Comprehensive functional annotation of susceptibility variants identifies genetic heterogeneity between lung adenocarcinoma and squamous cell carcinoma
作者机构：Department of EpidemiologyCenter for Global HealthSchool of Public HealthNanjing Medical UniversityNanjing 211166China State Key Laboratory of Reproductive MedicineCenter for Global HealthNanjing Medical UniversityNanjing 211166China Department of BioinformaticsSchool of Biomedical Engineering and InformaticsNanjing Medical UniversityNanjing 211166China Jiangsu Key Lab of Cancer BiomarkersPrevention and TreatmentCollaborative Innovation Center for Cancer MedicineNanjing Medical UniversityNanjing 211166China China International Cooperation Center for Environment and Human HealthSchool of Public HealthNanjing Medical UniversityNanjing 211166China Division of Cancer Epidemiology and GeneticsNational Cancer InstituteBethesdaMD 20892-9304USA Department of Integrative OncologyBritish Columbia Cancer AgencyVancouverBC V5Z 1L3Canada Faculty of MedicineUniversity of Oviedo and CIBERESPOviedo 33006Spain Program in EpidemiologyPublic Health Sciences DivisionFred Hutchinson Cancer Research CenterSeattleWA 98109-1024USA Public Health Sciences DivisionSwedish Cancer InstituteSeattleWA 98026USA Department of Clinical BiochemistryCopenhagen University HospitalCopenhagen DK-1017Denmark National Cancer InstituteBethesdaMD 20892-9304USA Genetic Epidemiology GroupInternational Agency for Research on CancerLyon 69372France Cancer Center Cluster Salzburg at PLUSDepartment of Molecular BiologyUniversity of SalzburgHeidelberg 5020Austria Institute of Medical InformaticsBiometry and EpidemiologyChair of EpidemiologyLudwig Maximilians UniversityMunichBavaria 80539Germany Department of Genetic EpidemiologyUniversity Medical Center GoettingenGoettingen 37075Germany Technion Faculty of MedicineCarmel Medical CenterHaifa 3448516Israel Markey Cancer CenterUniversity of KentuckyLexingtonKY 40506-0054USA Department of Molecular and Clinical Cancer MedicineRoy Castle Lung Cancer Research ProgrammeThe University of Liverpool Institute of Translational MedicineLiverpool L697ZXUK Department of EpidemiologyThe University of TexasMD Anderson Cancer CenterHoustonTX 77079USA Department of EpidemiologyUniversity of Hawaii Cancer CenterHonoluluHI 96813USA Department of Clinical SciencesLund UniversityBMC F1222184Sweden Epidemiology DivisionPrincess Margaret Cancer CenterTorontoON M4Y 2H8Canada Epidemiology DivisionLunenfeld-Tanenbuaum Research InstituteSinai Health SystemTorontoON M5G 1X5Canada Department of NeurologyDartmouth-Hitchcock Medical CenterLebanonNH 03756USA Department of Health EvidenceRadboud University Medical CenterNijmegen 91016500 HBGermany National Institute of Occupational Health(STAMI)Oslo Pb 5330Norway Department of Medical BiosciencesUmeåUniversityUmea 90187Sweden Department of Radiation SciencesUmeåUniversityUmea 90187Sweden Division of Cancer Epidemiology and GeneticsNational Cancer InstituteRockvilleMD 20850USA Academic Unit of Clinical OncologyUniversity of SheffieldSheffield S102TNUK College of PharmacyWashington State UniversitySpokaneWA 99210USA Department of Cancer EpidemiologyH.Lee Moffitt Cancer Center and Research InstituteTampaFL 12902USA Department of Thoracic SurgeryDivision of EpidemiologyVanderbilt University Medical CenterNashvilleTN 37232USA Department of Epidemiology Research ProgramAmerican Cancer SocietyAtlantaGA 30303USA Department of Environmental HealthHarvard School of Public HealthDepartment of MedicineHarvard Medical School/Massachusetts General HospitalBostonMA 02115USA Baylor College of MedicineInstitute for Clinical and Translational ResearchHoustonTX 21202USA
出 版 物：《Frontiers of Medicine》 (医学前沿（英文版）)
年 卷 期：2021年第15卷第2期
页 面：275-291页
核心收录：
学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学]
基 金：the Key International(Regional)Cooperative Research Project(No.81820108028) the National Natural Science Foundation of China(Nos.81521004,81922061,81973123,and 81803306) the Science Foundation for Distinguished Young Scholars of Jiangsu(No.BK20160046) the Priority Academic Program for the Development of Jiangsu Higher Education Institutions(Public Health and Preventive Medicine) the National Cancer Institute,National Institutes of Health of USA through grants U01-CA063673,UM1-CA167462,and U01-CA167462
主 题：lung cancer genome-wide association study function annotation immune homologous recombination repair deficiency genetic heterogeneity
摘 要：Although genome-wide association studies have identified more than eighty genetic variants associated with non-small cell lung cancer(NSCLC)risk,biological mechanisms of these variants remain largely *** integrating a large-scale genotype data of 15581 lung adenocarcinoma(AD)cases,8350 squamous cell carcinoma(SqCC)cases,and 27355 controls,as well as multiple transcriptome and epigenomic databases,we conducted histology-specific meta-analyses and functional annotations of both reported and novel susceptibility *** identified 3064 credible risk variants for NSCLC,which were overrepresented in enhancer-like and promoter-like histone modification peaks as well as DNase I hypersensitive *** factor enrichment analysis revealed that USF1 was AD-specific while CREB1 was *** annotation and genebased analysis implicated 894 target genes,including 274 specifics for AD and 123 for SqCC,which were overrepresented in somatic driver genes(ER=1.95,P=0.005).Pathway enrichment analysis and Gene-Set Enrichment Analysis revealed that AD genes were primarily involved in immune-related pathways,while SqCC genes were homologous recombination deficiency *** results illustrate the molecular basis of both wellstudied and new susceptibility loci of NSCLC,providing not only novel insights into the genetic heterogeneity between AD and SqCC but also a set of plausible gene targets for post-GWAS functional experiments.
维普期刊数据库
同方期刊数据库