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Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33.

About this Publication
Title
Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33.
Pubmed ID
25027329 (View this publication on the PubMed website)
Publication
Hum. Mol. Genet. 2014 Dec; Volume 23 (Issue 24): Pages 6616-33
Authors
Wang Z, Zhu B, Zhang M, Parikh H, Jia J, Chung CC, Sampson JN, Hoskins JW, Hutchinson A, Burdette L, Ibrahim A, Hautman C, Raj PS, Abnet CC, Adjei AA, Ahlbom A, Albanes D, Allen NE, Ambrosone CB, Aldrich M, ...show more Amiano P, Amos C, Andersson U, Andriole G, Andrulis IL, Arici C, Arslan AA, Austin MA, Baris D, Barkauskas DA, Bassig BA, Beane Freeman LE, Berg CD, Berndt SI, Bertazzi PA, Biritwum RB, Black A, Blot W, Boeing H, Boffetta P, Bolton K, Boutron-Ruault MC, Bracci PM, Brennan P, Brinton LA, Brotzman M, Bueno-de-Mesquita HB, Buring JE, Butler MA, Cai Q, Cancel-Tassin G, Canzian F, Cao G, Caporaso NE, Carrato A, Carreon T, Carta A, Chang GC, Chang IS, Chang-Claude J, Che X, Chen CJ, Chen CY, Chen CH, Chen C, Chen KY, Chen YM, Chokkalingam AP, Chu LW, Clavel-Chapelon F, Colditz GA, Colt JS, Conti D, Cook MB, Cortessis VK, Crawford ED, Cussenot O, Davis FG, De Vivo I, Deng X, Ding T, Dinney CP, Di Stefano AL, Diver WR, Duell EJ, Elena JW, Fan JH, Feigelson HS, Feychting M, Figueroa JD, Flanagan AM, Fraumeni JF, Freedman ND, Fridley BL, Fuchs CS, Gago-Dominguez M, Gallinger S, Gao YT, Gapstur SM, Garcia-Closas M, Garcia-Closas R, Gastier-Foster JM, Gaziano JM, Gerhard DS, Giffen CA, Giles GG, Gillanders EM, Giovannucci EL, Goggins M, Gokgoz N, Goldstein AM, Gonzalez C, Gorlick R, Greene MH, Gross M, Grossman HB, Grubb R, Gu J, Guan P, Haiman CA, Hallmans G, Hankinson SE, Harris CC, Hartge P, Hattinger C, Hayes RB, He Q, Helman L, Henderson BE, Henriksson R, Hoffman-Bolton J, Hohensee C, Holly EA, Hong YC, Hoover RN, Hosgood HD, Hsiao CF, Hsing AW, Hsiung CA, Hu N, Hu W, Hu Z, Huang MS, Hunter DJ, Inskip PD, Ito H, Jacobs EJ, Jacobs KB, Jenab M, Ji BT, Johansen C, Johansson M, Johnson A, Kaaks R, Kamat AM, Kamineni A, Karagas M, Khanna C, Khaw KT, Kim C, Kim IS, Kim JH, Kim YH, Kim YC, Kim YT, Kang CH, Jung YJ, Kitahara CM, Klein AP, Klein R, Kogevinas M, Koh WP, Kohno T, Kolonel LN, Kooperberg C, Kratz CP, Krogh V, Kunitoh H, Kurtz RC, Kurucu N, Lan Q, Lathrop M, Lau CC, Lecanda F, Lee KM, Lee MP, Le Marchand L, Lerner SP, Li D, Liao LM, Lim WY, Lin D, Lin J, Lindstrom S, Linet MS, Lissowska J, Liu J, Ljungberg B, Lloreta J, Lu D, Ma J, Malats N, Mannisto S, Marina N, Mastrangelo G, Matsuo K, McGlynn KA, McKean-Cowdin R, McNeill LH, McWilliams RR, Melin BS, Meltzer PS, Mensah JE, Miao X, Michaud DS, Mondul AM, Moore LE, Muir K, Niwa S, Olson SH, Orr N, Panico S, Park JY, Patel AV, Patino-Garcia A, Pavanello S, Peeters PH, Peplonska B, Peters U, Petersen GM, Picci P, Pike MC, Porru S, Prescott J, Pu X, Purdue MP, Qiao YL, Rajaraman P, Riboli E, Risch HA, Rodabough RJ, Rothman N, Ruder AM, Ryu JS, Sanson M, Schned A, Schumacher FR, Schwartz AG, Schwartz KL, Schwenn M, Scotlandi K, Seow A, Serra C, Serra M, Sesso HD, Severi G, Shen H, Shen M, Shete S, Shiraishi K, Shu XO, Siddiq A, Sierrasesumaga L, Sierri S, Loon Sihoe AD, Silverman DT, Simon M, Southey MC, Spector L, Spitz M, Stampfer M, Stattin P, Stern MC, Stevens VL, Stolzenberg-Solomon RZ, Stram DO, Strom SS, Su WC, Sund M, Sung SW, Swerdlow A, Tan W, Tanaka H, Tang W, Tang ZZ, Tardon A, Tay E, Taylor PR, Tettey Y, Thomas DM, Tirabosco R, Tjonneland A, Tobias GS, Toro JR, Travis RC, Trichopoulos D, Troisi R, Truelove A, Tsai YH, Tucker MA, Tumino R, Van Den Berg D, Van Den Eeden SK, Vermeulen R, Vineis P, Visvanathan K, Vogel U, Wang C, Wang C, Wang J, Wang SS, Weiderpass E, Weinstein SJ, Wentzensen N, Wheeler W, White E, Wiencke JK, Wolk A, Wolpin BM, Wong MP, Wrensch M, Wu C, Wu T, Wu X, Wu YL, Wunder JS, Xiang YB, Xu J, Yang HP, Yang PC, Yatabe Y, Ye Y, Yeboah ED, Yin Z, Ying C, Yu CJ, Yu K, Yuan JM, Zanetti KA, Zeleniuch-Jacquotte A, Zheng W, Zhou B, Mirabello L, Savage SA, Kraft P, Chanock SJ, Yeager M, Landi MT, Shi J, Chatterjee N, Amundadottir LT
Affiliations
  • Division of Cancer Epidemiology and Genetics, Cancer Genomics Research Laboratory, National Cancer Institute, Division of Cancer Epidemiology and Genetics, SAIC-Frederick, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
  • Division of Cancer Epidemiology and Genetics.
  • Korle Bu Teaching Hospital, PO BOX 77, Accra, Ghana, University of Ghana Medical School, PO Box 4236, Accra, Ghana.
  • Unit of Epidemiology, Institute of Environmental Medicine.
  • Clinical Trial Service Unit and Epidemiological Studies Unit, University of Oxford, Oxford, UK.
  • Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY, USA.
  • Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA.
  • Public Health Division of Gipuzkoa, Basque Regional Health Department, San Sebastian, Spain, CIBERESP, CIBER Epidemiologia y Salud Publica, Madrid, Spain.
  • Geisel School of Medicine at Dartmouth, Hanover, NH, USA.
  • Department of Radiation Sciences, Oncology.
...show more
  • Division of Urologic Surgery, Washington University School of Medicine, St Louis, MO, USA.
  • Litwin Centre for Cancer Genetics, Samuel Lunenfeld Research Institute, Mt Sinai Hospital, University of Toronto, Toronto, ON, Canada.
  • Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Italy.
  • Department of Obstetrics and Gynecology and Department of Population Health, New York University School of Medicine, New York, NY, USA, New York University Cancer Institute, New York, NY, USA.
  • Department of Epidemiology, University of Washington, Seattle, WA, USA.
  • Department of Preventive Medicine, Biostatistics Division, Keck School of Medicine and.
  • Division of Cancer Epidemiology and Genetics, Division of Environmental Health Sciences, Yale School of Public Health, New Haven, Connecticut, USA.
  • Division of Cancer Prevention.
  • Department of Clinical Sciences and Community Health, University of Milan, Department of Preventive Medicine, Fondazione IRCCS Ca' Granda Policlinico Hospital, Milan, Italy.
  • Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA, International Epidemiology Institute, Rockville, MD, USA.
  • Department of Epidemiology, German Institute of Human Nutrition, Potsdam-Rehbruecke, Germany.
  • Institute for Translational Epidemiology, Hematology and Medical Oncology, Mount Sinai Hospital School of Medicine, New York, NY, USA.
  • Division of Cancer Epidemiology and Genetics, Department of Oncology, University of Cambridge, Cambridge CB2 2RE, UK.
  • Institut National de la Sante et de la Recherche Medicale (INSERM) and Institut Gustave Roussy, Villejuif, France.
  • Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA.
  • International Agency for Research on Cancer (IARC-WHO), Lyon, France.
  • Westat, Rockville, MD, USA.
  • National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands, Department of Gastroenterology and Hepatology, University Medical Centre Utrecht, Utrecht, The Netherlands.
  • Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, USA.
  • Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, Cincinnati, OH, USA.
  • CeRePP, Paris, France, UPMC Univ Paris 06, GRC n°5, ONCOTYPE-URO, Paris, France.
  • Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Department of Epidemiology, Second Military Medical University, Shanghai, China.
  • Medical Oncology Department, Hospital Ramón y Cajal, Madrid, Spain.
  • Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
  • National Institute of Cancer Research.
  • Department of Abdominal Surgery and.
  • Genomics Research Center, Academia Sinica, Taipei, Taiwan, Graduate Institute of Epidemiology, College of Public Health, National Taiwan University, Taipei, Taiwan.
  • Cancer Center, China Medical University Hospital, Taipei, Taiwan.
  • Program in Molecular and Genetic Epidemiology.
  • Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
  • Department of Epidemiology and Public Health, Yong Loo Lin School of Medicine and Chest Department, Taipei Veterans General Hospital, Taipei, Taiwan, College of Medical Science and Technology, Taipei Medical University, Taiwan.
  • School of Public Health, University of California, Berkeley, CA, USA.
  • Cancer Prevention Institute of California, Fremont, CA, USA.
  • Inserm, Centre for Research in Epidemiology and Population Health (CESP), Villejuif, France.
  • Washington University School of Medicine, St Louis, MO, USA.
  • Urologic Oncology, University of Colorado, Aurora, CO, USA.
  • CeRePP, Paris, France, AP-HP, Department of Urology, Tenon Hospital, GHU-Est, Paris, France, UPMC Univ Paris 06, GRC n°5, ONCOTYPE-URO, Paris, France.
  • Department of Public Health Sciences, School of Public Health, University of Alberta, Edmonton, AB, Canada T6G 2R3.
  • Program in Molecular and Genetic Epidemiology, Department of Medicine, Channing Division of Network Medicine and Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • Shanxi Cancer Hospital, Taiyuan, Shanxi, People's Republic of China.
  • Department of Urology.
  • Service de Neurologie Mazarin, GH Pitie-Salpetriere, APHP, and UMR 975 INSERM-UPMC, CRICM, Paris, France.
  • Epidemiology Research Program, American Cancer Society, Atlanta, GA, USA.
  • Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program, Bellvitge Biomedical Research Institute, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain.
  • Epidemiology and Genomics Research Program, Division of Cancer Control and Population Sciences, Bethesda, MD, USA.
  • Shanghai Cancer Institute, Shanghai, People's Republic of China.
  • Institute for Health Research, Kaiser Permanente, Denver, CO, USA.
  • UCL Cancer Institute, Huntley Street, London WC1E 6BT, UK, Royal National Orthopaedic Hospital NHS Trust, Stanmore, Middlesex HA7 4LP, UK.
  • Department of Biostatistics, University of Kansas Medical Center, Kansas City, KS, USA.
  • Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA, Channing Laboratory, Department of Medicine.
  • Genomic Medicine Group, Galician Foundation of Genomic Medicine, Complejo Hospitalario Universitario de Santiago, Servicio Galego de Saude (SERGAS), Instituto de Investigación Sanitaria de Santiago (IDIS), Santiago de Compostela, Spain.
  • Samuel Lunenfeld Research Institute and.
  • Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotaong University School of Medicine, Shanghai, China.
  • Division of Cancer Epidemiology and Genetics, Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, UK.
  • Unidad de Investigación, Hospital Universitario de Canarias, La Laguna, Spain.
  • Nationwide Children's Hospital, and The Ohio State University Department of Pathology and Pediatrics, Columbus, OH, USA.
  • Division of Preventive Medicine, Department of Medicine and Division of Aging, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA, Massachusetts Veteran's Epidemiology, Research and Information Center, Geriatric Research Education and Clinical Center, Veterans Affairs Boston Healthcare System, Boston, MA, USA.
  • Office of Cancer Genomics, Department of Health and Human Services, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • Information Management Services Inc., Calverton, MD, USA.
  • Cancer Epidemiology Centre, The Cancer Council Victoria & Centre for Molecular, Environmental, Genetic, and Analytic Epidemiology, The University of Melbourne, Victoria, Australia.
  • Division of Cancer Control and Population Sciences and.
  • Program in Molecular and Genetic Epidemiology, Department of Nutrition and.
  • Department of Oncology, Department of Pathology and Department of Medicine, The Sol Goldman Pancreatic Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.
  • Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology (ICO), Barcelona, Spain.
  • Albert Einstein College of Medicine, The Children's Hospital at Montefiore, Bronx, NY, USA.
  • Department of Laboratory Medicine and Pathology, School of Medicine, University of Minnesota, Minneapolis, MN, USA.
  • Department of Urology, Washington University School of Medicine, St Louis, MO, USA.
  • Department of Epidemiology.
  • Department of Epidemiology, School of Public Health, China Medical University, Shenyang, China.
  • Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Department of Public Health and Clinical Medicine/Nutritional Research.
  • Channing Laboratory, Department of Medicine.
  • Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
  • Laboratory of Experimental Oncology, Orthopaedic Rizzoli Institute, Bologna, Italy.
  • Division of Cancer Epidemiology and Genetics, Department of Population Health, New York University Langone Medical Center and Department of Environmental Medicine, New York University Langone Medical Center, New York University Cancer Institute, New York, NY, USA.
  • Center for Cancer Research and.
  • Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
  • Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
  • Institute of Environmental Medicine, Seoul National University Medical Research Center, Seoul, Republic of Korea, Department of Preventive Medicine and.
  • Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA.
  • Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences and Taiwan Lung Cancer Tissue/Specimen Information Resource Center, National Health Research Institutes, Zhunan, Taiwan.
  • Cancer Prevention Institute of California, Fremont, CA, USA, Stanford Cancer Institute, Stanford University, Stanford, CA, USA.
  • Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences and.
  • Department of Epidemiology and Biostatistics, Cancer Center, Nanjing Medical University, Nanjing, China.
  • Program in Molecular and Genetic Epidemiology, Department of Medicine, Channing Division of Network Medicine and Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan.
  • Cancer Genomics Research Laboratory, National Cancer Institute, Division of Cancer Epidemiology and Genetics, SAIC-Frederick, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA, Cancer Genomics Research Laboratory, National Cancer Institute, Division of Cancer Epidemiology and Genetics, SAIC-Frederick, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA, Bioinformed, LLC, Gaithersburg, MD, USA.
  • Department of Oncology, Finsen Center, Rigshospitalet, Copenhagen, Denmark, Unit of Survivorship, Danish Cancer Society Research Center, Copenhagen, Denmark.
  • International Agency for Research on Cancer (IARC-WHO), Lyon, France, Department of Public Health and Clinical Medicine.
  • Vermont Cancer Registry, Burlington, VT, USA.
  • Group Health Research Institute, Seattle, WA, USA.
  • School of Clinical Medicine, University of Cambridge, UK.
  • Department of Biochemistry and Department of Cell Biology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
  • Institute of Environmental Medicine, Seoul National University Medical Research Center, Seoul, Republic of Korea.
  • Genomic Research Center for Lung and Breast/Ovarian Cancers, Korea University Anam Hospital, Seoul, Republic of Korea, Department of Internal Medicine and Division of Brain and Division of Oncology/Hematology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea.
  • Lung and Esophageal Cancer Clinic, Chonnam National University Hwasun Hospital, Hwasun-eup, Republic of Korea.
  • Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
  • Department of Oncology, Department of Pathology and Department of Medicine, The Sol Goldman Pancreatic Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA, Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
  • Department of Medicine and.
  • Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain, CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain, National School of Public Health, Athens, Greece.
  • Duke-NUS Graduate Medical School, Singapore, Singapore, Saw Swee Hock School of Public Health, National University of Singapore, Singapore.
  • Division of Genome Biology, National Cancer Center Research Institute, Tokyo, Japan.
  • Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA.
  • Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
  • Division of Genome Biology, National Cancer Center Research Institute, Tokyo, Japan, Department of Respiratory Medicine, Mitsui Memorial Hospital, Tokyo, Japan.
  • Department of Pediatric Oncology, A.Y. Ankara Oncology Training and Research Hospital, Yenimahalle- Ankara, Turkey.
  • Centre National de Genotypage, IG/CEA, Evry Cedex, France, Centre d'Étude du Polymorphism Humain (CEPH), Paris, France.
  • Texas Children's Cancer and Hematology Centers.
  • Department of Pediatrics, University Clinic of Navarra, Universidad de Navarra, Pamplona, Spain.
  • Department of Preventive Medicine and Department of Environmental Health, Korea National Open University, Seoul, Republic of Korea.
  • Scott Department of Urology and.
  • Department of Gastrointestinal Medical Oncology.
  • Saw Swee Hock School of Public Health, National University of Singapore, Singapore.
  • State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
  • Department of Cancer Epidemiology and Prevention, Maria Sklodowska-Curie Cancer Center and Institute of Oncology, Warsaw, Poland.
  • Human Genetics Division, Genome Institute of Singapore, Singapore, School of Life Sciences, Anhui Medical University, Hefei, China.
  • Department of Surgical and Perioperative Sciences, Urology and Andrology and.
  • CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain.
  • Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China, State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China.
  • Department of Medicine, Channing Division of Network Medicine and Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • Centro Nacional de Investigaciones Oncologicas, Melchor Fernández Almagro, 3, Madrid E-28029, Spain.
  • National Institute for Health and Welfare, Helsinki, Finland.
  • Lucile Packard Children's Hospital, Stanford University, Palo Alto, CA, USA.
  • Department of Cardiac, Thoracic and Vascular Sciences, University of Padova, Padua, Italy.
  • Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan, Department of Preventive Medicine, Kyushu University Faculty of Medical Scicence, Fukuoka, Japan.
  • Department of Health Disparities Research, Division of OVP, Cancer Prevention and Population Sciences, and Center for Community-Engaged Translational Research, Duncan Family Institute and.
  • Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
  • Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan, China.
  • Department of Epidemiology, Division of Biology and Medicine, Brown University, Providence, RI, USA.
  • Health Sciences Research Institute, University of Warwick, Coventry, UK.
  • Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
  • Complex Traits Genetics Team and.
  • Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy.
  • Department of Biochemistry and Department of Cell Biology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea, Lung Cancer Center, Kyungpook National University Medical Center, Daegu, Republic of Korea.
  • Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, Utrecht, The Netherlands, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
  • Nofer Institute of Occupational Medicine, Lodz, Poland.
  • Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA, Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
  • Department of Epidemiology, Cancer Institute (Hospital), Chinese Academy of Medical Sciences, Beijing, People's Republic of China.
  • Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
  • Yale School of Public Health, New Haven, CT, USA.
  • Department of Internal Medicine, Inha University College of Medicine, Incheon, Korea.
  • Karmanos Cancer Institute and Department of Oncology and.
  • Karmanos Cancer Institute and Department of Family Medicine and Public Health Sciences, Wayne State University School of Medicine, Detroit, MI, USA.
  • Maine Cancer Registry, Augusta, ME, USA.
  • Centre for Research in Occupational Health, Universitat Pompeu Fabra, Barcelona, Spain, CIBER of Epidemiology and Public Health (CIBERESP).
  • Department of Biostatistics, MD Anderson Cancer Center, Houston, TX, USA.
  • Department of Genomics of Common Disease, School of Public Health, Imperial College London, London, UK.
  • Nutritional Epidemiology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
  • Department of Surgery, Division of Cardiothoracic Surgery, Queen Mary Hospital, Hong Kong, China.
  • Department of Neurosurgery, University of Bonn Medical Center, Bonn, Germany.
  • Department of Pathology, The University of Melbourne, Melbourne, VIC, Australia.
  • University of Minnesota, Minneapolis, MN, USA.
  • Dan L. Duncan Center, Baylor College of Medicine, Houston, TX, USA.
  • Department of Epidemiology, Division of Cancer Prevention and Population Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Department of Internal Medicine, National Cheng Kung University Hospital and College of Medicine, Tainan, Taiwan.
  • Department of Surgical and Perioperative Sciences/Surgery, Umeå University, Umeå, Sweden.
  • Department of Thoracic and Cardiovascular Surgery, Seoul St Mary's Hospital, Seoul, South Korea.
  • Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, UK, Division of Breast Cancer Research, Institute of Cancer Research, London, UK.
  • Instituto Universitario de Oncología, Universidad de Oviedo, Oviedo, Spain.
  • Sir Peter MacCallum Department of Oncology, University of Melbourne, St Andrew's Place, East Melbourne, VIC, Australia.
  • Royal National Orthopaedic Hospital NHS Trust, Stanmore, Middlesex HA7 4LP, UK.
  • Danish Cancer Society Research Center, Copenhagen, Denmark.
  • Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA.
  • Department of Pulmonary Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan.
  • Cancer Registry Associazione Iblea Ricerca Epidemiologica, Onlus and Asp Ragusa, Ragusa Italy.
  • Kaiser Permanente Northern California, Oakland, CA, USA.
  • Division of Environmental Epidemiology, Institute for Risk Assessment Sciences (IRAS), Utrecht University, Utrecht, The Netherlands.
  • Imperial College, London, UK, Human Genetics Foundation (HuGeF), Torino Italy.
  • National Research Centre for the Working Environment, Copenhagen, Denmark, National Food Institute, Technical University of Denmark, Soborg, Denmark.
  • Division of Cancer Epidemiology and Genetics, Cancer Genomics Research Laboratory, National Cancer Institute, Division of Cancer Epidemiology and Genetics, SAIC-Frederick, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA, Department of Biochemistry and Centre for Genomic Sciences, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
  • Division of Cancer Etiology, Department of Population Sciences, City of Hope and the Beckman Research Institute, Duarte, CA, USA.
  • Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway, Department of Research, Cancer Registry of Norway, Oslo, Norway, Department of Medical Epidemiology and Biostatistics and Samfundet Folkhälsan, Helsinki, Finland.
  • University of California San Francisco, San Francisco, CA, USA.
  • Unit of Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
  • Department of Pathology and.
  • Guangdong Lung Cancer Institute, Medical Research Center and Cancer Center of Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
  • School of Public Health, Li Ka Shing (LKS) Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
  • Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital and.
  • University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA and.
  • Department of Population Health, New York University School of Medicine, New York, NY, USA, New York University Cancer Institute, New York, NY, USA.
  • Program in Molecular and Genetic Epidemiology, Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA.
  • Division of Cancer Epidemiology and Genetics, amundadottirl@mail.nih.gov.
Abstract

Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.

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