修复基因XRCC1 Arg194Trp位点多态性与肝癌易感性的关系

目的：探讨DNA损伤修复基因XRCC1多态与肝癌遗传易感性的关系。方法：本研究选取了130例肝癌患者及130例性别、年龄相匹配的正常对照者进行研究,采用限制性片段长度多态性方法,比较不同基因型与肝癌发病的关系。结果：变异型等位基因XRCC1 Arg/Trp及Trp/Trp的出现率在肝癌组和对照组中分别是27.69%和10.77%,（P〈0.05）;而野生基因型XRCC1 Arg/Arg出现率在肝癌组和对照组中分别是72.31和89.23%,（P〉0.05）。结论：XRCC1基因Arg194Trp位点单核苷酸多态在肝癌的发生过程中起着至关重要的作用。     

XRCC 1194Arg/Trp基因多态与晚期乳腺癌患者铂类方案近期疗效的相关研究

目的研究XRCC1 194Arg/Trp基因多态与晚期乳腺癌铂类方案近期疗效的关系。方法 56例晚期乳腺癌患者接受含铂类方案一线治疗,分析XRCC1 194Arg/Trp基因多态与患者临床获益率及无进展生存期的相关性。结果Arg/Arg、Arg/Trp和Trp/Trp基因型临床获益组和非临床获益组分布频率分别为30.6%、55.6%、13.8%和55.0%、35.0%、10.0%。Trp/Trp＋Arg/Trp基因型患者临床获益率高于Arg/Arg型患者,分别为73.5%和50.0%,经年龄、术时分期校正后,P=0.055。Trp/Trp＋Arg/Trp及Arg/Arg基因型患者2年无进展生存率分别为43.5%和34.1%,无显著性差异（P=0.460）。结论 XRCC1 194Arg/Trp基因多态可能成为晚期乳腺癌患者铂类方案治疗效果的预测指标。     

DNA修复酶XRCC1基因多态与非小细胞肺癌对GP方案化疗的敏感性

目的 研究DNA修复酶XRCC1基因Codon 194和Codon 399多态与非小细胞肺癌（NSCLC）患者对吉西他滨/顺铂（GP）方案化疗敏感性的关系.方法 收集经病理学确诊的NSCLC 57例,所有病例化疗前抽静脉血,提取白细胞DNA,用PCR-RFLP技术检测XRCC1 194和399基因型.所有患者均经PDD/GEM化疗方案治疗.结果 ①NSCLC患者中,XRCC1 194 Arg/Arg、 Arg/Trp 、Trp/Trp基因型者分别为30例（52.6%）、23例（40.4%）和4例（7.0%）;XRCC1 399 Arg/Arg、 Arg/Gln、Gln/Gln基因型者分别为31例（54.4%）、23例（40.3%）和3例（5.3%）.经化疗后,19例患者有效,总有效率33.3%.②XRCC1 194 Trp/Trp、Tp/Arg和Arg/Arg基因型者的化疗有效率分别为50.0%、52.2%和16.7%.携带Trp等位基因者的化疗有效率（51.9%）显著高于Arg/Arg基因型者（χ^2=6.41,P=0.0113）;XRCC1 399 Arg/Arg、Arg/Gln和Gln/Gln基因型者的化疗有效率分别为35.5%、34.8%和0,各组间的差异无显著性.XRCC1 194与XRCC1 399多态之间在化疗敏感性方面存在明显的交互作用,同时携带194 Arg/Arg和399 Arg/Arg基因型者的化疗有效率仅为7.7%（1/13）,而同时携带XRCC1 194 Trp等位基因和399 Arg/Arg基因型者的化疗有效率为58.8%（10/17）,2组之间差异显著（Fisher＇s双侧检验：P=0.0067）.结论 DNA修复酶基因XRCC1多态与NSCLC对GP方案化疗的敏感性有关,患者的基因型检测有可能作为预测NSCLC 对GP方案化疗敏感性的指标.     

XRCC1基因多态性与贲门癌的发病风险

目的通过病例-对照研究,探讨X-射线交错互补修复基因1(X-ray repair cross-complementing gene 1, XRCC1)基因多态性与贲门腺癌(gastric cardiac adenocarcinoma, GCA)发病风险的关系。方法采用聚合酶链反应 限制性片段长度多态性技术检测455例GCA 患者和650例对照人群XRCC1 Arg194Trp、Arg280His及Arg399Gln 3个多态性位点基因型和等位基因频率分布情况。结果XRCC1 Arg194Trp及Arg399Gln多态位点的基因型及等位基因型频率的分布在患者组和对照组之间无明显的差异（P>0.05）。但以吸烟和家族史状况分层分析发现,吸烟组中GCA患者280位点的His等位基因频率为11.5％,明显高于对照组8.2％,GCA患者组和健康对照组中Arg/Arg、Arg/His、His/His三种基因型频率分别是77.9％、21.2％、0.9％和84.9％、13.7％、1.4％,两组相比差异具有统计学意义（χ²=4.107,P=0.043）。与Arg/Arg基因型相比,携带His等位基因（Arg/His+His/His）可明显增高吸烟人群GCA的发病风险（OR=1.572, 95％CI=1.00~2.51）。结论本研究结果提示XRCC1基因Arg194Trp、Arg399Gln多态位点可能与GCA的发病风险无关,但Arg280His多态的His等位基因型可能增加吸烟人群GCA的发病风险。     

DNA修复酶XRCC1基因多态性与晚期肺癌化疗敏感性的关系研究

目的:研究DNA修复酶XRCC1基因codon194和codon399多态性与肺癌患者对铂类药物为基础的化疗敏感性的关系。方法:收集经病理学确诊的晚期肺癌112例,所有病例化疗前抽静脉血,提取白细胞DNA,用多聚酶链反应-限制性片段长度多态性(PCR-RFLP)分析技术检测XRCC1基因型。所有患者均经铂类药物为基础的化疗方案治疗。结果:(1)在肺癌患者中,XRCC1194Are/Arg、Arg/Trp和Trp/Trp基因型者分别为48例(43·3%)、51例(45·9%)和12例(10·8%);XRCC1399Arg/Arg、Arg/Gln、Gln/Gln基因型者分别为65例(58·0%)、36例(32·1%)和11例(9·8%)。经化疗后,51例患者有效,总有效率45·5%。(2)XRCC1194Trp/Trp基因型者的有效率为75·0%,显著高于Arg/Arg基因型者(37·5%,χ2=5·36,P=0·0206))。前者的化疗敏感性是后者的5倍(95%CI:1·03~27·21)。同时拥有XRCC1194Trp/Trp和XRCC1399Arg/Arg基因型者的有效率为80·0%,显著高于其他基因型者(P=0·0417,OR=5·40,95%CI:0·98~38·90)。结论:XRCC1基因多态性与晚期肺癌对铂类药物为基础的化疗敏感性相关,检测XRCC1基因型可以预测晚期肺癌化疗的敏感性。     

DNA损伤修复基因XRCC1和XPD遗传多态与晚期非小细胞肺癌对铂类药物的敏感性

目的 探讨DNA损伤修复基因XRCC1和XPD的遗传多态与晚期非小细胞肺癌（NSCLC）对以铂类为主化疗药物敏感性的关系。方法 以聚合酶链反应（PCR）结合限制性片段长度多态性（RFLP）,检测200例以顺铂（DDP）或卡铂（CBP）为主要化疗方案的NSCLC患者XRCC1 Arg194Trp和XPD Lys751Gln多态基因型,并比较不同基因型与化疗敏感性的关系。结果 化疗总有效（CR＋PR）率为36．0％,其中CR1例,PR71例,SD94例,PD34例。携带XRCC1第194位密码子Arg／Trp或Trp／Trp基因型的个体化疗敏感性是XRCC1第194位密码子Arg／Arg基因型携带者的2．48倍（95％CI为1．36～4．51,P=0．003）;未发现XPD Lys751Gln多态与化疗敏感性的相关性。联合分析这两个遗传多态发现,XRCC1 Arg194Trp和XPD Lys751Gln多态在NSCLC对铂类药物敏感性中存在一定的联合作用（趋势检验,P=0．004）。结论XRCC1 Arg194Trp和XPDLys751Gin遗传多态可能与NSCLC铂类药物敏感性有关。     

XRCC1单核苷酸多态与晚期非小细胞肺癌对铂类药物化疗敏感性的相关性

背景与目的DNA修复能力与肿瘤细胞对铂类药物的敏感性密切相关。本研究探讨DNA修复基因XRCC1单核苷酸多态性与非小细胞肺癌(non-smallcelllungcancer,NSCLC)患者对顺铂(cisplatin,DDP)或卡铂(carboplatin,CBP)为主的化疗方案敏感性的关系。方法经病理学确诊的晚期NSCLC患者105例,采用DDP或CBP为主的方案化疗,2～3个周期后进行临床疗效评价。以PCR-RFLP进行XRCC1Arg194Trp和Arg399Gln多态的基因分型,比较不同基因型对化疗敏感性的影响。比值比(OR)及其95%可信区间(CI)由logistic回归模型计算。结果携带至少一个Trp等位基因者化疗有效率为43.1%,显著高于携带Arg/Arg基因型的20.3%(OR=2.97,95%CI=1.15～7.72;P<0.05)。携带XRCC1399Arg/Arg基因型者化疗有效率为41.5%,显著高于携带至少一个Gln等位基因者的21.2%(OR=2.65,95%CI=1.03～6.87;P<0.05)。这两个多态之间存在联合作用,同时携带194Arg/Trp和399Arg/Arg基因型的患者,治疗有效率为66.7%,明显高于携带其它基因型的患者(有效率20.0%～23.1%)。结论XRCC1基因多态与NSCLC患者对铂类药物化疗的敏感性相关。     

ERCC1和XRCC1多态性与进展期非小细胞肺癌对铂类化疗的敏感性

目的探讨DNA修复基因ERCC1 118C/T和XRCC1 Arg194Trp多态性与进展期非小细胞肺癌(non-small cell lung cancer,NSCLC)患者铂类药物化疗敏感性的关系。方法采用PCR-RFLP技术检测149例经病理确诊的接受含铂两药方案化疗的NSCLC患者外周血ERCC1 118和XRCC1 194位点的基因型,并分析其与化疗疗效的关系。结果经2个周期化疗后,149例进展期NSCLC患者化疗有效率为32.9%。携带至少1个ERCC1 118T突变基因患者的化疗有效率至少是C/C野生型基因携带者的3倍(49.1%vs 23.4%,OR=3.156,95%CI:1.548～6.334,P=0.001)。携带至少1个XRCC1 194Trp突变基因患者的化疗有效率显著高于Arg/Arg基因型携带者(41.3%vs 23.2%,OR=2.326,95%CI:1.138～4.753,P=0.019)。ERCC1 118C/T和XRCC1 Arg194Trp 2个基因多态之间存在一定的联合作用,携带至少1个ERCC1 118 T突变基因同时又携带至少1个XRCC1 194Trp突变基因型者的化疗有效率明显高于同时携带ERCC1 118C/C和XRCC1 194Arg/Arg野生型基因者(66.7%vs 17.1%,OR=9.714,95%CI:3.104～30.406,P<0.001)。结论与单基因检测比较,2个基因的联合检测在预测铂类药物化疗敏感性中的价值更大。ERCC1 118和XRCC1 194基因多态联合与NSCLC患者对铂类药物化疗敏感性相关,ERCC1和XRCC1基因型的联合检测有可能成为预测铂类药物化疗敏感性的指标。     

XRCC1基因多态性与卵巢癌对铂类药物化疗敏感性的相关性研究

目的 探讨X线修复交叉互补基因1（XRCC1）Arg194Trp和Arg399Gln位点多态性与卵巢癌对铂类药物化疗敏感性之间的关系。方法 选取82例首次术后以铂类为基础化疗达6个周期的卵巢癌患者,采用聚合酶链反应 限制性片段长度多态性分析（PCR RFLP）检测外周血XRCC1 Arg194Trp和Arg399Gln位点的基因型,分别比较两个位点的不同基因型与化疗敏感性及两个位点之间的关系。结果 XRCC1 Arg194Trp存在3个基因型,即Arg／Arg、Arg／Trp、Trp／Trp,基因分布频率分别为47.6％、43.9％、8.5％;XRCC1 Arg399Gln亦存在3个基因型,即Arg／Arg、Arg／Gln、Gln／Gln,基因分布频率分别为25.6％、40.2％、34.1％。XRCC1 Arg399Gln 的不同基因型在FIGO分期和年龄分组中的差异均有统计学意义（P＜0.05）。化疗敏感组与不敏感组两个位点多态性基因型之间的差异均有统计学意义（P＜0.05）。XRCC1 Arg194Trp的Trp／Trp和Arg 399Gln的Gln/Gln基因型比Arg／Arg基因型更易对铂类药物产生耐药性,比值比分别增加至13.50倍（95％CI：1.461～124.739）和7.65倍（95％CI：2.012～29.088）。同时携带Arg194Trp Arg／Trp和Arg399Gln Gln／Gln基因型的患者对化疗不敏感率高达84.62％（OR=22.00,95％CI：2.534～190.998;P＜0.05）。结论 XRCC1 Arg194Trp和Arg399Gln位点基因多态性与卵巢癌对铂类药物的化疗敏感性相关,并且两位点之间存在联合效应。     

XRCC1和XRCC3单核苷酸多态性与晚期非小细胞肺癌铂类药物化疗疗效的相关性

背景与目的 DNA修复基因多态性预测铂类药物化疗敏感性对非小细胞肺癌(non-small cell lung cancer,NSCLC)个体化治疗具有重要意义.本研究旨在探讨X线修复交错互补基因1(X-ray repair cross complementing gene 1,XRCC1)和X线修复交错互补基因3(X-ray repair cross complementing gene 3,XRCC3)单核苷酸多态性与晚期NSCLC患者对铂类药物化疗疗效的关系.方法 采用PCR-RFLP方法检测130例以含铂方案化疗的晚期NSCLC患者外周血DNA中XRCC1 Arg194 Trp、Arg399 Gln和XRCC3 Thr241 Met基因多态性,分析其基因型与化疗疗效的关系.结果 130例晚期NSCLC患者采用含铂方案化疗2个周期后,化疗总有效率为33.8％.XRCC1 194和399基因多态性与铂类药物化疗敏感性相关,而XRCC3 241基因多态性与化疗敏感性无关(P=0.145).携带至少1个XRCC1 194 Trp等位基因者化疗有效率至少是携带Arg/Arg基因型患者的2.5倍(42.1％vs22.2％,OR=2.545,95％CI:1.159-5.590,P=0.020).携带XRCC1399 Arg/Arg基因型者的化疗有效率为45.5％,明显高于携带至少1个Gln等位基因者(21.9％)(OR=0.336,95％CI:0.156-0.722,P=0.005).XRCC1 194和399基因多态性之间存在联合作用,同时携带至少1个XRCC1 194 Trp等位基因和399 Arg/Arg基因型者的化疗有效率明显高于同时携带194 Arg/Arg和399 Arg/Gln基因型者(44.4％ vs 18.8％,OR=3.467,95％CI:1.223-9.782,P=0.019).XRCC1和XRCC3基因多态性在化疗敏感性方面存在一定的联合作用,携带至少1个XRCC1 194 Trp等位基因和399 Arg/Arg野生型基因同时又携带XRCC3 241 Thr/Met基因型者的化疗有效率明显高于其它基因型携带者.结论 XRCC1和XRCC3的多态联合可能与晚期NSCLC患者对铂类药物化疗疗效具有相关性.     

Genetic polymorphisms of DNA repair genes XRCC1 and XRCC3 and risk of colorectal cancer in Chinese population

Aim: The distribution of DNA repair gene XRCC1 and XRCC3 genotypes was used to assess the potential influence of genetic polymorphisms on risk of colorectal cancer, and interactions with other factors. Methods: a 1:2 matched case-control study was conducted with 485 cases and 970 controls. XRCC1 and XRCC2 genotype polymorphisms were based upon duplex polymerase-chain-reaction with the confronting-two-pairprimer (PCR-CTPP) method. Results:The XRCC1 399Cln allele polymorphism was found to be associated with an increased colorectal cancer risk, while an non-significant inversely association was noted for XRCC3 241Thr/Thr genotype. We also found that individuals with the XRCC1 399 Gln and XRCC3 241Met alleles had an elevated risk, while XRCC3241Thr/Thr was proctective. Conclusion: This study is the first to provide evidence of importance of XRCC1 and XRCC3 gene polymorphisms for risk of colorectal cancer in the Chinese population.     

非小细胞肺癌NP方案化疗敏感性与DNA修复基因XRCC1多态性的关系

背景与目的:基因多态预测肿瘤化疗药物敏感性对肿瘤个体化治疗具有重要意义。本研究旨在探讨DNA修复基因XRCC1 codon194及399位点基因多态性与非小细胞肺癌长春瑞滨加顺铂(vinorelbine and cisplatin,NVB and DDP,NP)方案化疗敏感性的关系。方法:采用聚合酶链反应-限制性片段长度多态性技术检测164例非小细胞肺癌患者外周血DNAXRCC1194和399位点的多态性。选择NP方案化疗,化疗两周期后评价疗效,并分析化疗敏感性与基因多态性的关系。结果:携带XRCC1基因Codon194C/T+T/T基因型者化疗有效率(41.8%)是C/C基因型者(26.0%)的2.038倍(P=0.036,95%CI=1.044-3.976)。携带XRCC1基因Codon399G/G、A/G、A/A型的患者化疗有效率(37.1%,34.6%,14.3%)之间的差异无统计学意义(P>0.05)。应用分析软件SHEsis发现以     

DNA Repair Gene Polymorphisms Do Not Predict Response to Radiotherapy-Based Multimodality Treatment of Patients with Rectal Cancer: a Meta-analysis

Background: : A number of association studies have been carried out to investigate the relationship betweengenetic polymorphisms in DNA repair genes and response to radiotherapy-based multimodality treatment ofpatients with rectal cancer. However, their conclusions were inconsistent. The objective of the present study wasto assess the role of DNA repair gene genetic polymorphisms in predicting genetic biomarkers of the response inrectal cancer patients treated with neoadjuvant chemoradiation. Materials and Methods: Studies were retrievedby searching the PubMed database, Cochrane Library, Embase, and ISI Web of Knowledge. We conducted ameta-analysis to evaluate the association between genetic polymorphisms and the response in rectal cancer treatedwith neoadjuvant chemoradiation by checking odds ratios (ORs) and 95% confidence intervals (CIs). Results:Data were extracted from 5 clinical studies for this meta-analysis. The results showed that XRCC1 RS25487,XRCC1 RS179978, XRCC3 RS861539, ERCC1 RS11615 and ERCC2 RS13181 were not associated with theresponse in the radiotherapy-based multimodality treatment of patients with rectal cancer (p>0.05). Conclusions:This study shows that DNA repair gene common genetic polymorphisms are not significantly correlated withthe radiotherapy-based multimodality treatment in rectal cancer patients.     

XRCC1基因多态性与肺癌易感性关系的研究进展

X射线损伤修复的交叉互补基因 (X rayrepaircrosscomplementinggroup 1,XRCC1)是一种DNA损伤修复基因 ,其多态性能够改变DNA修复功能和效率 ,影响肿瘤易感性。分析了XRCC1基因结构、功能及其多态性与肺癌易感性的关系     

DNA修复基因XRCC1多态性与肺癌易感性的关系

目的:研究碱基切除修复基因XRCC1多态性与肺癌易感性的关系。方法:采用病例-对照研究,收集太原市原发性肺癌患者111例为病例组,同时随机抽取210名健康居民作为对照组,并进行流行病学调查。应用PCR-RFLP方法分析由内切酶MspI识别XRCC1基因Arg399Gln位点的多态性,比较不同基因型与肺癌易感性的关系,以及基因多态性与吸烟之间对肺癌易感性的交互作用。结果:XRCC1密码子399杂合基因型Arg/Gln可能对鳞癌有较弱的保护效应,并可能降低吸烟者患肺癌的危险性。而纯合突变基因型Gln/Gln与和吸烟的存在协同作用可显著提高肺癌的危险度。结论:碱基切除修复基因XRCC1密码子399的多态性可能会对肺癌易感性产生影响,并可能与吸烟量之间存在一定的协同作用。     

Predictive value of XRCC1 and XRCC3 gene polymorphisms for risk of ovarian cancer death after chemotherapy

Objective: To investigate any association between XRCC1 and XRCC3 polymorphisms and outcome ofplatinum-based chemotherapy in ovarian cancer patients. Methods: With a prospective study design was caseswere consecutively collected from January 2005 to January 2007. All 310 included patients were followed-upuntil the end of January 2010. Genotyping of XRCC1 and XRCC3 polymorphisms was conducted by TaqManGene Expression assays. Results: A total of 191 patients died during follow-up. Our study showed a lowersurvival rate in XRCC1 399 Arg/Arg genotype than Gln/ Gln, with a significant increased risk of death (HR=1.69,95%CI=1.07-2.78). Similarly, those carrying XRCC3 Thr/ Thr genotype had a increased risk as compare tothe Met/Met genotype, with a HR (95% CI) of 1.90 (1.12-3.41). There was no significant association betweenXRCC1 Arg194Trp and XRCC1Arg280His gene polymorphisms and ovarian cancer death. Conclusion: Ourstudy demonstrates that polymorphisms in DNA repair genes have roles in the susceptibility and survival ofovarian cancer patients.     

Variation in DNA repair genes ERCC2, XRCC1, and XRCC3 and risk of follicular lymphoma.

The reasons for the positive association between skin cancer and non-Hodgkin's lymphoma are not known but may be due to common susceptibility involving suboptimal DNA repair. Therefore, we investigated selected polymorphisms and haplotypes in three DNA repair genes, previously associated with skin cancer and DNA repair capacity, in risk of follicular lymphoma, including possible gene interaction with cigarette smoking and sun exposure. We genotyped 19 single nucleotide polymorphisms (SNP) in the ERCC2, XRCC1, and XRCC3 genes in 430 follicular lymphoma patients and 605 controls within a population-based case-control study in Denmark and Sweden. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated using unconditional logistic regression and haplotype associations were assessed with a global score test. We observed no associations between variation in the ERCC2 and XRCC1 genes and follicular lymphoma risk. In XRCC3, increased risk of follicular lymphoma was suggested for rare homozygotes of three SNPs [Rs3212024: OR, 1.8 (95% CI, 1.1-2.8); Rs3212038: OR, 1.5 (95% CI, 1.0-2.4); Rs3212090: OR, 1.5 (95% CI, 1.0-2.5)]. These results were strengthened in current cigarette smokers. However, evidence of differences in XRCC3 haplotype distributions between follicular lymphoma cases and controls was weak, both overall and in current smokers. We conclude that polymorphic variation in the XRCC3 gene, but not in ERCC2 or XRCC1, may be of importance for susceptibility to follicular lymphoma, perhaps primarily in current smokers. The link between skin cancer and follicular lymphoma is unlikely to be mediated through common variation in the studied DNA repair gene polymorphisms.     

Polymorphism of the DNA Repair Gene XRCC1 (Arg194Trp) and its role in Colorectal Cancer in Kashmiri Population: a Case Control Study

Background: Genetic polymorphisms in DNA repair genes may influence individual variation in DNArepair capacity, which may be associated with risk of developing cancer. For colorectal cancer the importanceof mutations in mismatch repair genes has been extensively documented. Materials and Methods: In this studywe focused on the Arg194Trp polymorphism of the DNA repair gene XRCC1, involved in base excision repair(BER) and its role in colorectal cancer in Kashmiri population. A case-control study was conducted including100 cases of colorectal cancer, and 100 hospital-based age- and sex-matched healthy controls to examine the roleof XRCC1 genetic polymorphisms in the context of colorectal cancer risk for the Kashmiri population. Results:Genotype analysis of XRCC1 Arg194Trp was conducted with a restriction fragment length polymorphism (RFLP)method. The overall association between the XRCC1 polymorphism and the CRC cases was found to be significant(p < 0.05) with both the heterozygous genotype (Arg/Trp) as well as homozygous variant genotype (Trp/Trp)being moderately associated with the elevated risk for CRC [OR=2.01 (95% CI=1.03-3.94) and OR=5.2(95%CI=1.42-19.5)] respectively. Conclusions: Our results suggest an increased risk for CRC in individuals withXRCC1 Arg194Trp polymorphism suggesting BER repair pathway modulates the risk of developing colorectalcancer in the Kashmiri population.