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Comprehensive functional annotation of susceptibility variants identifies genetic heterogeneity between lung adenocarcinoma and squamous cell carcinoma

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Frontiers of Medicine 2021年第2期15卷 275-291页

作者： Na Qin Yuancheng Li Cheng Wang Meng Zhu Juncheng Dai Tongtong Hong Demetrius Albanes Stephen Lam Adonina Tardon Chu Chen Gary Goodman Stig EBojesen Maria Teresa Landi Mattias Johansson Angela Risch H-Erich Wichmann Heike Bickeboller Gadi Rennert Susanne Arnold Paul Brennan John KField Sanjay Shete Loic Le Marchand Olle Melander Hans Brunnstrom Geoffrey Liu Rayjean JHung Angeline Andrew Lambertus AKiemeney Shan Zienolddiny kjell grankvist Mikael Johansson Neil Caporaso Penella Woll Philip Lazarus Matthew BSchabath Melinda CAldrich Victoria LStevens Guangfu Jin David CChristiani Zhibin Hu Christopher IAmos Hongxia Ma Hongbing Shen Department of Epidemiology Center for Global HealthSchool of Public HealthNanjing Medical UniversityNanjing 211166China State Key Laboratory of Reproductive Medicine Center for Global HealthNanjing Medical UniversityNanjing 211166China Department of Bioinformatics School of Biomedical Engineering and InformaticsNanjing Medical UniversityNanjing 211166China Jiangsu Key Lab of Cancer Biomarkers Prevention and TreatmentCollaborative Innovation Center for Cancer MedicineNanjing Medical UniversityNanjing 211166China China International Cooperation Center for Environment and Human Health School of Public HealthNanjing Medical UniversityNanjing 211166China Division of Cancer Epidemiology and Genetics National Cancer InstituteBethesdaMD 20892-9304USA Department of Integrative Oncology British Columbia Cancer AgencyVancouverBC V5Z 1L3Canada Faculty of Medicine University of Oviedo and CIBERESPOviedo 33006Spain Program in Epidemiology Public Health Sciences DivisionFred Hutchinson Cancer Research CenterSeattleWA 98109-1024USA Public Health Sciences Division Swedish Cancer InstituteSeattleWA 98026USA Department of Clinical Biochemistry Copenhagen University HospitalCopenhagen DK-1017Denmark National Cancer Institute BethesdaMD 20892-9304USA Genetic Epidemiology Group International Agency for Research on CancerLyon 69372France Cancer Center Cluster Salzburg at PLUS Department of Molecular BiologyUniversity of SalzburgHeidelberg 5020Austria Institute of Medical Informatics Biometry and EpidemiologyChair of EpidemiologyLudwig Maximilians UniversityMunichBavaria 80539Germany Department of Genetic Epidemiology University Medical Center GoettingenGoettingen 37075Germany Technion Faculty of Medicine Carmel Medical CenterHaifa 3448516Israel Markey Cancer Center University of KentuckyLexingtonKY 40506-0054USA Department of Molecular and Clinical Cancer Medicine Roy Castle Lung Cancer Research ProgrammeThe University of Liverpool Institute of Translational MedicineLiverpool L697Z

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.

关键词： lung cancer genome-wide association study function annotation immune homologous recombination repair deficiency genetic heterogeneity

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Assessment of Lung Cancer Risk on the Basis of a Biomarker Panel of Circulating Proteins

Assessment of Lung Cancer Risk on the Basis of a Biomarker P...

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2019年中国肿瘤标志物学术大会暨第十三届肿瘤标志物青年科学家论坛

作者： sun,nan Florence,Guida Bantis,LeonidasE. Muller,DavidC. Li,Peng Taguchi,Ayumu Dhillon,Dilsher Kundnani,DeepaliL. Patel,NikulJ. Yan,Qingxiang Byrnes,Graham Moons,KarelG.M. Tj?nneland,Anne Panico,Salvatore Claudia ,Agnoli Vineis,Paolo Palli,Domenico Bueno-de-Mesquita,Bas Peeters,PetraH. Agudo,Antonio Huerta,JoseM. Dorronsoro,Miren Barranco,MiguelRodriguez Ardanaz,Eva Travis,RuthC. Byrne,KarlSmith Boeing,Heiner Steffen,Annika Kaaks,Rudolf Hüsing,Anika Trichopoulou,Antonia Lagiou,Pagona LaVecchia,Carlo Severi,Gianluca Boutron-Ruault,Marie-Christine Sandanger,TorkjelM. Weiderpass,Elisabete N?st,ThereseH. Tsilidis,Kostas Riboli,Elio grankvist,kjell Johansson,Mikael Goodman,GaryE. Feng,Ziding Brennan,Paul Johansson,Mattias Hanash,Samir M. The University of Texas MD Anderson Cancer Center Genetic Epidemiology Group International Agency for Research on Cancer Department of Biostatistics The University of Texas MD Anderson Cancer Center Department of Epidemiology and Biostatistics Imperial College London School of Public Health Laboratory of Population Health Max Planck Institute for Demographic Research Department of Translational Molecular Pathology The University of Texas MD Anderson Cancer Center Environment and Radiation Section International Agency for Research on Cancer Department of Epidemiology Julius Center for Health Sciences and Primary CareUniversity Medical Center Unit of Diet Genesand EnvironmentDanish Cancer Society Research Center Department of Clinical Medicine and Surgery Federico Ⅱ University Epidemiology and Prevention Unit Fondazione IRCCS Istituto Nazionale dei Tumori Molecular and Genetic Epidemiology Unit Human Genetics Foundation Cancer Risk Factors and Life-Style Epidemiology Unit Cancer Research and Prevention Institute-Istituto per lo Studio ela Prevenzione Oncologica Department for Determinants of Chronic Diseases National Institute for Public Health and the Environment Unit of Nutirition and Cancer Cancer Epidemiology Research ProgramCatalan Institute of OncologyBellvitge Institute for Biomedical Research (IDIBELL)L’Hospitalet de Llobregat Department of Epidemiology Murcia Regional Health Council Biomedical Research Institute of Murcia(IMIB-Arrixaca) Centro de Investigación Biomédica en Red Epidemiología y Salud Pública (CIBERESP) Public Health Direction and Biodonostia Research Institute-CIBERESP Escuela Andaluza de Salud Pública Instituto de Investigación Biosanitaria Hospitales Universitarios de Granada/Universidad de Granada Epidemiology Preventionand Promotion Health ServiceNavarra Public Health Institute Instituto de Investigación Sanitaria de Navarra (IdiSNA) Navarra Institute for Health Research Cancer Epidemiology Unit Nuffield Department of Population HealthUniversity of Oxford Department of Epidemi

IMPORTANCE:There is an urgent need to improve lung cancer risk assessment because current screening criteria miss a large proportion of ***:To investigate whether a lung cancer risk prediction model based on a panel of selected circulating protein biomarkers can outperform a traditional risk prediction model and current US screening criteria.

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