中国人群非小细胞肺癌发生发展的全基因组关联分析

Our research funded by the National Nature Science Funds of China (Grant No. 30901233) completed the genotyping of tagging SNPs in 15q25 with a design of molecular epidemiology and identified some SNPs associated with lung cancer risk. We also attended the first genome-wide association study of lung cancer in China and did a more in-depth discussion for other genetic variants in 15q25 and lung cancer. Furthermore, we examined the associations between SNPs involved in several biological pathways and the development of lung cancer. Until now, we have published 3 papers and submitted one, which were all fund by the National Nature Science Funds of China (Grant No. 30901233). To extend the research on the development of lung cancer, we will conducted a genome-wide analysis for the development of non-small cell lung cancer in Chinese population on the basis of preliminary research progress and clinical/following-up information of patients. The aim of the study is to find the special biomarkers for non-small cell lung cancer (NSCLC) in China, discuss the difference of biomarkers in patients with different characteristics and determine the biological function of SNPs in the development of NSCLC.

在青年科学基金项目资助下（批准号：30901233），采用大样本的分子流行病学研究设计检测了15q25区段多个标签SNPs的基因型，建立了相应的与肺癌发生发展相关的基因SNPs 谱及预测模型；在此基础上，密切关注国内外全基因组关联研究（GWAS）的进展，参与了中国首个肺癌GWAS，并应用相关数据对于15q25区域的遗传变异与中国人群肺癌的关联进行了更深入的探讨；此外，探讨了多个通路的基因SNPs与肺癌发生发展的关系，发现了多个SNPs可影响非小细胞肺癌患者的预后。已发表基金标注的SCI论文3篇，投稿1篇。后续项目拟在前期研究成果的基础上，结合首个中国人群的肺癌GWAS数据及临床治疗/预后信息收集，进行中国人群非小细胞肺癌发生发展的全基因组关联分析，以期发现中国人群非小细胞肺癌发生发展的特定标志物，并进行相关SNPs的功能研究，阐述其影响肺癌发生发展的生物学机制。

本研究系统整合全基因组遗传变异、临床预后和化疗毒副反应等数据，围绕遗传变异与中国人群非小细胞肺癌（NSCLC）发生发展以及治疗预后的关联及相应的生物学机制等开展了系列研究，创新性地发现了一批与非小细胞肺癌发生发展相关的遗传位点，鉴定了晚期肺癌患者临床预后以及化疗毒副反应相关的多个遗传变异，并通过功能学实验阐明了多个遗传变异可通过影响相关位点的甲基化水平、调控基因/miRNA表达而影响肺癌患者的预后。上述研究结果已发表基金标注SCI论文12篇，累计影响因子（IF）为59.7，其中IF>5的6篇。本研究发现了与我国人群肺癌临床预后相关的生物标志物，可将其用于患者的预后预测，对今后肺癌的个体化治疗及预后改善等均具有重要的现实意义。