ERCC5基因启动子区单核苷酸位点多态性与晚期大肠癌奥沙利铂化疗敏感性的关系  

Relationship between ERCC5 promoter polymorphism and chemosensitivity of oxaliplatin-based chemotherapy in patients with advanced colorectal cancer

作　　者：陈建芳[1] 梁后杰[1] 王东[1] 童晶涛[1] 廖玲[2] 

机构地区：[1]第三军医大学西南医院肿瘤中心,重庆400038 [2]第三军医大学大坪医院野战外科研究所肿瘤中心,400042

出　　处：《临床肿瘤学杂志》2009年第10期870-874,共5页Chinese Clinical Oncology

摘　　要：目的:研究切除修复交叉互补基因5(ERCC5)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化疗敏感性的关系。方法:收集83例晚期大肠癌患者以奥沙利铂为主的化疗开始前的静脉血,提取基因组DNA,应用PCR-LDR方法检测ERCC5基因启动子区3个SNP位点-1415C>T(rs2094258)、-763A>G(rs2016073)及-413C>T(rs943245)的多态性,分析不同基因型与化疗敏感性的关系。结果:本研究人群中各多态性位点基因型分布均符合Hardy-Weinberg平衡,但在-413C>T位点,只观察到了CC基因型,未发现遗传多态。携带-763GG基因型的患者化疗有效率高于携带-763AA基因型患者(χ2=8.568,P=0.008)及-763AG基因型患者(χ2=4.475,P=0.046)。携带-763A等位基因的患者化疗失败风险是携带-763G等位基因患者的2.39倍(OR=2.390,95%CI:1.241～4.601;P=0.009)。-1415C>T多态性与化疗敏感性之间无显著相关性。结论:中国汉族晚期大肠癌患者ERCC5启动子区-763A>G多态性与奥沙利铂化疗敏感性相关。Objective：To study the relationship between single nucleotide polymorphisms（SNPs） in the promoter of ERCC5 （ excision repair cross complementation group 5） gene and ehemosensitivity of oxaliplatin-based chenlotherapy in Chinese patients with advanced colorectal cancer. Methods：DNA was extracted from peripheral blood cells before oxaliplatin-based chemotherapy in 83 advanced eolorectal cancer patients. Three polymorphisms in the ERCC5 gene promoter , -1415 C 〉 T （ rs2094258 ） ,-763A 〉 G （rs2016073） and -413C 〉 T（ rs943245 ） were detected by PCR-LDR（ polymerase chain reaction-ligation detection reaction）. Statistical analysis was conducted to investigate the association between polymorphism and ehemosensitivity. Results：The genotype distribution for each polymorphism was found to be in Hardy-Weinberg equilibrium in the study population. Only CC genotype was ohserved at site -413C 〉 T and no genetic variation was observed. The response rate among patients with -763GG genotypes（72.7% ） was significantly higher than that with other genotypes（22. 2% for -763AA genotype, X2 = 8. 568, P = 0. 008 and 37.2%） for -763AG genotype, .g2 = 4. 475,P = 0. 046）. Individuals with -763A allele had higher risk of non-response comparing to those carrying -763G allele （OR 2. 390, 95% CI ： 1. 241-4. 601, P = 0. 009）. No significant association or trend was found between -1415C 〉 T polymorphism and chemosensitivity. Conclusion：The results suggested that ERCC5-763A 〉 G polymorphism may be associated with chemosensitivity of oxali- platin-based chemotherapy in Chinese patients with advanced coloreetal cancer.

关 键 词：切除修复交叉互补基因5 多态性 大肠癌 奥沙利铂 化疗敏感性 

分 类 号：R735.3[医药卫生—肿瘤]