因Arg399Gln多态性与神经胶质瘤易感性相关的病例对照研究,包括7 131例患者,其中病例组3 428例,对照组3 703例,NOS评分≥6分为高质量文献,仅2项研究质量评分＜6.Meta分析结果显示携带A等位基因可增加中国人群神经胶质瘤的患病风险(OR=1.20,95％CI:1.04～1.38,P=0.01).结论:中国人群中XRCC1基因Arg399Gln (G/A)多态性与神经胶质瘤的易感性存在相关性.     

XRCC1 Arg399Gln位点多态性与乳腺癌易感性的Meta分析

[目的]评估X射线交叉互补修复基因1(X-ray repair cross complementing protein 1,XRCC1)基因Arg399Gln位点单核苷酸多态性与高加索及亚洲人群乳腺癌(breast cancer,BC)易感性的关系。[方法]检索Pub Med、Embase、中国期刊全文数据库(CNKI)、万方数据库、中国生物医学文献数据库(CBM)和中文科技期刊全文数据库(VIP)等数据库,获取有关XRCC1 Arg399Gln位点多态性与高加索及亚洲人群乳腺癌易感性关系的病例对照研究的资料,以病例组及对照组XRCC1 Arg 399Gln等位基因分布的比值比(OR)为效应指标,应用Meta分析软件Review Manager(version 5.0.10)对各研究原始数据进行统计处理及异质性检验,计算合并OR值及其95%可信区间。[结果 ]共纳入24项病例对照研究,包括15151例乳腺癌患者和17179例对照。Meta分析结果显示,XRCC1 Arg399Gln位点Gln/Gln突变型可能会增加亚洲人群乳腺癌的发病风险[Gln/Gln vs.Arg/Arg亚洲组:OR=1.20(95%CI:1.03~1.39),P=0.02;Gln/Gln vs.Arg/Arg+Arg/Gln亚洲组:OR=1.20(95%CI:1.04~1.38),P=0.01。Gln/Gln vs.Arg/Arg OR=1.01(95%CI:0.94~1.09),Z=0.35,POR=0.73;Gln/Gln+Arg/Gln vs.Arg/Arg OR=1.02(95%CI:0.95~1.09,Z=0.58,POR=0.56;Gln/Gln vs.Arg/Arg+Arg/Gln OR=1.01(95%CI:0.95~1.08),Z=0.33,POR=0.74)。[结论]XRCC1 Arg399Gln位点Gln/Gln突变型可能与亚洲人群乳腺癌易感性相关。     

中国人群XRCC1 Arg399Gln 基因多态性与结直肠癌易感性关系的Meta分析

摘 要：［目的］探讨X线修复交叉互补基因1（X-ray repair cross complementing group 1,XRCC1）Arg399Gln基因多态性与中国人群结直肠癌易感性的关系。［方法］在PubMed、MEDLINE、EMBASE、中国知网、维普、中国生物医学文献及万方数据库中检索建库至2016年4月10日之间发表的有关XRCC1 Arg399Gln基因多态性与中国人群结直肠癌易感性关系的相关文献。按照纳入和排除标准独立选择文献、提取资料,采用Stata 12.0软件进行Meta分析,计算合并比值比（OR）及其95%可信区间（95%CI）,并进行敏感性分析和发表偏倚的估计。［结果］ 共纳入11项研究,包括3502例患者和4828例对照者。Meta分析结果显示,在Gln/Gln vs Arg/Gln遗传模型中,XRCC1 Arg399Gln基因多态性与中国人群结直肠癌发生风险有显著相关性,与基因型Arg/Gln相比,基因型Gln/Gln增加了中国人群罹患结直肠癌的风险（OR=1.23,95%CI：1.04~1.46,P=0.016）。其余遗传模型中两者间无明显相关性。［结论］ 在Gln/Gln vs Arg/Gln遗传模型中,XRCC1 Arg399Gln基因多态性与中国人群结直肠癌易感性相关,基因型Gln/Gln增加中国人群罹患结直肠癌的风险。     

XRCC1 Arg399Gln位点多态性和结直肠癌易感性关系的Meta分析

[目的]探讨X射线交叉互补修复基因1（X-ray repair cross-complementing group1,XRCC1）的399位点（Arg399Gln）多态性与结直肠癌（CRC）易感性的关系。[方法]检索中国生物医学数据库（CBM）、PubMed、Springer等数据库,获取有关XRCC1Arg399Gln多态性同结直肠癌易感性关系的病例对照研究并进行Meta分析,以病例组及对照组XRCC1Arg399Gln等位基因分布的比值比（OR）为效应指标,应用Meta分析软件Review Manager（version5.0.10）对各研究原始数据进行统计处理及异质性检验,计算合并OR值及其95%可信区间（95%CI）。[结果]纳入11项病例对照研究,共2287例结直肠癌患者和3485例对照,Meta分析结果显示,Gln/Gln vs.Arg/Arg OR=1.12,95%CI为0.76～1.65,Z=0.58,POR=0.56;Gln/Gln＋Arg/Gln vs.Arg/Arg OR=1.11,95%CI为0.85～1.44,Z=0.78,POR=0.43;Gln/Glnvs.Arg/Arg＋Arg/Gln OR=1.07,95%CI为0.79～1.46,Z=0.43,POR=0.67;Arg/Gln vs.Arg/Arg OR=1.14,95%CI为0.88～1.48,Z=1.02,POR=0.31。[结论]XRCC1Arg399Gln多态性与结直肠癌易感性之间无显著相关性。     

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。     

中国人DNA修复基因XRCC1单核苷酸多态及其与食管癌风险的关系

目的：研究碱基切除修复基因ＸＲＣＣ１单核苷酸多态与食管癌易感性的关系。方法：以ＰＣＲ－ＲＦＬＰ方法分析了食管癌病例（ ｎ＝２２２）和按性别、年龄频数配对的正常对照者（ ｎ＝４３３） ＸＲＣＣ１基因 Ｃ２６３０４Ｔ和 Ｇ２８１５２Ａ多态,并比较不同基因型与食管癌风险的关系以及基因多态与吸烟之间的交互作用对食管癌风险的影响。结果：在食管癌病人中ＸＲＣＣ１　２６３０４ＴＴ变异基因型频率为１２．６％,高于对照组的６．７％（Ｐ＜０．０５）;携带此种基因型个体发生食管癌的风险比携带其他基因型者高１． ８倍（校正的ＯＲ＝１．８３, ９５％ ＣＩ　１．０３～３．２４）。Ｇ２８１５２Ａ基因型频率在对照组和病例组中的分布无显著性差异（Ｐ＞０．０５）,因而与食管癌风险无关。ＸＲＣＣ１基因这两个位点多态之间没有联合作用,但２６３０４ＴＴ基因型与吸烟之间有一定的协同作用,在吸烟与否和吸烟量两个层次,２６３０４ＴＴ基因型均与之有联合作用而增高食管癌风险。结论：ＤＮＡ碱基切除修复基因ＸＲＣＣ１多态可能在食管癌的发生过程中起一定作用。     

XRCC1基因多态性与放射性损伤

X线修复交叉互补基因1(XRCC1)是一种重要的DNA修复基因,该基因的多态性会导致其编码蛋白相应的氨基酸改变,影响DNA修复,进而造成肿瘤患者的放射性损伤.目前研究发现,XRCC1单核苷酸多态性与肿瘤患者放射性损伤相关,但其相关性需进一步深入研究.     

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 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.     

An updated meta-analysis between the association of XRCC1 Arg399Gln polymorphism and hepatocellular carcinoma risk

Background: Various studies have evaluated the relationship between X-ray repair cross-complementinggroup 1 (XRCC1) Arg399Gln polymorphism and hepatocellular carcinoma (HCC) risk, but the conclusionshave been inconsistent and underpowered. The purpose of this updated meta-analysis was to examine whetherXRCC1 Arg399Gln polymorphism confers susceptibility to HCC. Methods: Eligible studies extracted fromPubMed, Embase, Cochrane Library, VIP (chinese) and CNKI (chinese) up to November 2013 were included inthe study. Pooled odds ratio (OR) together with their 95% confidence interval (CI) were estimated to evaluateXRCC1 Arg399Gln polymorphism and HCC risk. Results: Finally, 21 studies with 4,170 cases and 5,030controls were involved in our meta-analysis. The results demonstrated that there was significant associationbetween Arg399Gln polymorphism and HCC risk under two contrast models in overall populations (AG vs GG:OR=1.265, 95%CI=1.036-1.545, p=0.021; AA+AG vs GG: OR=1.240, 95%CI=1.021-1.506, p=0.030). In subgroupanalyses, significant association was found in Asians (A vs G: OR=1.175, 95%CI=1.013-1.362, p=0.033; AG vsGG: OR=1.317, 95%CI=1.070-1.622, p=0.009; AA+AG vs GG: OR=1.289, 95%CI=1.055-1.575, p=0.013) andCaucasians (A vs G: OR=0.591, 95%CI=0.361-0.966, p=0.036; AA+AG vs GG: OR=0.468, 95%CI=0.234-0.934,p=0.031). Conclusions: The results suggest that XRCC1 Arg399Gln polymorphism may increase HCC riskespecially among Asians. However, XRCC1 Arg399Gln polymorphism might act as a protective role againstHCC among Caucasians.     

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.     

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.     

The Codon 399 Arg/Gln XRCC1 Polymorphism is Associated with Lung Cancer in Indians

Background: The XRCC1 (X-ray repair cross complimenting group-I) gene in BER (base excision repair)pathway is essential for DNA repair process. Polymorphisms in this gene are associated with variations in the repairefficiency which might predispose individuals to development of various cancers. Two variants of XRCC1gene(at codon 399), Gln/Gln and Arg/Gln, have been shown to be related to lowered DNA repair capacity andincreased genomic instability in multiple studies. Hence our investigation focused on genotyping these variantsto correlate with other multiple risk factors in lung cancer (NSCLC) patients since we hypothesized that thesevariants of the XRCC1 gene might influence disease susceptibility. Materials and Methods: We examined thefrequency of the polymorphism in one hundred cases and an almost equal number of controls after recordingtheir demographics with a structured questionnaire. Genomic DNA from blood samples was extracted for PCRstudies, followed by RFLP to determine the variants. The significance of the data was statistically analyzed.Results: The three genotypes in cases and controls were Arg/Arg (40% and 54.45%); Gln/Gln (19% and 9.90%),and Arg/Gln (41.0% and 35.64%) respectively. Among these 3 genotypes, we found Gln/Gln and Arg/Gln toshow association with lung cancer. Correlating these genotypes with several parameters, we also found that thesetwo variants were associated with risk in males (p<0.05) and with smoking habits (p<0.05). In females Arg/Glngenotype showed association with stage of the disease (p=0.04). This is the first report in South Indian scenariowhere Arg399Gln genotypes were found to be associated with stage of the disease in females. Conclusions: Itis concluded that XRCC1 genotypes Gln/Gln and Arg/Gln may influence cancer susceptibility in patients withsmoking habits and these functional SNPs in XRCC1 gene may act as attractive candidate biomarkers in lungcancer for diagnosis and prognosis.     

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.