晚期胃癌病人血清XRCC1基因多态性与奥沙利铂化疗效果的相关性_医学论文.docVIP

晚期胃癌病人血清XRCC1基因多态性与奥沙利铂化疗效果的相关性_医学论文 晚期胃癌病人血清XRCC1基因多态性与奥沙利铂化疗效果的相关性_医学论文 作者：姜健 梁军 李青芳 宋珊爱 孙莹莹 【摘要】 目的 探讨XRCC1 Arg399Gln(G→A)基因多态性与晚期胃癌对以奥沙利铂为主的化疗敏感性的关系。方法 晚期胃癌病人94例(Ⅲ期34例，Ⅳ期60例),应用以奥沙利铂为主的方案化疗，对60例Ⅳ期病人化疗2～3个周期后进行临床疗效评价，全部病人统计至疾病进展时间(TTP)。应用TaqMan探针等位基因分型技术进行基因分型。结果 54.26%病人基因型为G/G，8.50％为A/A，37.24％为G/A。Ⅳ期60例病人化疗后临床获益率（CR+PR＋SD）为70%,G/G、G/A+A/A在化疗敏感组（CR+PR＋SD）与不敏感组（PD）中的分布差异有显著性（χ2=6.747,0.05OR=4.680，95%CI=1.397～15.682,P=0.009)。94例病人中位TTP为9.0 个月，G/G基因型为10.5个月，G/A+A/A基因型为7.0个月，两者比较差异有显著性(χ2=7.113,0.01)。结论XRCC1 Arg399Gln基因多态性可能与晚期胃癌病人对奥沙利铂化疗的敏感性及生存时间相关。 【关键词】 胃肿瘤；基因；多态性,限制性片段长度；奥沙利铂；药物疗法；X线修复交叉互补基因1 　　［ABSTRACT］ Objective To study the correlation between genetic polymorphisms of XRCC1 Arg399Gln (G→A) and response to oxaliplatinC). Methods Ninetyfour patients with AGC (34 with stage Ⅲ, and 60 with stage Ⅳ) were treated with oxaliplatinbased chemotherapy. Clinical efficiency in 60 patients with stage Ⅳ was assessed after 2-3 cycles of therapy, all the patients were followed until time to progress (TTP). XRCC1 genotypes were detected by TaqManMGB probe methods. Results 54.26% were G/G genotype, 8.50％ were A/A genotype, and 37.24％were G/A genotype. The clinical benefit rate (CR+PR＋SD) was 70%. Patients with G/G genotype showed distinct preponderance compared to those with G/A+A/A, between response group (CR+PR＋SD) and non.0 months. The significant differences between them were noticed (χ2=7.113,0.01).Conclusion The XRCC1 Arg399Gln genetic polymorphisms may be associated with the clinical response to oxaliplatinbased chemotherapy and survival time in patients with advanced gastric cancer. 　　［KEY WORDS］ stomach neoplasms gene Polymorphism, restriction fragment length oxaliplatin drug therapy X 　　奥沙利铂是第三代铂类抗肿瘤药，为细胞周期非特异性药物,该药以DNA为作用靶点，铂原子与DNA链形成交联，从而阻断其复制和转录。奥沙利铂与氟尿嘧啶临床抗癌有协同作用，以两者为基础的化疗方案是目前晚期胃癌治疗的常用方案之一。X线修复交叉互补基因1 (XRCC1) 是参与碱基切除修复(BER)且与铂类药物抵抗有关的重要因子，该基因第10号外显子上第399位密码子的单核苷酸多态性(SNP)导致氨基酸的替代变化(精氨酸→谷氨酰胺),从而可以改变DNA损伤修复能力,影响个体对铂类药物的敏感性。多项研究结果显示,XRCC1 Arg399Gln多态性与