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。     

ERCC1和XRCC1基因多态性与接受奥沙利铂化疗晚期大肠癌患者生存期的关系

目的: 探讨DNA损伤修复基因ERCC1 Asn118Asn和XRCC1 Arg399Gln多态性与接受奥沙利铂一线化疗的中国晚期大肠癌患者生存期的关系。 方法: 99例晚期大肠癌患者化疗前抽取静脉血并提取DNA,以real-time PCR法对ERCC1、XRCC1基因进行SNP分型。患者接受奥沙利铂为主的化疗方案化疗,比较不同基因型与患者生存期的关系。 结果: ERCC1 Asn118Asn基因位点在所研究的中国大肠癌患者中的突变频率为:C/C50.51%、C/T41.41%、T/T8.08%;XRCC1 Arg399Gln基因突变频率为:G/G52.53%、G/A38.38%、A/A9.09%。99例晚期大肠癌患者中位TTP为7个月。ERCC1C/C基因型患者中位TTP10个月,C/T+T/T型患者中位TTP5个月,二者有显著统计学差异(P<0.01);XRCC1G/G基因型中位TTP10个月,G/A+A/A基因型中位TTP5个月,二者比较差异有显著性(P<0.01)。两个基因联合多态性分析发现,同时携带ERCC1C/C和XRCC1G/G基因型、ERCC1C/C和XRCC1G/A+A/A基因型、ERCC1C/T+T/T和XRCC1G/G基因型、以及ERCC1C/T+T/T和XRCC1G/A+A/A基因型的患者中位TTP分别为11个月、6个月、5个月和5个月,4组比较差异有显著性(P<0.01)。 结论: ERCC1 Asn118Asn、XRCC1 Arg399Gln基因多态性与中国晚期大肠癌患者接受奥沙利铂一线化疗后的生存期有关。     

ERCC1和XRGC1基因多态性与接受奥沙利铂化疗晚期大肠癌患者生存期的关系

目的：探讨DNA损伤修复基因ERCC1 Asn118Asn和XRCC1 Arg399Gln多态性与接受奥沙利铂一线化疗的中国晚期大肠癌患者生存期的关系。方法：99例晚期大肠癌患者化疗前柚取静脉血并提取DNA，以real-time PCR法对ERCC1、XRCC1基因进行SNP分型。患者接受奥沙利铂为主的化疗方案化疗，比较不同基因型与患者生存期的关系。结果：ERCC1 Asn118Asn基因位点在所研究的中国大肠癌患者中的突变频率为：C／C50．51％、C／T41．41％、T/T 8．08％；XRCC1 Arg399Gln基因突变频率为：G／G52．53％、G／A38．38％、A／A9．09％。99例晚期大肠癌患者中位TTP为7个月。ERCC1C／C基因型患者中位TTP 10个月，C/T＋T/T型患者中位TTP 5个月，二者有显著统计学差异（P〈0．01）；XRCC1G／G基因型中位TTP 10个月，G／A＋A／A基因型中位TTP 5个月，二者比较差异有显著性（P〈0．01）。两个基因联合多态性分析发现，同时携带ERCC1C／C和XRCC1G／G基因型、ERCC1C／C和XRCClG／A＋A／A基因型、ERCC1C／T＋唧和XRCC1G／G基因型、以及ERCC1 C／T＋T/T和XRCC1G／A＋A／A基因型的患者中位TTP分别为11个月、6个月、5个月和5个月，4组比较差异有显著性（／9〈0．01）。结论：ERCC1 Asn118Asn、XRCC1 Arg399Gln基因多态性与中国晚期大肠癌患者接受奥沙利铂一线化疗后的生存期有关。     

汉族晚期大肠癌ERCC1和XRCC1基因多态性与奥沙利铂化疗敏感相关性的研究

目的:探讨ERCC1Asn118Asn和XRCC1Arg399Gln多态性与中国汉族晚期大肠癌患者对奥沙利铂(Oxaliplatin,L-OHP)一线化疗临床效果的关系。方法:62例晚期大肠癌患者化疗前抽取静脉血并提取DNA,以RT-PCR法对ERCC1、XRCC1基因进行SNP分型。患者接受奥沙利铂为主的化疗方案化疗,比较不同基因型与化疗效果的关系。结果:ERCC1Asn118Asn基因突变频率为:C/C53.23%(33/62),C/T37.10%(23/62),T/T9.67%(6/62);XRCC1Arg399Gln基因突变频率为:G/G50.00%(31/62),G/A37.10%(23/62),A/A12.90%(8/62)。62例患者化疗2～3个周期后评价临床获益率为54.84%。ER-CC1基因Asn118Asn基因型C/C与C/T T/T在化疗获益组和化疗不敏感组中分布差异有统计学意义,χ2=6.289,P=0.021。XRCC1基因Arg399Gln基因型G/G与G/A A/A在化疗获益组和化疗不敏感组中分布差异也有统计学意义,χ2=6.513,P=0.021。两者联合多态性分析发现,同时携带ERCC1C/C和XRCC1G/G基因型患者化疗敏感性是同时携带ERCC1C/T T/T和XRCC1G/A A/A基因型患者的11.333倍,P=0.002。结论:ERCC1Asn118Asn、XRCC1Arg399Gln基因多态性与中国汉族晚期大肠癌患者接受奥沙利铂一线化疗后的临床效果有关。     

ERCC1和XRCC3基因多态性在接受含铂方案化疗NSCLC中的疗效预测作用

[目的]探讨DNA修复基因ERCC1 118和XRCC3 241多态性对于接受一线含铂化疗方案的非小细胞肺癌（NSCLC）患者的疗效预测作用。[方法]130例晚期接受含铂化疗的NSCLC患者进入研究．应用Taqman探针结合实时荧光PCR方法分析其外周血基因多态性．分析ERCC1 118和XRCC3 241多态性与疗效、疾病进展时间和总体生存期之间的关系。[结果]130例患者的总体有效率为20％．中位生存时间为15个月．ERCC1 118和XRCC3 241多态性与疗效无显著相关性。ERCC1 118基因型C/T或T/T患者的生存时间显著延长（P=0.003）。Cox多因素分析显示,ERCC1 118基因型C/T或T/T以及化疗有效患者的生存期显著延长。[结论]DNA修复基因ERCC1 118基因型C／T或T/T多态性可以延长NSCLC患者铂类治疗后的生存时间．     

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。     

X 线交错互补修复基因多态性与晚期胃癌患者对DDP 化疗疗效的相关性研究*

目的:本研究旨在观察X 线交错互补修复基因（XRCC1399）多态性与以DDP 为基础的化疗方案治疗晚期胃癌的疗效间的关系。方法:收集经病理确诊的晚期胃癌59例。所有晚期胃癌病例化疗前抽取外周血,提取脱氧核糖核酸（DNA）,用连接酶检测反应技术检测研究对象的XRCC1399基因型。所有患者经多西他赛（Docetaxel ）+ 5- 氟尿嘧啶（5-FU ）+ 顺铂（DDP ）联合方案化疗,化疗后观察疗效及其与XRCC1399基因多态性之间的关系。结果:59例晚期胃癌患者中,16例（27.12%）为A/A 基因型,18例（30.51%）为G/A 基因型,25例（42.37%）为G/G 基因型。其中,4 例完全缓解（CR）,14例为部分缓解（PR）,19例稳定（SD）,22例进展（PD）,总化疗有效率为30.51% 。XRCC1399A/A 基因型患者的化疗有效率（68.75%）明显高于G/A 基因型患者（22.23%）,P<0.01,明显高于G/G 基因型患者（12.0%）,P<0.01。G/A 基因型患者的化疗有效率与G/G 基因型患者之间无显著性差异,P>0.05。结论:XRCC1399基因型对预测以DDP 为基础的化疗方案治疗晚期胃癌的疗效具有较好的临床意义,XRCC1399A/A 基因型的晚期胃癌患者对以DDP 为主的化疗方案较为敏感。      

DNA修复基因多态性影响晚期胃癌卡培他滨联合奥沙利铂化疗的临床预后

目的:探讨DNA修复基因(ERCC1、ERCC2、XRCC1)单核苷酸多态性对胃癌患者卡培他滨联合奥沙利铂化疗敏感性的相关性.方法:本回顾性研究选取XELOX作为一线化疗方案的100例晚期胃癌患者为研究对象,检测分析三个基因六个单核苷酸多态性位点(ERCC1 rs11615;ERCC2 rs13181,rs1799793;XRCC1 rs25487,rs25489,rs1799782),同时分析其与临床预后的关系.结果:XRCC1 rs25487的A/G等位基因频率、AG/AA/GG基因分布频率均与疾病化疗敏感性和无进展生存期有关,携带GG基因型患者疗效好(P<0.05),中位PFS为8.00个月(95%CI:6.34~9.66);ERCC2 rs13181的G/T等位基因频率、GG/GT/TT基因分布频率与疾病化疗敏感性和无进展生存期明显相关,携带TT基因型患者疗效好(P<0.05),中位PFS为7.46个月(95%CI:6.45~8.48).COX比例风险模型显示ERCC2 rs13181 G/T基因型是晚期胃癌无进展生存期的独立风险因素之一(HR=0.72,95%CI:0.53~0.97,P=0.025).结论:ERCC2 rs13181基因多态性可能是评估接受XELOX化疗晚期胃癌患者预后的关键指标.     

XRCC1单核苷酸多态性与含铂类药物化疗对肝肾功能影响相关性分析

目的探讨X射线损伤修复交叉互补基因1单核苷酸（XRCC1）多态性与恶性肿瘤患者铂类药物化疗前后肝肾功能变化的关系。方法化疗前采集外周静脉血,采用多聚酶链反应一高温连接酶反应（PCR—LDR）,进行XRCC1 Arg399Gln基因多态性的分型,观察化疗前后患者胆红素、转氨酶、蛋白、GGT、碱性磷酸酶、尿素氮、肌酐、尿酸等多项指标改变情况。结果携带XRCC1 399 Gln/Gln基因型患者,含铂类药物化疗前后总蛋白量的改变幅度低于XRCC1 399 Arg/Gln和XRCC1 399 Arg/Arg者;携带XRCC1 399 Arg/Gln基因型患者,含铂类药物化疗前后尿酸的变化高于XRCC1 399 Gln/Gln和XRCC1 399 Arg/Arg者;含铂类药物化疗前后其余各项肝肾功能指标的变化与XRCC1 Arg 399Gln单核苷酸多态性无关。结论 XRCC1单核苷酸多态性与含铂类药物化疗前后肝肾功能的改变无明显相关性。     

晚期大肠癌ERCC5基因启动子-763A〉G多态性与铂类药物疗效相关性的研究

目的：探讨ERCC5基因启动子区单核苷酸多态性与中国汉族晚期大肠癌奥沙利铂疗效的相关性。方法：收集以奥沙利铂为主化疗的105例晚期大肠癌患者化疗开始前静脉血,提取基因组DNA,应用PCR-LDR方法检测ERCC5基因3个SNP位点-1415C〉T（rs2094258）-7、63A〉G（rs2016073）及-413C〉T（rs943245）多态性,分析不同基因型与疾病控制率、无进展生存期（PFS）的相关性。结果：携带ERCC5-763GG-、763AG和-763AA基因型的患者化疗疾病控制率分别为86.7%、69.2%和52.6%,其中携带-763GG基因型的患者疾病控制率显著高于携带-763AA基因型的患者,P=0.028。携带-763AA基因型的患者中位PFS（36/95例,6个月）低于携带-763AG基因型（48/95例,8个月）及携带-763GG基因型（11/95例,10个月）的患者,差异有统计学意义,χ^2=9.205,P=0.002。-1415C〉T多态性与化疗疾病控制率和PFS之间均无显著相关性。-413C〉T位点未发现遗传多态。结论：ERCC5启动子区-763A〉G单核苷酸多态性与晚期大肠癌奥沙利铂临床疗效相关。     

晚期非小细胞肺癌ＧＳＴＰ１、ＸＲＣＣ１基因多态性与铂类药物疗效的关系

目的　探讨谷胱甘肽Ｓ转移酶Ｐ１（ＧＳＴＰ１）和Ｘ线修复交叉互补基因１（ＸＲＣＣ１）基因多态性与晚期非小细胞肺癌（ＮＳＣＬＣ）患者化疗疗效的关系。方法　经病理学确诊的晚期ＮＳＣＬＣ患者９４例,化疗前取静脉血采用ＤＮＡ测序法检测ＧＳＴＰ１和ＸＲＣＣ１基因多态性,给予铂类为主方案化疗（顺铂７５ｍｇ／ｍ２,ｄ１）,２～３周期后评价疗效,记录疾病进展时间（ＴＴＰ）,分析ＧＳＴＰ１和ＸＲＣＣ１基因多态性与化疗疗效的关系。结果　在９４例晚期ＮＳＣＬＣ患者中,携带ＧＳＴＰ１Ａ／Ａ基因４９例,Ｇ／Ａ基因３４例,Ｇ／Ｇ基因１１例;携带ＸＲＣＣ１Ｇ／Ｇ基因５２例,Ｇ／Ａ基因３５例,Ａ／Ａ基因７例,均符合Ｈａｒｄｙ Ｗｅｉｎｂｅｒｇ遗传平衡规律。携带ＧＳＴＰ１Ｇ／Ａ＋Ｇ／Ｇ基因型的有效率为４４.４４％,显著高于Ａ／Ａ基因型的２０.４１％（Ｐ＜０.０５）;携带ＸＲＣＣ１Ｇ／Ｇ基因型与Ｇ／Ａ＋Ａ／Ａ基因型的有效率差异无统计学意义（Ｐ＞０.０５）;两基因多态性的联合分析显示,同时携带ＧＳＴＰ１Ｇ／Ａ＋Ｇ／Ｇ和ＸＲＣＣ１Ｇ／Ａ＋Ａ／Ａ基因型的有效率最高,为６６.６７％,但未见统计学意义（Ｐ＞０.０５）。９４例患者中有５例失访,８９例患者的中位ＴＴＰ为６.５个月,携带ＧＳＴＰ１Ｇ／Ａ＋Ｇ／Ｇ基因型的中位ＴＴＰ为８.０个月,Ａ／Ａ基因型为６.０个月,两者差异有统计学意义（Ｐ＜０.０１）;携带ＸＲＣＣ１Ｇ／Ｇ基因型的中位ＴＴＰ为７.０个月,Ｇ／Ａ＋Ａ／Ａ基因型为６.５个月,两者差异无统计学意义（Ｐ＞０.０５）;联合分析显示同时携带ＧＳＴＰ１Ｇ／Ａ＋Ｇ／Ｇ和ＸＲＣＣ１Ｇ／Ａ＋Ａ／Ａ基因型的中位ＴＴＰ最长,为９.５个月,各组间差异有统计学意义（Ｐ＜０.０１）。结论　ＧＳＴＰ１基因多态性与晚期ＮＳＣＬＣ患者接受铂类为主化疗方案的疗效及预后有关,同时携带ＧＳＴＰ１Ｇ／Ａ＋Ｇ／Ｇ和ＸＲＣＣ１Ｇ／Ａ＋Ａ／Ａ基因型患者的化疗有效率高,预后好,但因样本量较小,需要扩大样本进一步验证。     

A multivariate analysis of genomic polymorphisms: prediction of clinical outcome to 5-FU/oxaliplatin combination chemotherapy in refractory colorectal cancer

In this marker evaluation study, we tested whether distinct patterns of functional genomic polymorphisms in genes involved in drug metabolic pathways and DNA repair that predict clinical outcome to 5-fluorouracil (5-FU)/oxaliplatin chemotherapy in patients with advanced colorectal cancer could be identified. Functional polymorphisms in DNA-repair genes XPD, ERCC1, XRCC1, XPA, and metabolising genes glutathione S-transferase GSTP1, GSTT1, GSTM1, and thymidylate synthase (TS) were assessed retrospectively in 106 patients with refractory stage IV disease who received 5-FU/oxaliplatin combination chemotherapy, using a polymerase chain reaction-based RFLP technique. Favourable genotypes from polymorphisms in XPD-751, ERCC1-118, GSTP1-105, and TS-3'-untranslated region (3'UTR) that are associated with overall survival were identified. After adjustment for performance status, the relative risks of dying for patients who possessed the unfavourable genotype were: 3.33 for XPD-751 (P=0.037), 3.25 for GSTP1-105 (P=0.072), 2.05 for ERCC1-118 (P=0.037), and 1.65 for TS-3'UTR (P=0.091) when compared to their respective beneficial genomic variants. Combination analysis with all four polymorphisms revealed that patients possessing > or =2 favourable genotypes survived a median of 17.4 months (95% confidence interval (CI): 9.4, 26.5) compared to 5.4 months (95% CI: 4.3, 6.0) in patients with no favourable genotype. Patients who carried one favourable genotype demonstrated intermediate survival of 10.2 months (95% CI: 6.8, 15.3; P<0.001). Polymorphisms in the TS-3'UTR and GSTP1-105 gene were also associated with time to progression. After adjustment for performance status, patients with an unfavourable TS-3'UTR genotype had a relative risk of disease progression of 1.76 (P=0.020) and those with the unfavourable GSTP1-105 genotype showed a relative risk of progression of 2.00 (P=0.018). The genomic polymorphisms XPD-751, ERCC1-118, GSTP1-105, and TS-3'UTR may be useful in predicting overall survival and time to progression of colorectal cancer in patients who receive 5-FU/oxaliplatin chemotherapy. These findings require independent prospective confirmation.     

DNA repair gene polymorphism associated with sensitivity of lung cancer to therapy

This study aimed to investigate association between single-nucleotide polymorphisms (SNPs) of excision repair cross-complementing gene 1 (ERCC1), excision repair cross-complementing gene 2 (ERCC2), and X-ray repair cross-complementing group 1 (XRCC1) with sensitivity of advanced non-small cell lung cancer (NSCLC) patients to platinum-based chemotherapy. A total of 89 NSCLC patients were recruited and treated with two cycles of platinum-based chemotherapy. DNA was extracted from peripheral lymphocytes for detection of SNPs of ERCC1 Asn118Asn, ERCC2 Lys751Gln, and XRCC1 Arg399Gln. The overall response rate of these patients was 29.2%. There was no statistically significant difference of treatment response between the wild genotypes and the variant genotypes for the ERCC1 Asn118Asn and ERCC2 Lys751Gln gene. The distributions of genotypes XRCC1 Arg399Gln differed significantly between the response and non-response groups (76.9 vs. 23.1%, P = 0.001). The XRCC1 399Arg/Arg genotype carriers had a higher response rate than that of the Gln genotype carriers (OR = 4.81, 95%CI = 1.778-13.013, P = 0.002). The combination of the favorable genotypes of ERCC1, ERCC2, and XRCC1 had a higher response rate compared to that of patients with other genotypes. The combined polymorphisms of ERCC1, ERCC2, and XRCC1 may be associated with sensitivity of NSCLC to platinum-based chemotherapy. Further studies will verify these SNPs as biomarkers for prediction of platinum-based chemotherapy responses of NSCLC patients.     

GSTP1, ERCC1 and ERCC2 Polymorphisms,Expression and Clinical Outcome of Oxaliplatin-based Adjuvant Chemotherapy in Colorectal Cancer in Chinese Population

Aim: Platinum agents have shown to be effective in the treatment of colorectal cancer. We assessed whethersingle nucleotide polymorphisms (SNPs) in GSTP1, ERCC1 Asn118Asn and ERCC2 Lys751Gln might predictthe overall survival in patients receiving oxaliplatin-based chemotherapy in a Chinese population. Methods:SNPs of GSTP1, ERCC1 Asn118Asn and ERCC2 Lys751Gln in 335 colorectal cancer patients were assessedusing TaqMan nuclease assays. Results: At the time of final analysis on Nov. 2011, the median follow-up periodwas 37.7 months (range from 1 to 60 months). A total of 229 patients died during follow-up. Our study showedGSTP1 Val/Val (HR=0.44, 95% CI=0.18-0.98), ERCC1 C/C (HR=0.20, 95% CI=0.10-0.79) and ERCC2 G/G(HR=0.48, 95% CI=0.19-0.97) to be significantly associated with better survival of colorectal cancer. GSTP1Val/Val, ERCC1 C/C and ERCC2 G/G were also related to longer survival among patients with colon cancer,with HRs (95% CIs) of 0.41 (0.16-0.91), 0.16 (0.09-0.74) and 0.34 (0.16-0.91), respectively. Conclusion: GSTP1,GSTP1, ERCC1 Asn118Asn and ERCC2 Lys751Gln genotyping might facilitate tailored oxaliplatin-basedchemotherapy for colorectal cancer patients.     

Prognostic value of expression of ERCC1, thymidylate synthase, and glutathione S-transferase P1 for 5-fluorouracil/oxaliplatin chemotherapy in advanced gastric cancer.

BACKGROUND: The aim of this study was to determine whether expressions of the excision repair cross-complementing (ERCC1), thymidylate synthase (TS), and glutathione S-transferase P1 (GSTP1) predict clinical outcome in patients with advanced gastric cancer treated with fluorouracil (5-fluorouracil)/oxaliplatin chemotherapy. PATIENTS AND METHODS: The study population consisted of 64 advanced gastric cancer patients (median age 51 years). Patients were treated with oxaliplatin 85 mg/m(2) as a 2-h infusion at day 1 plus leucovorin 20 mg/m(2) over 10 min, followed by 5-FU bolus 400 mg/m(2) and 22-h continuous infusion of 600 mg/m(2) at days 1-2. Treatment was repeated in 2-week intervals. The expressions of ERCC1, TS, and GSTP1 of primary tumors were examined by immunohistochemistry. RESULTS: The positive rates of ERCC1, TS, and GSTP1 were 70.3%, 29.7%, and 50.0%, respectively. The patients without ERCC1 expression were more likely to respond to chemotherapy (P = 0.045). There were no significant differences between response and TS or GSTP1 expression pattern (P = 0.813, P = 0.305, respectively). Median overall survival (OS) was significantly longer in patients without ERCC1 expression (P = 0.0396). TS or GSTP1 expression were not related to survival (P = 0.4578, P = 0.8121, respectively). Multivariate analysis revealed that ERCC1 expression significantly impacted on OS (hazard ratio 1.92, P = 0.037). CONCLUSION: Immunohistochemical studies for ERCC1 may be useful in prediction of the clinical outcome in advanced gastric cancer patients treated with 5-FU and oxaliplatin.     

晚期胃癌患者外周血ＥＲＣＣ１基因多态性与奥沙利铂疗效相关性的研究

目的：探讨切除修复交叉互补基因１（ＥＲＣＣ１）Ａｓｎ１１８Ａｓｎ（Ｃ→Ｔ,ｒｓ１１６１５）多态性与中国汉族晚期胃癌患者对奥沙利铂一线化疗效果的关系。方法：７１例晚期胃癌患者化疗前抽静脉血提取ＤＮＡ,以ｒｅａｌ-ｔｉｍｅＰＣＲ法对ＥＲＣＣ１基因进行ＳＮＰ分型。患者接受奥沙利铂化疗,观察疾病控制率（ＣＲ＋ＰＲ＋ＳＤ）及至肿瘤进展时间（ＴＴＰ）,并比较不同基因型与疗效的关系。结果：４７例Ⅳ期胃癌患者可以评价化疗疗效,疾病控制率为５５.３％,Ｃ／Ｃ与Ｃ／Ｔ＋Ｔ／Ｔ基因型在疾病控制组和无效组之间分布无统计学意义（χ２＝2.７５５,Ｐ＝０.０９７）。７１例晚期胃癌患者中位ＴＴＰ为６个月,Ｃ／Ｔ＋Ｔ／Ｔ基因型患者其中位ＴＴＰ为５个月,与纯合基因型Ｃ／Ｃ中位ＴＴＰ６个月相比,差异无统计学意义（ＯＲ＝０.６１５,Ｐ＝０.０７１）。其中２４例Ⅲ期胃癌患者中位ＴＴＰ为８个月,Ｃ／Ｔ＋Ｔ／Ｔ型患者中位ＴＴＰ为７个月,与纯合基因型Ｃ／Ｃ中位ＴＴＰ８个月相比,差异无统计学意义（ＯＲ＝０.３９７,Ｐ＝０.１１１）。结论：ＥＲＣＣ１Ａｓｎ１１８Ａｓｎ基因多态性与中国汉族晚期胃癌患者接受奥沙利铂一线化疗后的临床效果有相关趋势,需要进一步观察论证。     

ERCC1, XRCC1, and GSTP1 Polymorphisms and Treatment Outcomes of Advanced Epithelial Ovarian Cancer Patients Treated with Platinum-based Chemotherapy

Objective: The first line regimen for treating epithelial ovarian cancer (EOC) is platinum-based chemotherapy. Various factors impact its effectiveness including polymorphisms of enzymes in platinum-related metabolism processes.  Methods: We conducted the study to investigate the association between polymorphisms of ERCC1, XRCC1 and GSTP1, which responsible for platinum’s metabolisms in Thai epithelial ovarian cancer patients. Results: Fifty-two patients with advanced epithelial ovarian cancer were enrolled into this study. Genotyping analysis of ERCC1 (C->A, rs3212986), XRCC1 (A->G, rs25487) and GSTP (A->G, rs1695) were performed which variant allele frequencies were found at 35.6%, 28.9% and 10.6%, respectively. Patients with homozygous variant type (A/A) of ERCC1 C8092A had higher rate of platinum-resistance (75% vs 16.7%, p =0.046). In addition, the significant association of GSTP1 polymorphism and grade 2 anemia was found. Patients with A/G genotype of GSTP1 had higher rate of grade 2 anemia (81.8% vs 46.3%, p =0.036). Conclusions: Genetic polymorphisms of ERCC1, and GSTP1 might be useful biomarkers for prediction of clinical benefit and toxicities of platinum-based chemotherapy in Thai epithelial ovarian cancer patients.