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。     

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     

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.     

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。     

基因多态性与FOLFOX方案治疗胃肠癌敏感性的关系

目的研究MTHFR C677T和XRCC1 G28152A基因多态性与接受FOLFOX方案的胃肠癌患者化疗敏感性与毒副反应的关系。方法经FOLFOX方案化疗的进展期胃肠癌48例（22例有临床可观察肿瘤病灶）,化疗前抽外周静脉血2 mL,用PCR-RFLP技术检测研究对象的MTHFR C677T和XRCC1 G28152A基因型。化疗两周期后全面评价疗效及毒副反应,并随访观察进展情况。结果 （1）48例胃肠癌患者,MTHFR 677 C/C、C/T、T/T基因型分别为39.6%、37.5%及22.9%。XRCC1 28152 G/G、G/A、A/A基因型分别为52.1%、45.8%及2.1%。22例可观察肿瘤病灶者MTHFR 677 C/C、C/T、T/T基因型疾病控制率分别为14.2%、66.6%和100.0%,T/T基因型明显高于C/C型（P〈0.05）;XRCC1 28152 G/G、G/A＋A/A基因型疾病控制率分别为90.9%、36.4%,差异有统计学意义（P〈0.05）。（2）48例患者带有MTHFR677 C/C、C/T、T/T基因型的2年无复发生存率分别为21.1%、36.8%和72.7%,T/T基因型明显高于C/C型（P〈0.05）;XRCC1 28152 G/G、G/A＋A/A基因型2年无复发生存率分别为52.0%和21.7%,差异有统计学意义（P〈0.05）。（3）患者接受FOLFOX方案化疗后带有MTHFR 677 C/T、T/T患者恶心/呕吐的发生率（77.8%、81.8%）明显高于C/C基因型患者（26.3%）。XRCC1 28152 G/G、G/A＋A/A基因型恶心/呕吐分别为44.0%,78.3%,差异有统计学意义（P〈0.05）,其余毒副反应与基因型之间差异均无统计学意义（P〉0.05）。结论 MTHFR C677T和XRCC1 G28152A基因多态对胃肠癌接受FOLFOX方案化疗疗效与毒性有良好的提示作用。     

切除修复交叉互补基因1和X线修复交叉互补基因1及谷胱甘肽巯基转移酶π 1多态性与晚期胃癌患者生存期的关系

目的 探讨切除修复交叉互补基因1(ERCC1)、X线修复交叉互补基因1(XRCC1)和谷胱甘肽巯基转移酶π1(GSTP1)多态性与中国晚期胃癌患者接受含奥沙利铂方案一线化疗后生存期的关系.方法 85例晚期胃癌患者接受奥沙利铂+5-氟尿嘧啶为基础的联合化疗方案化疗,并在化疗前抽取患者静脉血,提取基因组DNA,以实时荧光定量PCR法行多态性检测,比较不同基因型与患者生存期的关系.结果 85例患者中位至疾病进展时间为5.3个月,中位生存期为8.0个月.ERCC1-118 C/C、XRCC1-399 G/G和GSTP1-105 A/G+G/G基因型为优势基因型,携带3个、2个、1个、0个优势基因型患者的中位生存期分别为12.5、10.0,6.5和4.5个月,组间差异有统计学意义(χ2=35.54,P<0.01).结论 ERCC1-118、XRCC1-399和GSTP1-105基因多态性与中国晚期胃癌患者接受含奥沙利铂化疗方案一线化疗后的生存期相关,可预测患者的预后.     

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。     

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/C 50.51%、C/T 41.41%、T/T8.08%;XRCC1 Arg399Gln基因突变频率为:G/G 52.53%、G/A 38.38%、A/A 9.09%.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ERCC1 C/C和XRCC1 G/G基因型、ERCC1 C/C和XRCC1 G/A A/A基因型、ERCC1 C/T T/T和XRCC1 G/G基因型、以及ERCC1 C/T T/T和XRCC1 G/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.     

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.     

Genetic Polymorphism of XRCC1 Correlated with Response to Oxaliplatin-Based Chemotherapy in Advanced Colorectal Cancer

To examine the association between genetic polymorphisms of XRCC1 Arg399Gln(G→A) and response to oxaliplatin-based chemotherapy in advanced colorectal cancer. XRCC1 genotypes of totally 99 patients(37 stage III, 62 stage IV)with advanced colorectal cancer treated with oxaliplatin-based chemotherapy were detected by TaqMan-MGB probe allelic discrimination method. And clinical response of 62 patients in stage IVafter 2 to 3 cycles of chemotherapy were evaluated. Also time to progress (TTP) of all patients were evaluated. Of the genotype frequencies in all patients, up to 52.53?% were G/G genotype, 9.09?% were A/A genotype, and 38.38?% were G/A genotype. The response rate (CR+PR) of 62 patients in stage IV was 61.29?% (19/31). Patients with G/G genotype showed enhanced respond to chemotherapy compared to those with G/A+A/A (x (2)?=?5.6, P?=?0.029; OR?=?3.845, 95?%CI?=?1.231?~?12.01, P?=?0.018). Individuals with the G/G genotype had a TTP of 10.0 (8.88-11.12) months, those with the G/A+A/A genotype had an TTP of 5.0(4.26-5.74) months. The log-rank test was marginally significant (x (2)?=?29.20, P?相似文献   

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。     

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。     

晚期食管癌患者血清XRCC1基因多态性与铂类化疗疗效相关性的研究

目的:探讨XRCC1Arg399Gln(G+A)基因多态性与晚期食管癌对以奥沙利铂为主的化疗敏感性的关系。方法:晚期食管癌患者87例(Ⅲ期41例,Ⅳ期46例),采用改良FOLFOX方案化疗,46例Ⅳ期患者3个周期后进行临床疗效评价,87例患者统计至疾病进展时间(TTP)。应用TaqMan-MGB探针等位基因分型技术进行基因分型。结果:54.2%为A/A,34.5%为A/G,11.5%为G/G。Ⅳ期46例患者化疗后临床获益率(CR+PR+SD)为52.17%,A/A、G/A+G/G在化疗敏感组与不敏感组中的分布具有统计学意义(χ2=6.213,P=0.023)。87例患者中位TTP 8个月,A/A基因型11个月,G/A+G/G基因型4个月,两者比较差异有统计学意义(χ2=27.781,P<0.01)。结论:XRCCl Arg399Gln基因多态性与晚期食管癌患者对奥沙利铂化疗的敏感性与生存时间相关。     

The combination of ERCC1 and XRCC1 gene polymorphisms better predicts clinical outcome to oxaliplatin-based chemotherapy in metastatic colorectal cancer

Purpose

To evaluate the effect of excision repair cross-complementing group 1 (ERCC1) and X-ray cross-complementing group 1 (XRCC1) gene polymorphisms on treatment outcome in patients receiving oxaliplatin-based regimens for metastatic colorectal cancer.

Methods

Hundred and thirteen patients with a diagnosis of metastatic colorectal cancer were treated with oxaliplatin-based chemotherapy. ERCC1 codon 118C/T and XRCC1 codon 399A/G polymorphisms were tested by real-time polymerase chain reaction (RT-PCR) method in peripheral blood lymphocytes of these patients. Disease control rates and survivals were compared by types of genotypes.

Results

Analyses of the patterns of the polymorphism located at ERCC1 codon 118 showed that 55 (48.67%) patients were homozygous for C/C genotype, 15 (13.27%) were homozygous for the T/T genotype, and 43 (38.06%) were heterozygous for C/T genotype. Analyses of the polymorphism located at XRCC1 codon 399 showed that 61 (53.98%) patients were homozygous for A/A genotype, 13 (11.50%) were homozygous for the G/G genotype, and 39 (34.52%) were heterozygous for A/G genotype. After two cycles of chemotherapy, there was complete response (CR) in 1 patient, partial response (PR) in 24 patients, and stable disease (SD) in 56 patients. Altogether in 81 (71.68%) patients the disease was controlled after chemotherapy. Thirty-two (28.32%) patients showed disease progression. After adjusting for some clinical factors, both the ERCC1 polymorphism and the XRCC1 polymorphism lost their roles in predicting DCR (P = 0.662, P = 0.631) and MST (P = 0.692, P = 0.572). But the combination of ERCC1 and XRCC1 polymorphisms was significantly associated with DCR (P = 0.01) and MST (P = 0.000) independently.

Conclusions

This is the first study which showed that polymorphisms of ERCC1 and XRCC1, in combination not individually, were independent predictors for DCR and OS. This may contribute to the selection of patients who would benefit from oxaliplatin-based chemotherapy for metastatic colorectal cancer.     

Prospective assessment of XPD Lys751Gln and XRCC1 Arg399Gln single nucleotide polymorphisms in lung cancer.

PURPOSE: XRCC1 and XPD play key roles in the repair of DNA lesions and adducts. Contrasting findings have been reported on the effect of polymorphisms of these genes on the response to platinum-based chemotherapy in advanced non-small-cell lung cancer (NSCLC). This study aimed to investigate the relationship between the XPD Lys751Gln and XRCC1 Arg399Gln genotypes and outcome in lung cancer patients. EXPERIMENTAL DESIGN: We genotyped 203 NSCLC and 45 small-cell lung carcinoma (SCLC) patients for the two polymorphisms. Most of the patients (81%) received a platinum-based chemotherapy. RESULTS: The patients' genotype frequencies did not significantly differ from controls and both groups were in Hardy-Weinberg equilibrium for the two polymorphisms. The XRCC1399 Gln/Gln variant genotype was associated with a higher median survival time (80 weeks versus 54.6 weeks for the Arg/Gln heterozygous and 55.6 weeks for the wild-type Arg/Arg genotype; P=0.09). At the multivariable analysis adjusted for histology, stage of the disease, performance status, age, and gender, the Gln/Gln genotype was associated with a better survival of borderline significance in the subgroup of patients treated with cisplatin (hazard ratio, 0.55; 95% CI, 0.30-1.00); this association became significant for those with grade 3-4 clinical toxicity (hazard ratio, 0.46; 95% CI, 0.22-0.98). No association between XPD Lys751Gln genotype and clinical outcome was found. CONCLUSION: This prospective investigation provides suggestive evidence of a favorable effect of the XRCC1399 Gln/Gln genotype on survival in platinum-treated NSCLC and, for the first time, in SCLC patients also. This contrasts with other authors who did not include non-platinum-treated patients, but it does fit the expectation for a suboptimal ability to remove DNA adducts.     

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.     

晚期食管癌患者血清XRCC1基因多态性与铂类化疗疗效相关性的研究

目的：探讨XRCC1Arg399Gln（G＋A）基因多态性与晚期食管癌对以奥沙利铂为主的化疗敏感性的关系。方法：晚期食管癌患者87例（Ⅲ期41例,Ⅳ期46例）,采用改良FOLFOX方案化疗,46例Ⅳ期患者3个周期后进行临床疗效评价,87例患者统计至疾病进展时间（TTP）。应用TaqMan-MGB探针等位基因分型技术进行基因分型。结果：54.2%为A/A,34.5%为A/G,11.5%为G/G。Ⅳ期46例患者化疗后临床获益率（CR＋PR＋SD）为52.17%,A/A、G/A＋G/G在化疗敏感组与不敏感组中的分布具有统计学意义（χ2=6.213,P=0.023）。87例患者中位TTP 8个月,A/A基因型11个月,G/A＋G/G基因型4个月,两者比较差异有统计学意义（χ2=27.781,P〈0.01）。结论：XRCCl Arg399Gln基因多态性与晚期食管癌患者对奥沙利铂化疗的敏感性与生存时间相关。