铂类药物的主要代谢途径基因Regulome-SNP与NSCLC疗效和生存率相关研究

Some patients’ conditions have been improved after chemotherapy of NSCLC's, but did not benefit from curative effect and prognosis is still disputed. Platinum is one of chemotherapy drugs for NSCLC. The process in vivo was affected by DNA damage and repair, drug metabolism and detoxification, cell cycle and apoptosis, drug transporters and membrane receptor, and also affected by the cumulative effects of environmental factors. In this study, we will screen 117 functional SNPs from 28 genes by using HapMap-SNP, NCBI-SNP DB, Regulome-DB. The relationship between SNP frequency and curative effect of chemotherapy on NSCLC will be observed. The functional study will be performed to prove the effect of SNP. The Regulome target gene location will be determined by 3C technology. We will study the specific Regulome-SNP sites, NSCLC assessment after chemotherapy and 2 year DFS. These results will provide scientific basis for improving the lifestyle and eating habits to take early preventive measures.

NSCLC化疗后部分患者的病情得到了一定的改善，但对未受益患者的疗效和预后情况仍存在争议。铂类药物是NSCLC的重要化疗药物之一，其体内过程受DNA的损伤与修复、药物代谢与解毒、细胞周期与凋亡、药物转运体与膜受体等代谢途径基因影响的同时也受累积不良环境因素的影响。本课题利用HapMap-SNP和NCBI-SNP数据库以及Regulome-DB新技术，在铂类药物主要代谢途径相关的28个基因中筛选出117个功能性SNP。本研究观察上述SNP基因分布频率与环境因素对NSCLC化疗后疗效和2年无病生存率的交互作用，并通过功能实验鉴定SNP对靶标的影响，探讨不同基因型SNP对靶标的调控作用，利用3C技术确定Regulome与靶基因作用位置。本研究结果将为确定NSCLC的特异性Regulome-SNP位点、评估化疗后疗效及2年无病生存率、通过改善生活方式和饮食习惯采取早期预防措施提供科学依据。