Genome-wide association study identifies multiple susceptibility loci for pancreatic cancer

Brian M Wolpin¹, Cosmeri Rizzato², Peter Kraft³, Charles Kooperberg⁴, Gloria M Petersen⁵, Zhaoming Wang⁶, Alan A Arslan⁷, Laura Beane-Freeman⁸, Paige M Bracci⁹, Julie Buring¹⁰, Federico Canzian¹¹, Eric J Duell¹², Steven Gallinger¹³, Graham G Giles¹⁴, Gary E Goodman¹⁵, Phyllis J Goodman¹⁶, Eric J Jacobs¹⁷, Aruna Kamineni¹⁸, Alison P Klein¹⁹, Laurence N Kolonel²⁰, Matthew H Kulke²¹, Donghui Li²², Núria Malats²³, Sara H Olson²⁴, Harvey A Risch²⁵, Howard D Sesso²⁶, Kala Visvanathan²⁷, Emily White²⁸, Wei Zheng²⁹, Christian C Abnet⁸, Demetrius Albanes⁸, Gabriella Andreotti⁸, Melissa A Austin³⁰, Richard Barfield³¹, Daniela Basso³², Sonja I Berndt⁸, Marie-Christine Boutron-Ruault³³, Michelle Brotzman³⁴, Markus W Büchler³⁵, H Bas Bueno-de-Mesquita³⁶, Peter Bugert³⁷, Laurie Burdette⁶, Daniele Campa³⁸, Neil E Caporaso⁸, Gabriele Capurso³⁹, Charles Chung⁶, Michelle Cotterchio⁴⁰, Eithne Costello⁴¹, Joanne Elena⁴², Niccola Funel⁴³, J Michael Gaziano⁴⁴, Nathalia A Giese³⁵, Edward L Giovannucci⁴⁵, Michael Goggins⁴⁶, Megan J Gorman²¹, Myron Gross⁴⁷, Christopher A Haiman⁴⁸, Manal Hassan²², Kathy J Helzlsouer⁴⁹, Brian E Henderson⁵⁰, Elizabeth A Holly⁹, Nan Hu⁸, David J Hunter⁵¹, Federico Innocenti⁵², Mazda Jenab⁵³, Rudolf Kaaks³⁸, Timothy J Key⁵⁴, Kay-Tee Khaw⁵⁵, Eric A Klein⁵⁶, Manolis Kogevinas⁵⁷, Vittorio Krogh⁵⁸, Juozas Kupcinskas⁵⁹, Robert C Kurtz⁶⁰, Andrea LaCroix¹⁵, Maria T Landi⁸, Stefano Landi⁶¹, Loic Le Marchand⁶², Andrea Mambrini⁶³, Satu Mannisto⁶⁴, Roger L Milne⁶⁵, Yusuke Nakamura⁶⁶, Ann L Oberg⁶⁷, Kouros Owzar⁶⁸, Alpa V Patel¹⁷, Petra H M Peeters⁶⁹, Ulrike Peters⁷⁰, Raffaele Pezzilli⁷¹, Ada Piepoli⁷², Miquel Porta⁷³, Francisco X Real⁷⁴, Elio Riboli⁷⁵, Nathaniel Rothman⁸, Aldo Scarpa⁷⁶, Xiao-Ou Shu²⁹, Debra T Silverman⁸, Pavel Soucek⁷⁷, Malin Sund⁷⁸, Renata Talar-Wojnarowska⁷⁹, Philip R Taylor⁸, George E Theodoropoulos⁸⁰, Mark Thornquist¹⁵, Anne Tjønneland⁸¹, Geoffrey S Tobias⁸, Dimitrios Trichopoulos⁸², Pavel Vodicka⁸³, Jean Wactawski-Wende⁸⁴, Nicolas Wentzensen⁸, Chen Wu⁸⁵, Herbert Yu⁶², Kai Yu⁸, Anne Zeleniuch-Jacquotte⁸⁶, Robert Hoover⁸, Patricia Hartge⁸⁷, Charles Fuchs⁸⁸, Stephen J Chanock⁸⁹, Rachael S Stolzenberg-Solomon⁸⁷, Laufey T Amundadottir⁸⁷

Affiliations

¹ 1] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA. [2] Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. [3].
² 1] Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany. [2].
³ 1] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA. [2] Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, USA. [3].
⁴ 1] Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA. [2].
⁵ 1] Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA. [2].
⁶ 1] Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. [2] Cancer Genomics Research Laboratory, National Cancer Institute, Division of Cancer Epidemiology and Genetics, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA.
⁷ 1] Department of Obstetrics and Gynecology, New York University School of Medicine, New York, New York, USA. [2] Department of Environmental Medicine, New York University School of Medicine, New York, New York, USA. [3] New York University Cancer Institute, New York, New York, USA.
⁸ Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
⁹ Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, USA.
¹⁰ 1] Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. [2] Division of Aging, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
¹¹ Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
¹² Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain.
¹³ Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
¹⁴ 1] Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria, Australia. [2] Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia. [3] Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.
¹⁵ Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
¹⁶ Southwest Oncology Group Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
¹⁷ Epidemiology Research Program, American Cancer Society, Atlanta, Georgia, USA.
¹⁸ Group Health Research Institute, Seattle, Washington, USA.
¹⁹ 1] Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. [2] Department of Epidemiology, Bloomberg School of Public Health, Baltimore, Maryland, USA.
²⁰ The Cancer Research Center of Hawaii (retired), Honolulu, Hawaii, USA.
²¹ Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
²² Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
²³ Genetic and Molecular Epidemiology Group, CNIO-Spanish National Cancer Research Centre, Madrid, Spain.
²⁴ Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
²⁵ Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut, USA.
²⁶ 1] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA. [2] Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. [3] Division of Aging, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
²⁷ Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
²⁸ 1] Fred Hutchinson Cancer Research Center, Seattle, Washington, USA. [2] Department of Epidemiology, University of Washington, Seattle, Washington, USA.
²⁹ 1] Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA. [2] Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
³⁰ Department of Epidemiology, University of Washington, Seattle, Washington, USA.
³¹ Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, USA.
³² Department of Laboratory Medicine, University Hospital of Padova, Padua, Italy.
³³ 1] INSERM, Centre for Research in Epidemiology and Population Health (CESP), Nutrition, Hormones and Women's Health Team, Villejuif, France. [2] University Paris Sud, UMRS 1018, Villejuif, France. [3] Institut Gustave Roussy (IGR), Villejuif, France.
³⁴ Westat, Rockville, Maryland, USA.
³⁵ Department of General Surgery, University Hospital Heidelberg, Heidelberg, Germany.
³⁶ 1] National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands. [2] Department of Gastroenterology and Hepatology, University Medical Centre Utrecht, Utrecht, the Netherlands. [3] Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands.
³⁷ Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, Heidelberg University, German Red Cross Blood Service Baden-Württemberg-Hessen, Mannheim, Germany.
³⁸ Division of Cancer Epidemiology, DKFZ, Heidelberg, Germany.
³⁹ Digestive and Liver Disease Unit, 'Sapienza' University of Rome, Rome, Italy.
⁴⁰ 1] Cancer Care Ontario, University of Toronto, Toronto, Ontario, Canada. [2] Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
⁴¹ National Institute for Health Research Liverpool Pancreas Biomedical Research Unit, University of Liverpool, Liverpool, UK.
⁴² Division of Cancer Control and Population Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
⁴³ Department of Surgery, Unit of Experimental Surgical Pathology, University Hospital of Pisa, Pisa, Italy.
⁴⁴ 1] Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. [2] Division of Aging, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. [3] Massachusetts Veteran's Epidemiology, Research and Information Center, Geriatric Research Education and Clinical Center, Veterans Affairs Boston Healthcare System, Boston, Massachusetts, USA.
⁴⁵ 1] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA. [2] Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. [3] Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA.
⁴⁶ 1] Department of Pathology, Sidney Kimmel Cancer Center and Johns Hopkins University, Baltimore, Maryland, USA. [2] Department of Medicine, Sidney Kimmel Cancer Center and Johns Hopkins University, Baltimore, Maryland, USA. [3] Department of Oncology, Sidney Kimmel Cancer Center and Johns Hopkins University, Baltimore, Maryland, USA.
⁴⁷ Laboratory of Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota, USA.
⁴⁸ Preventive Medicine, University of Southern California, Los Angeles, California, USA.
⁴⁹ Prevention and Research Center, Mercy Medical Center, Baltimore, Maryland, USA.
⁵⁰ Cancer Prevention, University of Southern California, Los Angeles, California, USA.
⁵¹ 1] Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. [2] Harvard School of Public Health, Boston, Massachusetts, USA. [3] Harvard Medical School, Boston, Massachusetts, USA.
⁵² The University of North Carolina Eshelman School of Pharmacy, Center for Pharmacogenomics and Individualized Therapy, Lineberger Comprehensive Cancer Center, School of Medicine, Chapel Hill, North Carolina, USA.
⁵³ International Agency for Research on Cancer, Lyon, France.
⁵⁴ Cancer Epidemiology Unit, University of Oxford, Oxford, UK.
⁵⁵ School of Clinical Medicine, University of Cambridge, Cambridge, UK.
⁵⁶ Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio, USA.
⁵⁷ 1] Centre de Recerca en Epidemiologia Ambiental (CREAL), CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain. [2] Hospital del Mar Institute of Medical Research (IMIM), Barcelona, Spain. [3] Department of Nutrition, National School of Public Health, Athens, Greece.
⁵⁸ Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
⁵⁹ Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania.
⁶⁰ Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
⁶¹ Department of Biology, University of Pisa, Pisa, Italy.
⁶² Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii, USA.
⁶³ Oncology Department, ASL1 Massa Carrara, Massa Carrara, Italy.
⁶⁴ Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.
⁶⁵ 1] Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria, Australia. [2] Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia.
⁶⁶ Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
⁶⁷ Alliance Statistics and Data Center, Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA.
⁶⁸ Alliance Statistics and Data Center, Department of Biostatistics and Bioinformatics, Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina, USA.
⁶⁹ 1] Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands. [2] Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
⁷⁰ Department of Epidemiology, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
⁷¹ Pancreas Unit, Department of Digestive Diseases and Internal Medicine, Sant'Orsola-Malpighi Hospital, Bologna, Italy.
⁷² Department of Gastroenterology, Scientific Institute and Regional General Hospital 'Casa Sollievo della Sofferenza', Opera di Padre Pio da Pietrelcina, San Giovanni Rotondo, Italy.
⁷³ 1] Hospital del Mar Institute of Medical Research (IMIM), Barcelona, Spain. [2] Department of Epidemiology, School of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain. [3] CIBERESP, Madrid, Spain.
⁷⁴ 1] Epithelial Carcinogenesis Group, CNIO-Spanish National Cancer Research Centre, Madrid, Spain. [2] Departament de Ciències i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain.
⁷⁵ Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
⁷⁶ ARC-NET: Centre for Applied Research on Cancer, University and Hospital Trust of Verona, Verona, Italy.
⁷⁷ Toxicogenomics Unit, Center for Toxicology and Safety, National Institute of Public Health, Prague, Czech Republic.
⁷⁸ Department of Surgical and Perioperative Sciences, Umeå University, Umeå, Sweden.
⁷⁹ Department of Digestive Tract Diseases, Medical University of Łodz, Łodz, Poland.
⁸⁰ 1st Propaideutic Surgical Department, Hippocration University Hospital, Athens, Greece.
⁸¹ Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark.
⁸² 1] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA. [2] Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece. [3] Hellenic Health Foundation, Athens, Greece.
⁸³ Department of Molecular Biology of Cancer, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
⁸⁴ Department of Social and Preventive Medicine, University at Buffalo, State University of New York, Buffalo, New York, USA.
⁸⁵ Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.
⁸⁶ 1] Department of Environmental Medicine, New York University School of Medicine, New York, New York, USA. [2] New York University Cancer Institute, New York, New York, USA.
⁸⁷ 1] Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. [2].
⁸⁸ 1] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA. [2] Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. [3].
⁸⁹ 1] Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. [2] Cancer Genomics Research Laboratory, National Cancer Institute, Division of Cancer Epidemiology and Genetics, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA. [3].

PMID: 25086665
PMCID: PMC4191666
DOI: 10.1038/ng.3052

Meta-Analysis

Genome-wide association study identifies multiple susceptibility loci for pancreatic cancer

Brian M Wolpin et al. Nat Genet. 2014 Sep.

. 2014 Sep;46(9):994-1000.

doi: 10.1038/ng.3052. Epub 2014 Aug 3.

Authors

Affiliations

¹ 1] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA. [2] Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. [3].
² 1] Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany. [2].
³ 1] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA. [2] Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, USA. [3].
⁴ 1] Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA. [2].
⁵ 1] Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA. [2].
⁶ 1] Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. [2] Cancer Genomics Research Laboratory, National Cancer Institute, Division of Cancer Epidemiology and Genetics, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA.
⁷ 1] Department of Obstetrics and Gynecology, New York University School of Medicine, New York, New York, USA. [2] Department of Environmental Medicine, New York University School of Medicine, New York, New York, USA. [3] New York University Cancer Institute, New York, New York, USA.
⁸ Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
⁹ Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, USA.
¹⁰ 1] Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. [2] Division of Aging, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
¹¹ Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
¹² Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain.
¹³ Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
¹⁴ 1] Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria, Australia. [2] Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia. [3] Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.
¹⁵ Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
¹⁶ Southwest Oncology Group Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
¹⁷ Epidemiology Research Program, American Cancer Society, Atlanta, Georgia, USA.
¹⁸ Group Health Research Institute, Seattle, Washington, USA.
¹⁹ 1] Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. [2] Department of Epidemiology, Bloomberg School of Public Health, Baltimore, Maryland, USA.
²⁰ The Cancer Research Center of Hawaii (retired), Honolulu, Hawaii, USA.
²¹ Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
²² Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
²³ Genetic and Molecular Epidemiology Group, CNIO-Spanish National Cancer Research Centre, Madrid, Spain.
²⁴ Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
²⁵ Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut, USA.
²⁶ 1] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA. [2] Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. [3] Division of Aging, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
²⁷ Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
²⁸ 1] Fred Hutchinson Cancer Research Center, Seattle, Washington, USA. [2] Department of Epidemiology, University of Washington, Seattle, Washington, USA.
²⁹ 1] Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA. [2] Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
³⁰ Department of Epidemiology, University of Washington, Seattle, Washington, USA.
³¹ Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, USA.
³² Department of Laboratory Medicine, University Hospital of Padova, Padua, Italy.
³³ 1] INSERM, Centre for Research in Epidemiology and Population Health (CESP), Nutrition, Hormones and Women's Health Team, Villejuif, France. [2] University Paris Sud, UMRS 1018, Villejuif, France. [3] Institut Gustave Roussy (IGR), Villejuif, France.
³⁴ Westat, Rockville, Maryland, USA.
³⁵ Department of General Surgery, University Hospital Heidelberg, Heidelberg, Germany.
³⁶ 1] National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands. [2] Department of Gastroenterology and Hepatology, University Medical Centre Utrecht, Utrecht, the Netherlands. [3] Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands.
³⁷ Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, Heidelberg University, German Red Cross Blood Service Baden-Württemberg-Hessen, Mannheim, Germany.
³⁸ Division of Cancer Epidemiology, DKFZ, Heidelberg, Germany.
³⁹ Digestive and Liver Disease Unit, 'Sapienza' University of Rome, Rome, Italy.
⁴⁰ 1] Cancer Care Ontario, University of Toronto, Toronto, Ontario, Canada. [2] Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
⁴¹ National Institute for Health Research Liverpool Pancreas Biomedical Research Unit, University of Liverpool, Liverpool, UK.
⁴² Division of Cancer Control and Population Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
⁴³ Department of Surgery, Unit of Experimental Surgical Pathology, University Hospital of Pisa, Pisa, Italy.
⁴⁴ 1] Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. [2] Division of Aging, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. [3] Massachusetts Veteran's Epidemiology, Research and Information Center, Geriatric Research Education and Clinical Center, Veterans Affairs Boston Healthcare System, Boston, Massachusetts, USA.
⁴⁵ 1] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA. [2] Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. [3] Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA.
⁴⁶ 1] Department of Pathology, Sidney Kimmel Cancer Center and Johns Hopkins University, Baltimore, Maryland, USA. [2] Department of Medicine, Sidney Kimmel Cancer Center and Johns Hopkins University, Baltimore, Maryland, USA. [3] Department of Oncology, Sidney Kimmel Cancer Center and Johns Hopkins University, Baltimore, Maryland, USA.
⁴⁷ Laboratory of Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota, USA.
⁴⁸ Preventive Medicine, University of Southern California, Los Angeles, California, USA.
⁴⁹ Prevention and Research Center, Mercy Medical Center, Baltimore, Maryland, USA.
⁵⁰ Cancer Prevention, University of Southern California, Los Angeles, California, USA.
⁵¹ 1] Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. [2] Harvard School of Public Health, Boston, Massachusetts, USA. [3] Harvard Medical School, Boston, Massachusetts, USA.
⁵² The University of North Carolina Eshelman School of Pharmacy, Center for Pharmacogenomics and Individualized Therapy, Lineberger Comprehensive Cancer Center, School of Medicine, Chapel Hill, North Carolina, USA.
⁵³ International Agency for Research on Cancer, Lyon, France.
⁵⁴ Cancer Epidemiology Unit, University of Oxford, Oxford, UK.
⁵⁵ School of Clinical Medicine, University of Cambridge, Cambridge, UK.
⁵⁶ Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio, USA.
⁵⁷ 1] Centre de Recerca en Epidemiologia Ambiental (CREAL), CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain. [2] Hospital del Mar Institute of Medical Research (IMIM), Barcelona, Spain. [3] Department of Nutrition, National School of Public Health, Athens, Greece.
⁵⁸ Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
⁵⁹ Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania.
⁶⁰ Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
⁶¹ Department of Biology, University of Pisa, Pisa, Italy.
⁶² Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii, USA.
⁶³ Oncology Department, ASL1 Massa Carrara, Massa Carrara, Italy.
⁶⁴ Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.
⁶⁵ 1] Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria, Australia. [2] Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia.
⁶⁶ Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
⁶⁷ Alliance Statistics and Data Center, Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA.
⁶⁸ Alliance Statistics and Data Center, Department of Biostatistics and Bioinformatics, Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina, USA.
⁶⁹ 1] Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands. [2] Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
⁷⁰ Department of Epidemiology, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
⁷¹ Pancreas Unit, Department of Digestive Diseases and Internal Medicine, Sant'Orsola-Malpighi Hospital, Bologna, Italy.
⁷² Department of Gastroenterology, Scientific Institute and Regional General Hospital 'Casa Sollievo della Sofferenza', Opera di Padre Pio da Pietrelcina, San Giovanni Rotondo, Italy.
⁷³ 1] Hospital del Mar Institute of Medical Research (IMIM), Barcelona, Spain. [2] Department of Epidemiology, School of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain. [3] CIBERESP, Madrid, Spain.
⁷⁴ 1] Epithelial Carcinogenesis Group, CNIO-Spanish National Cancer Research Centre, Madrid, Spain. [2] Departament de Ciències i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain.
⁷⁵ Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
⁷⁶ ARC-NET: Centre for Applied Research on Cancer, University and Hospital Trust of Verona, Verona, Italy.
⁷⁷ Toxicogenomics Unit, Center for Toxicology and Safety, National Institute of Public Health, Prague, Czech Republic.
⁷⁸ Department of Surgical and Perioperative Sciences, Umeå University, Umeå, Sweden.
⁷⁹ Department of Digestive Tract Diseases, Medical University of Łodz, Łodz, Poland.
⁸⁰ 1st Propaideutic Surgical Department, Hippocration University Hospital, Athens, Greece.
⁸¹ Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark.
⁸² 1] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA. [2] Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece. [3] Hellenic Health Foundation, Athens, Greece.
⁸³ Department of Molecular Biology of Cancer, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
⁸⁴ Department of Social and Preventive Medicine, University at Buffalo, State University of New York, Buffalo, New York, USA.
⁸⁵ Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.
⁸⁶ 1] Department of Environmental Medicine, New York University School of Medicine, New York, New York, USA. [2] New York University Cancer Institute, New York, New York, USA.
⁸⁷ 1] Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. [2].
⁸⁸ 1] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA. [2] Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. [3].
⁸⁹ 1] Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. [2] Cancer Genomics Research Laboratory, National Cancer Institute, Division of Cancer Epidemiology and Genetics, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA. [3].

PMID: 25086665
PMCID: PMC4191666
DOI: 10.1038/ng.3052

Abstract

We performed a multistage genome-wide association study including 7,683 individuals with pancreatic cancer and 14,397 controls of European descent. Four new loci reached genome-wide significance: rs6971499 at 7q32.3 (LINC-PINT, per-allele odds ratio (OR) = 0.79, 95% confidence interval (CI) 0.74-0.84, P = 3.0 × 10(-12)), rs7190458 at 16q23.1 (BCAR1/CTRB1/CTRB2, OR = 1.46, 95% CI 1.30-1.65, P = 1.1 × 10(-10)), rs9581943 at 13q12.2 (PDX1, OR = 1.15, 95% CI 1.10-1.20, P = 2.4 × 10(-9)) and rs16986825 at 22q12.1 (ZNRF3, OR = 1.18, 95% CI 1.12-1.25, P = 1.2 × 10(-8)). We identified an independent signal in exon 2 of TERT at the established region 5p15.33 (rs2736098, OR = 0.80, 95% CI 0.76-0.85, P = 9.8 × 10(-14)). We also identified a locus at 8q24.21 (rs1561927, P = 1.3 × 10(-7)) that approached genome-wide significance located 455 kb telomeric of PVT1. Our study identified multiple new susceptibility alleles for pancreatic cancer that are worthy of follow-up studies.

PubMed Disclaimer

Figures

**Figure 1. Association results, recombination hotspots and LD plots for new pancreatic cancer susceptibility regions (a–e) and one suggestive region (f)**
Top, association results of GWAS data from the stage 1 (gray diamonds), stage 2 (purple diamonds), replication (blue diamonds) and the combined data from stages 1–3 (red diamonds) plotted against −log₁₀ P values (left y axis). Overlaid are likelihood ratio statistics (right y axis) estimating putative recombination hotspots across the region on the basis of five unique sets of 100 randomly selected control samples. Bottom, LD heat map based on r² values from the total control populations for all SNPs included in the GWAS. The data are based on a total number of 7,683 individuals with pancreatic cancer and 14,397 controls of European descent. Shown are results for 5p15.33 (a), 7q32.3 (b), 16q23.1 (c), 13q12.2 (d), 22q12.1 (e), and 8q24.1 (f).

See this image and copyright information in PMC

References

1. Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin. 2014;64:9–29. - PubMed
1. Ferlay J, et al. Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur J Cancer. 2013;49:1374–1403. - PubMed
1. Hidalgo M. Pancreatic cancer. N Engl J Med. 2010;362:1605–1617. - PubMed
1. Klein AP. Genetic susceptibility to pancreatic cancer. Mol Carcinog. 2012;51:14–24. - PMC - PubMed
1. Amundadottir L, et al. Genome-wide association study identifies variants in the ABO locus associated with susceptibility to pancreatic cancer. Nat Genet. 2009;41:986–990. - PMC - PubMed

Publication types

Actions
Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Grants and funding

LinkOut - more resources

Full Text Sources
Other Literature Sources
- scite Smart Citations
Medical
- MedlinePlus Health Information
Molecular Biology Databases
- NIAID Data Ecosystem - Find datasets on Infectious and Immune-mediated Diseases

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Genome-wide association study identifies multiple susceptibility loci for pancreatic cancer

Affiliations

Genome-wide association study identifies multiple susceptibility loci for pancreatic cancer

Authors

Affiliations

Abstract

Figures

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical

Molecular Biology Databases