泛素蛋白酶体通路基因SNPs与晚期食管鳞癌紫杉醇敏感性

项目名称： 泛素蛋白酶体通路基因SNPs与晚期食管鳞癌紫杉醇敏感性

项目编号： No.81201954

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 肿瘤学2

项目作者： 刘莺

作者单位： 郑州大学

项目金额： 23万元

中文摘要： 食管癌发病率在我国恶性肿瘤中已上升为第四位，其中食管鳞癌所占比例达90%以上。紫杉醇是晚期食管鳞癌化疗的基础药物，但不同患者的临床疗效和毒副反应相差甚远，提示个体遗传因素在药物敏感性中意义重大。单核苷酸多态性（SNPs）是药物敏感性差异的重要遗传学基础,相关基因特异SNPs不仅影响治疗结果，而且可以作为疗效和毒副反应的预测因子。本课题拟通过泛素-蛋白酶体（ubiquitin-proteasome）通路FBW7和MCL1等基因SNPs研究策略对紫杉醇化疗的疗效和毒性作用进行临床研究，并探讨影响总生存期的基因型和临床特征，以期发现中国人群特有的能够预测紫杉醇疗效和毒副作用的SNPs位点，为晚期食管鳞癌化疗个体化方案的选择、实施提供依据。

中文关键词： 泛素蛋白酶体通路；单核苷酸多态性；紫杉醇；食管鳞状细胞癌；化疗

英文摘要： The incidence of esophageal cancer has risen to 4th in malignant tumor in China, and more than 90% patients are squamous cell carcinoma. Taxol is the foundation of chemotherapy drug for advanced esophageal squamous cell carcinoma. However, the clinical effect and adverse reaction are entirely different among different patients, which indicate that individual genetic factors is very significant for drug sensitivity. Singal nucleotide polymorphisms (SNPs) is the critical genetic basis for the difference of drug sensitivity. Gene specific SNPs genotype not only influenced the prognosis of the treatment, and could be used as a clinical effect and the toxicity of the predictors. This topic is to study the pharmacogenomics of taxol and to observe the relations of genotype and clinical characteristics which will be able to affect the overall survival through the ubiquitin-proteasome-protease body pathways FBW7 and MCL-1 gene SNPs strategies on chemotherapy effects and toxicity. According to the results we expect to find SNPs sites which can predict the efficacy and the toxicity of taxol in special pepole in China, to guide the clinical chemotherapy. The patients with advanced esophageal squamous cell carcinoma would accept resonable treatment during the limited time. At the same time, we can provide the scientific ba

英文关键词： ubiquitin-proteasome pathway；single nucleotide polymorphisms；paclitaxel；esophageal squamous cell carcinoma；chemotherapy