基于全基因组关联研究的荟萃分析识别肺癌易感基因位点  

Genome-wide Meta-analysis identified susceptibility loci for lung cancer

作　　者：黄文杰 郑心怡 王雪梅[2] 张翠珍 邱晓燕 HUANG Wenjie;ZHENG Xinyi;WANG Xuemei;ZHANG Cuizhen;QIU Xiaoyan(Department of Pharmacy,Huashan Hospital,Fudan University,Shanghai 200040,China;Department of Pharmacy,The First Hospital of Jilin University,Changchun 130031,China)

机构地区：[1]复旦大学附属华山医院药剂科,上海200040 [2]吉林大学第一医院药剂科,长春130031

出　　处：《中国临床药学杂志》2024年第6期425-431,共7页Chinese Journal of Clinical Pharmacy

摘　　要：目的寻找更多的肺癌遗传易感位点,筛选肺癌潜在治疗靶点。方法收集4项全基因组关联研究(涵盖日本、韩国、芬兰和英国人群)的数据,通过R软件(版本4.1.0)进行质量控制后使用METAL软件(Windows平台)分别对东亚人群、欧洲人群和跨种族人群进行逆方差加权荟萃分析,以识别全基因组显著性位点(P<5.0×10^(-8))。使用RegulomeDB、3DSNP和HaploReg数据库对全基因组显著性位点进行功能注释。采用基于基因的分析方法,识别那些达到显著差异的肺癌风险基因(P<2.57×10^(-6))。结果通过荟萃分析,共发现4个位点(3q28、6p21.32、22q12.1和20q13.33),33个与肺癌风险显著相关的新的单核苷酸多态性,同时发现2个与肺癌风险相关的尚未被报道过的基因(TTC28和CCDC117,均在22q12.1位点上)。结论该研究成功鉴定了与肺癌风险相关的新的遗传变异和基因,为理解肺癌的遗传机制提供了新的视角。AIM To search for additional genetic susceptibility loci for lung cancer,screening potential therapeutic sites.METHODS Summary data from 4 preceding genome-wide association studies conducted in Japan,South Korea,Finland,and the United Kingdom were systematically compiled.Then,quality control procedures were executed utilizing the R software environment(Version 4.1.0).Subsequently,METAL software(Windows)was used to conduct inverse-variance weighted Meta-analysis on the data from East Asian,European,and trans-ethnic populations to identify genome-wide significant loci(P<5.0×10^(-8)).Subsequent functional annotations for the identified genome-wide significant loci were conducted using the RegulomeDB,3D-SNP,and HaploReg databases.Lung cancer risk genes reaching significant differentiation(P<2.57×10^(-6))were discerned by using a gene-based analytical approach.RESULTS A total of 33 novel SNPs were identified at 4 loci(3q28,6p21.32,22q12.1,and 20q13.33),which were found to be significantly associated with lung cancer risk.Additionally,2 new genes,TTC28 and CCDC117 located at 22q12.1,were discovered to be linked with lung cancer susceptibility.CONCLUSION This investigation has successfully identified new genetic variants and genes associated with the risk of lung cancer,providing a new perspective on the genetic mechanisms of lung cancer.

关 键 词：肺癌 基因组关联研究 单核苷酸多态性 易感基因位点 

分 类 号：R734.2[医药卫生—肿瘤]