Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes.
About this Publication
Title
Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes.
Pubmed ID
28604730
(View this publication on the PubMed website)
Publication
Nat. Genet. 2017 Jul; Volume 49 (Issue 7): Pages 1126-1132
Authors
McKay JD, Hung RJ, Han Y, Zong X, Carreras-Torres R, Christiani DC, Caporaso NE, Johansson M, Xiao X, Li Y, Byun J, Dunning A, Pooley KA, Qian DC, Ji X, Liu G, Timofeeva MN, Bojesen SE, Wu X, Le Marchand L, ...show more Albanes D, Bickeböller H, Aldrich MC, Bush WS, Tardon A, Rennert G, Teare MD, Field JK, Kiemeney LA, Lazarus P, Haugen A, Lam S, Schabath MB, Andrew AS, Shen H, Hong YC, Yuan JM, Bertazzi PA, Pesatori AC, Ye Y, Diao N, Su L, Zhang R, Brhane Y, Leighl N, Johansen JS, Mellemgaard A, Saliba W, Haiman CA, Wilkens LR, Fernandez-Somoano A, Fernandez-Tardon G, van der Heijden HFM, Kim JH, Dai J, Hu Z, Davies MPA, Marcus MW, Brunnström H, Manjer J, Melander O, Muller DC, Overvad K, Trichopoulou A, Tumino R, Doherty JA, Barnett MP, Chen C, Goodman GE, Cox A, Taylor F, Woll P, Brüske I, Wichmann HE, Manz J, Muley TR, Risch A, Rosenberger A, Grankvist K, Johansson M, Shepherd FA, Tsao MS, Arnold SM, Haura EB, Bolca C, Holcatova I, Janout V, Kontic M, Lissowska J, Mukeria A, Ognjanovic S, Orlowski TM, Scelo G, Swiatkowska B, Zaridze D, Bakke P, Skaug V, Zienolddiny S, Duell EJ, Butler LM, Koh WP, Gao YT, Houlston RS, McLaughlin J, Stevens VL, Joubert P, Lamontagne M, Nickle DC, Obeidat M, Timens W, Zhu B, Song L, Kachuri L, Artigas MS, Tobin MD, Wain LV, SpiroMeta Consortium, Rafnar T, Thorgeirsson TE, Reginsson GW, Stefansson K, Hancock DB, Bierut LJ, Spitz MR, Gaddis NC, Lutz SM, Gu F, Johnson EO, Kamal A, Pikielny C, Zhu D, Lindströem S, Jiang X, Tyndale RF, Chenevix-Trench G, Beesley J, Bossé Y, Chanock S, Brennan P, Landi MT, Amos CI
Affiliations
- International Agency for Research on Cancer, World Health Organization, Lyon, France.
- Lunenfeld-Tanenbaum Research Institute, Sinai Health System, University of Toronto, Toronto, Ontario, Canada.
- Biomedical Data Science, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, USA.
- Department of Environmental Health, Harvard T.H. Chan School of Public Health and Massachusetts General Hospital/ Harvard Medical School, Boston, Massachusetts, USA.
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, US National Institutes of Health, Bethesda, Maryland, USA.
- Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK.
- Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Copenhagen, Denmark.
- Department of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
- Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii, USA.
- Department of Genetic Epidemiology, University Medical Center, Georg August University Göttingen, Göttingen, Germany.
- Department of Thoracic Surgery, Division of Epidemiology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
- Department of Epidemiology and Biostatistics, School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA.
- University of Oviedo and CIBERESP, Faculty of Medicine, Oviedo, Spain.
- Clalit National Cancer Control Center at Carmel Medical Center and Technion Faculty of Medicine, Haifa, Israel.
- School of Health and Related Research, University of Sheffield, Sheffield, UK.
- Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
- Departments of Health Evidence and Urology, Radboud University Medical Center, Nijmegen, the Netherlands.
- Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Spokane, Washington, USA.
- National Institute of Occupational Health, Oslo, Norway.
- British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
- Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
- Department of Epidemiology, Geisel School of Medicine, Hanover, New Hampshire, USA.
- Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, China.
- Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
- University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, USA.
- Department of Preventive Medicine, IRCCS Foundation Cà Granda Ospedale Maggiore Policlinico, Milan, Italy.
- Department of Clinical Sciences and Community Health-DISCCO, University of Milan, Milan, Italy.
- University Health Network, Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
- Department of Oncology, Herlev and Gentofte Hospital, Copenhagen University Hospital, Copenhagen, Denmark.
- Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, California, USA.
- Department of Integrative Bioscience and Biotechnology, Sejong University, Seoul, Republic of Korea.
- Department of Pathology, Lund University, Lund, Sweden.
- Faculty of Medicine, Lund University, Lund, Sweden.
- School of Public Health, St Mary's Campus, Imperial College London, London, UK.
- Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark.
- Hellenic Health Foundation, Athens, Greece.
- Molecular and Nutritional Epidemiology Unit, CSPO (Cancer Research and Prevention Centre), Scientific Institute of Tuscany, Florence, Italy.
- Program in Epidemiology, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
- Swedish Medical Group, Seattle, Washington, USA.
- Department of Oncology, University of Sheffield, Sheffield, UK.
- Institute of Epidemiology II, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
- Research Unit of Molecular Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
- Thoraxklinik at University Hospital Heidelberg, Heidelberg, Germany.
- Department of Medical Biosciences, Umeå University, Umeå, Sweden.
- Department of Radiation Sciences, Umeå University, Umeå, Sweden.
- Markey Cancer Center, University of Kentucky, Lexington, Kentucky, USA.
- Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
- Institute of Pneumology 'Marius Nasta', Bucharest, Romania.
- 2nd Faculty of Medicine, Charles University, Prague, Czech Republic.
- Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic.
- Clinical Center of Serbia, Belgrade, Serbia.
- M. Sklodowska-Curie Cancer Center, Institute of Oncology, Warsaw, Poland.
- Department of Epidemiology and Prevention, Russian N.N.Blokhin Cancer Research Centre, Moscow, Russian Federation.
- International Organization for Cancer Prevention and Research, Belgrade, Serbia.
- Department of Surgery, National Tuberculosis and Lung Diseases Research Institute, Warsaw, Poland.
- Nofer Institute of Occupational Medicine, Department of Environmental Epidemiology, Lodz, Poland.
- Department of Clinical Science, University of Bergen, Bergen, Norway.
- Unit of Nutrition and Cancer, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain.
- Duke-National University of Singapore Medical School, Singapore.
- Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China.
- The Institute of Cancer Research, London, UK.
- Public Health Ontario, Toronto, Ontario, Canada.
- American Cancer Society, Atlanta, Georgia, USA.
- Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec, Québec, Canada.
- Merck Research Laboratories, Genetics and Pharmacogenomics, Boston, Massachusetts, USA.
- University of British Columbia Centre for Heart Lung Innovation, St Paul's Hospital, Vancouver, British Columbia, Canada.
- University of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, GRIAC Research Institute, Groningen, the Netherlands.
- Genetic Epidemiology Group, Department of Health Sciences, University of Leicester, Leicester, UK.
- deCODE Genetics, Amgen, Inc., Reykjavik, Iceland.
- Behavioral and Urban Health Program, Behavioral Health and Criminal Justice Division, RTI International, Research Triangle Park, North Carolina, USA.
- Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA.
- Duncan Cancer Center, Baylor College of Medicine, Houston, Texas, USA.
- Research Computing Division, RTI International, Research Triangle Park, North Carolina, USA.
- Department of Biostatistics and Informatics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
- Fellow Program and Behavioral Health and Criminal Justice Division, RTI International, Research Triangle Park, North Carolina, USA.
- Department of Epidemiology, University of Washington, Seattle, Washington, USA.
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
- Departments of Pharmacology and Toxicology &Psychiatry, University of Toronto, Toronto, Ontario, Canada.
- Cancer Division, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Abstract
Although several lung cancer susceptibility loci have been identified, much of the heritability for lung cancer remains unexplained. Here 14,803 cases and 12,262 controls of European descent were genotyped on the OncoArray and combined with existing data for an aggregated genome-wide association study (GWAS) analysis of lung cancer in 29,266 cases and 56,450 controls. We identified 18 susceptibility loci achieving genome-wide significance, including 10 new loci. The new loci highlight the striking heterogeneity in genetic susceptibility across the histological subtypes of lung cancer, with four loci associated with lung cancer overall and six loci associated with lung adenocarcinoma. Gene expression quantitative trait locus (eQTL) analysis in 1,425 normal lung tissue samples highlights RNASET2, SECISBP2L and NRG1 as candidate genes. Other loci include genes such as a cholinergic nicotinic receptor, CHRNA2, and the telomere-related genes OFBC1 and RTEL1. Further exploration of the target genes will continue to provide new insights into the etiology of lung cancer.
Related CDAS Studies
Related CDAS Projects
- 2007-0004: A Whole Genome Association Study (WGAS) of Lung Cancer and Smoking (Neil Caporaso - 2007)