Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-02-08

AUTHORS

Alison P. Klein, Brian M. Wolpin, Harvey A. Risch, Rachael Z. Stolzenberg-Solomon, Evelina Mocci, Mingfeng Zhang, Federico Canzian, Erica J. Childs, Jason W. Hoskins, Ashley Jermusyk, Jun Zhong, Fei Chen, Demetrius Albanes, Gabriella Andreotti, Alan A. Arslan, Ana Babic, William R. Bamlet, Laura Beane-Freeman, Sonja I. Berndt, Amanda Blackford, Michael Borges, Ayelet Borgida, Paige M. Bracci, Lauren Brais, Paul Brennan, Hermann Brenner, Bas Bueno-de-Mesquita, Julie Buring, Daniele Campa, Gabriele Capurso, Giulia Martina Cavestro, Kari G. Chaffee, Charles C. Chung, Sean Cleary, Michelle Cotterchio, Frederike Dijk, Eric J. Duell, Lenka Foretova, Charles Fuchs, Niccola Funel, Steven Gallinger, J. Michael M. Gaziano, Maria Gazouli, Graham G. Giles, Edward Giovannucci, Michael Goggins, Gary E. Goodman, Phyllis J. Goodman, Thilo Hackert, Christopher Haiman, Patricia Hartge, Manal Hasan, Peter Hegyi, Kathy J. Helzlsouer, Joseph Herman, Ivana Holcatova, Elizabeth A. Holly, Robert Hoover, Rayjean J. Hung, Eric J. Jacobs, Krzysztof Jamroziak, Vladimir Janout, Rudolf Kaaks, Kay-Tee Khaw, Eric A. Klein, Manolis Kogevinas, Charles Kooperberg, Matthew H. Kulke, Juozas Kupcinskas, Robert J. Kurtz, Daniel Laheru, Stefano Landi, Rita T. Lawlor, I.-Min Lee, Loic LeMarchand, Lingeng Lu, Núria Malats, Andrea Mambrini, Satu Mannisto, Roger L. Milne, Beatrice Mohelníková-Duchoňová, Rachel E. Neale, John P. Neoptolemos, Ann L. Oberg, Sara H. Olson, Irene Orlow, Claudio Pasquali, Alpa V. Patel, Ulrike Peters, Raffaele Pezzilli, Miquel Porta, Francisco X. Real, Nathaniel Rothman, Ghislaine Scelo, Howard D. Sesso, Gianluca Severi, Xiao-Ou Shu, Debra Silverman, Jill P. Smith, Pavel Soucek, Malin Sund, Renata Talar-Wojnarowska, Francesca Tavano, Mark D. Thornquist, Geoffrey S. Tobias, Stephen K. Van Den Eeden, Yogesh Vashist, Kala Visvanathan, Pavel Vodicka, Jean Wactawski-Wende, Zhaoming Wang, Nicolas Wentzensen, Emily White, Herbert Yu, Kai Yu, Anne Zeleniuch-Jacquotte, Wei Zheng, Peter Kraft, Donghui Li, Stephen Chanock, Ofure Obazee, Gloria M. Petersen, Laufey T. Amundadottir

ABSTRACT

In 2020, 146,063 deaths due to pancreatic cancer are estimated to occur in Europe and the United States combined. To identify common susceptibility alleles, we performed the largest pancreatic cancer GWAS to date, including 9040 patients and 12,496 controls of European ancestry from the Pancreatic Cancer Cohort Consortium (PanScan) and the Pancreatic Cancer Case-Control Consortium (PanC4). Here, we find significant evidence of a novel association at rs78417682 (7p12/TNS3, P = 4.35 × 10-8). Replication of 10 promising signals in up to 2737 patients and 4752 controls from the PANcreatic Disease ReseArch (PANDoRA) consortium yields new genome-wide significant loci: rs13303010 at 1p36.33 (NOC2L, P = 8.36 × 10-14), rs2941471 at 8q21.11 (HNF4G, P = 6.60 × 10-10), rs4795218 at 17q12 (HNF1B, P = 1.32 × 10-8), and rs1517037 at 18q21.32 (GRP, P = 3.28 × 10-8). rs78417682 is not statistically significantly associated with pancreatic cancer in PANDoRA. Expression quantitative trait locus analysis in three independent pancreatic data sets provides molecular support of NOC2L as a pancreatic cancer susceptibility gene. More... »

PAGES

556

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  • Journal

    TITLE

    Nature Communications

    ISSUE

    1

    VOLUME

    9

    Author Affiliations

  • Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins School of Medicine, Baltimore, MD 21287 USA
  • Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215 USA
  • Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT 06520 USA
  • Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 USA
  • Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD 21231 USA
  • Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 USA
  • Genomic Epidemiology Group, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
  • Department of Environmental Medicine, New York University School of Medicine, New York, NY 10016 USA
  • Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN 55905 USA
  • Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario M5G 1×5 Canada
  • Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA 94158 USA
  • International Agency for Research on Cancer (IARC), 69372 Lyon, France
  • National Center for Tumor Diseases (NCT), 69120 Heidelberg, Germany
  • Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia
  • Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115 USA
  • Department of Biology, University of Pisa, 56126 Pisa, Italy
  • Digestive and Liver Disease Unit, ‘Sapienza’ University of Rome, 00185 Rome, Italy
  • Gastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy
  • Cancer Genomics Research Laboratory, National Cancer Institute, Division of Cancer Epidemiology and Genetics, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702 USA
  • Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario M5T 3M7 Canada
  • Department of Pathology, Academic Medical Center, University of Amsterdam, 1007 MB Amsterdam, The Netherlands
  • Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Bellvitge Biomedical Research Institute (IDIBELL), Catalan Institute of Oncology (ICO), Barcelona, 08908 Spain
  • Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, 65653 Brno, Czech Republic
  • Yale Cancer Center, New Haven, CT 06510 USA
  • Department of Translational Research and The New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy
  • Boston VA Healthcare System, Boston, MA 02132 USA
  • Department of Basic Medical Sciences, Laboratory of Biology, Medical School, National and Kapodistrian University of Athens, 106 79 Athens, Greece
  • Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC 3004 Australia
  • Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109 USA
  • SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA 98109 USA
  • Department of General Surgery, University Hospital Heidelberg, 69120 Heidelberg, Germany
  • Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90032 USA
  • Department of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, TX 77230 USA
  • First Department of Medicine, University of Szeged, 6725 Szeged, Hungary
  • Division of Cancer Control and Population Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 USA
  • Department of Radiation Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD 21231 USA
  • Institute of Public Health and Preventive Medicine, Charles University, 2nd Faculty of Medicine, 150 06 Prague 5, Czech Republic
  • Epidemiology Research Program, American Cancer Society, Atlanta, GA 30303 USA
  • Department of Hematology, Institute of Hematology and Transfusion Medicine, 02-776 Warsaw, Poland
  • Faculty of Medicine, University of Olomouc, 771 47 Olomouc, Czech Republic
  • Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
  • School of Clinical Medicine, University of Cambridge, Cambridge, CB2 0SP UK
  • Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH 44195 USA
  • Universitat Pompeu Fabra (UPF), 08002 Barcelona, Spain
  • Department of Gastroenterology, Lithuanian University of Health Sciences, 44307 Kaunas, Lithuania
  • Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065 USA
  • ARC-NET: Centre for Applied Research on Cancer, University and Hospital Trust of Verona, 37134 Verona, Italy
  • Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115 USA
  • Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI 96813 USA
  • CIBERONC, 28029 Madrid, Spain
  • Oncology Department, ASL1 Massa Carrara, Carrara, 54033 Italy
  • Department of Public Health Solutions, National Institute for Health and Welfare, 00271 Helsinki, Finland
  • Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, VIC 3010 Australia
  • Department of Oncology, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital, 775 20 Olomouc, Czech Republic
  • Population Health Department, QIMR Berghofer Medical Research Institute, Brisbane, 4029 Australia
  • Department of General Surgery, University of Heidelburg, Heidelberg, Germany
  • Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY 10065 USA
  • Department of Surgery, Oncology and Gastroenterology (DiSCOG), University of Padua, 35124 Padua, Italy
  • Pancreas Unit, Department of Digestive Diseases and Internal Medicine, Sant’Orsola-Malpighi Hospital, 40138 Bologna, Italy
  • Hospital del Mar Institute of Medical Research (IMIM), Universitat Autònoma de Barcelona, 08003 Barcelona, Spain
  • Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, 08002 Barcelona, Spain
  • Centre de Recherche en Épidémiologie et Santé des Populations (CESP, Inserm U1018), Facultés de Medicine, Université Paris-Saclay, UPS, UVSQ, Gustave Roussy, 94800 Villejuif, France
  • Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37232 USA
  • Department of Medicine, Georgetown University, Washington, 20057 USA
  • Laboratory for Pharmacogenomics, Biomedical Center, Faculty of Medicine in Pilsen, Charles University, 323 00 Pilsen, Czech Republic
  • Department of Surgical and Perioperative Sciences, Umeå University, 901 85 Umeå, Sweden
  • Department of Digestive Tract Diseases, Medical University of Łodz, 90-647 Łodz, Poland
  • Division of Gastroenterology and Research Laboratory, IRCCS Scientific Institute and Regional General Hospital “Casa Sollievo della Sofferenza”, 71013 San Giovanni Rotondo, FG Italy
  • Division of Research, Kaiser Permanente Northern California, Oakland, CA 94612 USA
  • Department of General, Visceral and Thoracic Surgery, University Hamburg-Eppendorf, 20246 Hamburg, Germany
  • Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205 USA
  • Department of Molecular Biology of Cancer, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, 142 20 Prague 4, Czech Republic
  • Department of Epidemiology and Environmental Health, University at Buffalo, Buffalo, NY 14214 USA
  • Department of Computational Biology, St. Jude Children’s Research Hospital, Memphis, TN 38105 USA
  • Department of Epidemiology, University of Washington, Seattle, WA 98195 USA
  • Perlmutter Cancer Center, New York University School of Medicine, New York, NY 10016 USA
  • Department of Biostatistics, Harvard School of Public Health, Boston, MA 02115 USA
  • Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030 USA
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41467-018-02942-5

    DOI

    http://dx.doi.org/10.1038/s41467-018-02942-5

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1100795973

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/29422604


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