XRCC1单核苷酸多态性预测晚期NSCLC铂类药物化疗的敏感性

目的研究XRCC1单核苷酸多态性与晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)对以顺铂(cisplatin,DDP)或卡铂(carboplatin,CBP)为基础药物的化疗敏感性的关系。方法经病理学确诊的晚期NSCLC患者97例,采用DDP或CBP为基础药物的方案化疗,3个周期后进行疗效评价。以聚合酶链反应(PCR)结合限制性片段长度多态性(RFLP)检测XRCC1Arg194Trp和Arg399Gln基因型,并比较基因型与化疗敏感性的关系。结果(1)携带XRCC1194Arg/Trp的患者有效率高于携带Arg/Arg、Trp/Trp基因型的患者(P<0.05);携带至少一个Trp等位基因基因型患者的化疗敏感性是携带Arg/Arg基因型的3.4倍(OR=3.39,95%,CI=1.32~8.70,P<0.05)。(2)携带XRCC1399Arg/Arg、Arg/Gln、Gln/Gln基因型患者的有效率分别为36.4%、22.9%、28.6%,差异无统计学意义(P>0.05)。尚未发现XRCC1Arg194Trp和Arg399Gln基因多态性存在联合作用。结论XRCC1Arg194Trp单核苷酸多态性可能与晚期NSCLC对铂类药物的化疗敏感性相关。     

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。     

XRCC1 单核苷酸多态性预测晚期NSCLC铂类药物化疗的敏感性

 目的 研究XRCC1单核苷酸多态性与晚期非小细胞肺癌（nowsmallcelllungcancer，NSCLC）对以顺铂（cisplatin，DDP）或卡铂（carDoplatin，CBP）为基础药物的化疗敏感性的关系。方法 经病理学确诊的晚期NSCLC患者97例，采用DDP或CBP为基础药物的方案化疗，3个周期后进行疗效评价。以聚合酶链反应（PCR）结合限制性片段长度多态性（RFLP）检测RiCelArg194Trp和Arg399G1n基因型，并比较基因型与化疗敏感性的关系。结果 （1）携带RiCel194Arg／Trp的患者有效率高于携带Arg／Arg、Trp／Trp基因型的患者（P〈0．05）；携带至少一个Trp等位基因基因型患者的化疗敏感性是携带Arg／Arg基因型的3．4倍（OR=3．39，95％，CI=1．3248．70，P〈0.05）。（2）携带RiCel399Arg／Arg、Arg／G1n、Gin／Gin基因型患者的有效率分别为36．4％、22．9％、28．6％，差异无统计学意义（P〉0.05）。尚未发现RiCelArg194Trp和Arg399Gln基因多态性存在联合作用。结论 XRCClArg194Trp单核苷酸多态性可能与晚期NSCLC对铂类药物的化疗敏感性相关。     

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。     

碱基切除修复基因多态性与晚期非小细胞肺癌铂类药物化疗敏感性

目的：探讨DNA碱基切除修复通路中XRCC1 Arg399Gln和ADPRT Val762Ala基因多态性与晚期非小细胞肺癌（NSCLC）铂类药物化疗敏感性的关联,并与先前报道的XRCC1 T-77C、Argl94Trp联合分析其预测作用。方法：收集接受铂类药物为基础化疗的晚期NSCLC患者107例,用PCR—RFLP法检测基因型,分析各基因型与铂类药物化疗有效率的关联,并以非条件Logistic回归模型对患者年龄、性别、病理类型、临床分期和治疗方案进行校正。结果：对XRCC1 Arg399Gln多态性进行单因素分析时,发现携带至少1个Gln等位基因的患者的化疗有效率是携带Arg／Arg基因型者的0．42倍（95％CI：0．19—0．93）,差异具有统计学意义;经多因素校正后发现携带至少1个Gln等位基因的患者的化疗有效率是携带Arg／Arg基因型者的0．52倍（95％CI：0．22—1．26）,但差异不再具有统计学意义。对ADPRT Val762Ala多态性进行多因素分析时,发现携带至少1个Ala等位基因的患者的化疗有效率是携带Val／Val基因型者的1．57倍（95％CI：0．67—3．66）。联合分析各患者4个多态性位点的铂类药物敏感基因型的总数目与铂类药物化疗有效率的关联,并经多因素分析校正后,发现携带3—4个铂类药物敏感基因型的患者的化疗有效率是具有0—2个铂类药物敏感基因型者的4．15倍（95％CI：1．54—11．19）,差异具有统计学意义。结论：XRCC1 Arg399Gln多态性与铂类药物化疗敏感性的关系需进一步确认,似乎携带野生型Arg／Arg者对铂类药物化疗更敏感;但未能发现ADPRT Val762Ala多态性与锥苑矧别眇德魄牲存在明显关联;4个多态性位点联合分析的预测效能高于单个位点。     

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。     

DNA修复基因多态性与肺癌顺铂化疗敏感性的研究

目的:研究切除修复交叉互补基因1(excision repair cross-complementing gene 1,ERCC1)Asn118Asn、切除修复交叉互补基因2(excision repair cross-complementing gene 2,ERCC2)Lys751Gln和X线修复交叉互补基因1(X-ray repair cross complementing group 1,XRCC1)Arg399Gln单核苷酸多态性与非小细胞肺癌(non-small cell lung cancer,NSCLC)对铂类药物化疗敏感性的相关性。方法:采用基因测序的方法,检测89例以铂类药物为主要化疗方案的NSCLC患者外周血DNA中ERCC1基因Asn118Asn、ERCC2基因Lys751Gln和XRCC1基因Arg399Gln的基因型;采用统计学方法分析不同基因型与化疗疗效的相关性。结果:89例NSCLC患者采用铂类药物化疗总有效率为29.2%;ERCC1基因Asn118Asn和ERCC2基因Lys751Gln基因型在化疗有效组和无效组之间的分布,差异无统计学意义(P>0.05);而携带XRCC1基因Arg399Arg与携带至少1个Gln等位基因(Arg399Gln和Gln399Gln)基因型患者的有效率分别为76.9%和23.1%(χ2=11.1,P=0.001)。携带XRCC1基因Arg399Arg基因型患者对化疗的敏感性明显高于携带至少1个Gln等位基因型的患者(比值比为5.228,95%可信区间为1.776～15.387,P=0.003)。ERCC1、ERCC2和XRCC1基因型的联合可以提高化疗的有效率。结论:ERCC1、ERCC2和XRCC1基因的单核苷酸多态性的联合可能与NSCLC对铂类药物化疗敏感性具有相关性。     

碱基切除修复基因多态性与晚期非小细胞肺癌铂类药物化疗敏感性

目的:探讨DNA碱基切除修复通路中XRCC1 Arg399Gln和ADPRT Val762Ala基因多态性与晚期非小细胞肺癌(NSCLC)铂类药物化疗敏感性的关联,并与先前报道的XRCC1 T-77C、Argl94Trp联合分析其预测作用.方法:收集接受铂类药物为基础化疗的晚期NSCLC患者107例,用PCR-RFLP法检测基因型,分析各基因型与铂类药物化疗有效率的关联,并以非条件Logistic回归模型对患者年龄、性别、病理类型、临床分期和治疗方案进行校正.结果:对XRCC1 Arg399Gln多态性进行单因素分析时,发现携带至少1个Gln等位基因的患者的化疗有效率是携带Arg/Arg基因型者的0.42倍(95%CI:0.19-0.93),差异具有统计学意义;经多因素校正后发现携带至少1个Gln等位基因的患者的化疗有效率是携带Arg/Arg基因型者的0.52倍(95%CI:0.22-1.26),但差异不再具有统计学意义.对ADPRT Val762Ala多态性进行多因素分析时,发现携带至少1个Ala等位基因的患者的化疗有效率是携带Val/Val基因型者的1.57倍(95%CI:0.67-3.66).联合分析各患者4个多态性位点的铂类药物敏感基因型的总数目与铂类药物化疗有效率的关联,并经多因素分析校正后,发现携带3-4个铂类药物敏感基因型的患者的化疗有效率是具有0-2个铂类药物敏感基因型者的4.15倍(95%CI:1.54-11.19),差异具有统计学意义.结论:XRCC1 Arg399Gln多态性与铂类药物化疗敏感性的关系需进一步确认,似乎携带野生型Arg/Arg者对铂类药物化疗更敏感;但未能发现ADPRTVal762Ala多态性与铂类药物化疗敏感性存在明显关联;4个多态性位点联合分析的预测效能高于单个位点.     

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。     

Prognostic Significance of GSTP1, XRCC1 and XRCC3 Polymorphisms in Non-small Cell Lung Cancer Patients

Aim: Individual differences in chemosensitivity and clinical outcome in non-small cell lung cancer (NSCLC)patients treatment with platinum-based chemotherapy may be due to genetic factors. Our study aimed toinvestigate the prognostic role of GSTP1, XRCC1 and XRCC3 in NSCLC patients treated with chemotherapy.Methods: A total of 460 cases were consecutively selected from The Affiliated Hospital of Nantong Universitybetween Jan. 2003 to Nov. 2006, and all were followed-up until Nov. 2011. Genotyping of GSTP1 Ile105Val, XRCC1Arg194Trp, XRCC1 Arg399Gln and XRCC3 Thr241Met was conducted by duplex polymerase-chain-reactionwith confronting-two-pair primer methods. Results: Patients with GSTP Val/Val exhibited a shorter survivaltime, and had a 1.89 fold greater risk of death than did those with the IIe/IIe genotype. For XRCC1 Arg194Trp,the variant genotype Trp/Trp was significantly associated with a decreased risk of death from NSCLC whencompared with the Arg/Arg. Individuals carrying XRCC1 399Gln/Gln genotype had a longer survival time,with a lowered risk of death from NSCLC. Conclusion: This study indicated that GSTP1 Ile105Val, XRCC1Arg194Trp and XRCC1Arg399Gln genes have a role in modifying the effect of platinum-based chemotherapyfor NSCLC patients in a Chinese population. Our findings provide information for therapeutic decisions forindividualized therapy in NSCLC cases.     

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.     

Polymorphisms in DNA repair gene XRCC1 and increased genetic susceptibility to glioma

Background: The XRCC1 gene encodes the XRCC1 protein, which complexes with three other DNA repair enzymes involved in the base-excision repair (BER) pathways. Different XRCC1 polymorphisms may increase the risk of cancers by impairing interaction with other enzymatic proteins and consequently altering DNA repair activity, and result in carcinogenesis. Our study aimed to investigate any association between three polymorphisms of the XRCC1 gene at codon 194, 280 and 399 and potential glioma risk. Methods: We collected 127 patients with primary glioma and 249 controls who requested general health examinations from Union Hospital of Tongji Medical College hospital from March 2007 to September 2010. A total of 5 ml venous blood was drawn from each subject. The polymorphisms of XRCC1 gene at codons 194, 280 and 399 were analyzed based on duplex polymerase-chain-reactions with the confronting-two-pair primer (PCR-CTPP) method. Results: The homozygous Trp/Trp and heterozygotes Arg/Trp variants of codon 194 had a 2.12 fold and 1.46 fold increased risk of glioma compared to the homozygous Arg/Arg wide genotypes. The same effect was found in codon 399, the codon 399 Gln/Gln and Arg/Gln genotypes being associated with a 2.24 fold and 1.67 fold increased risk in glioma. When comparing the codon 194 Arg/Arg and 399 Arg/Arg genotypes, the combination of codon 194 Trp allele and 399 Gln allele had a heavy increase in glioma risk (OR=2.87, 95%CI=1.56-6.73). Conclusion: The present study provided evidence of a potential role for XRCC1 codon 194 and 399 polymorphisms in genetic predisposition to glioma among the Chinese population. This analysis of correlation of DNA repair genes and glioma may provide a deeper insight into the genetic and environment factors for cancer risk.     

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.     

Prediction Value of XRCC 1 Gene Polymorphism on the Survival of Ovarian Cancer Treated by Adjuvant Chemotherapy

Objective: We conducted a prospective study to test the association between three amino acid substitutionpolymorphismic variants of DNA repair genes, XRCC1 (Arg194Trp), XRCC1(Arg280His) and XRCC1(Arg399Gln), and clinical outcome of ovarian cancer patients undergoing adjuvant chemotherapy. Methods:195 patients with primary advanced ovarian cancer and treated by adjuvant chemotherapy were included in ourstudy. All were followed-up from Jan. 2007 to Jan. 2012. Genotyping of XRCC1 polymorphisms was conductedby TaqMan Gene Expression assays. Results: The XRCC1 194 Trp/Trp genotype conferred a significant riskof death from ovarian cancer when compared with Arg/Arg (HR=1.56, 95%CI=1.04-3.15). Similarly, thosecarrying the XRCC1 399 Gln/Gln genotype had a increased risk of death as compared to the XRCC1 399Arg/Arg genotype with an HR (95% CI) of 1.98 (1.09-3.93). Conclusion: This study is the first to provide evidencethat XRCC1 gene polymorphisms would well be useful as surrogate markers of clinical outcome in ovariancancer cases undergoing adjuvant chemotherapy.     

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.