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A Genome-wide Association Study of Lung Cancer Identifies a Region of Chromosome 5p15 Associated with Risk for Adenocarcinoma |
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| Authors: | Maria Teresa Landi Nilanjan Chatterjee Lynn R Goldin Melissa Rotunno Kevin Jacobs Meredith Yeager Qizhai Li Dario Consonni Sholom Wacholder Ryan Diver Jarmo Virtamo Zhaoming Wang Kimberly F Doheny Cathy Laurie Rayjean Hung James D McKay John McLaughlin Ming-Sound Tsao Yufei Wang Lars Vatten Egil Arnesen Christine Bouchard Tonu Vooder Kristian Välk Chu Chen Patrick Sulem Thorunn Rafnar Wiebke Sauter Heike Bickeböller Jenny Chang-Claude Kari Stefansson Christopher I Amos Sharon A Savage Margaret A Tucker Neil E Caporaso |
| Institution: | 1 Division of Cancer Epidemiology, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA 2 Information Management Services, Inc., Rockville, MD 20852, USA 3 Center for Health Sciences, Molecular Genetic Program, SRI International, Menlo Park, CA 94025, USA 4 Key Laboratory of Systems and Control, Academy of Mathematics and System Science, Chinese Academy of Science, Beijing 100190, P.R. China 5 Unit of Epidemiology, Fondazione Istituto di Ricevero e Cura a Carattere Scientifico, Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena and Department of Occupational and Environmental Health, University of Milan, Milan, 20122, Italy 6 American Cancer Society, Epidemiology and Surveillance Research, Atlanta, GA 30301, USA 7 Hubert H. Humphrey Cancer Center, Robbinsdale, University of Minnesota, Minneapolis, MN 55455, USA 8 Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, 00280, Finland 9 Center for Inherited Disease Research, Institute of Genetic Medicine, Johns Hopkins School of Medicine, Baltimore, MD 21224, USA 10 Department of Biostatistics, University of Washington, Seattle, WA 98195, USA 11 International Agency for Research on Cancer, Lyon, 69372, France 12 Samuel Lunenfeld Research Institute, Division of Epidemiology, Dalla Lana School of Public Health, University of Toronto, Toronto, ON M5T 3L9, Canada 13 Fondation Jean Dausset-Centre d'Etude du Polymorphisme Humain (CEPH), Paris, 75010, France 14 Department of Pathology, University Health Network, Princess Margaret Hospital and University of Toronto, Toronto, ON M5T 3L9, Canada 15 Department of Epidemiology, M.D. Anderson Cancer Center, University of Texas, Houston, TX 77030, USA 16 Section of Cancer Genetics, Institute of Cancer Research, Surrey, SM2 5NG, UK 17 Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, N-7489, Norway 18 Department of Community Medicine, University of Tromso, Tromso, N-9037, Norway 19 INSERM and Fondation Jean Dausset-CEPH, Paris, 75010, France 20 Geneva Cancer Registry, Geneva, 1205, Switzerland 21 Institute of Molecular and Cell Biology and Estonian Genome Project of the University of Tartu, Estonian Biocentre, Tartu, 51010, Estonia 22 Roy Castle Lung Cancer Research Program, The University of Liverpool Cancer Research Center, Liverpool, L3 97A, UK 23 Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA 24 deCODE Genetics, Reykjavik, 101, Iceland 25 Department of Oncology, University of Cambridge, Cambridge, CB2 2RE, UK 26 Institute of Epidemiology, Helmholtz Center Munich, German Research Center for Environmental Health, Neuherberg, D-85764, Germany 27 Institute of Medical Informatics, Biometry and Epidemiology, Chair of Epidemiology, Ludwig Maximilians University, 81377 Munich, Germany 28 Klinikum Grosshadern, Ludwig Maximilians University, 81377 Munich, Germany 29 Department of Genetic Epidemiology, University of Göttingen Medical School, Göttingen, D-37073, Germany 30 Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center, Heidelberg, D-69120, Germany |
| Abstract: | Three genetic loci for lung cancer risk have been identified by genome-wide association studies (GWAS), but inherited susceptibility to specific histologic types of lung cancer is not well established. We conducted a GWAS of lung cancer and its major histologic types, genotyping 515,922 single-nucleotide polymorphisms (SNPs) in 5739 lung cancer cases and 5848 controls from one population-based case-control study and three cohort studies. Results were combined with summary data from ten additional studies, for a total of 13,300 cases and 19,666 controls of European descent. Four studies also provided histology data for replication, resulting in 3333 adenocarcinomas (AD), 2589 squamous cell carcinomas (SQ), and 1418 small cell carcinomas (SC). In analyses by histology, rs2736100 (TERT), on chromosome 5p15.33, was associated with risk of adenocarcinoma (odds ratio OR] = 1.23, 95% confidence interval CI] = 1.13–1.33, p = 3.02 × 10−7), but not with other histologic types (OR = 1.01, p = 0.84 and OR = 1.00, p = 0.93 for SQ and SC, respectively). This finding was confirmed in each replication study and overall meta-analysis (OR = 1.24, 95% CI = 1.17–1.31, p = 3.74 × 10−14 for AD; OR = 0.99, p = 0.69 and OR = 0.97, p = 0.48 for SQ and SC, respectively). Other previously reported association signals on 15q25 and 6p21 were also refined, but no additional loci reached genome-wide significance. In conclusion, a lung cancer GWAS identified a distinct hereditary contribution to adenocarcinoma. |
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