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Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer.

About this Publication
Title
Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer.
Pubmed ID
29422604 (View this publication on the PubMed website)
Digital Object Identifier
Publication
Nat Commun. 2018 Feb 8; Volume 9 (Issue 1): Pages 556
Authors
Klein AP, Wolpin BM, Risch HA, Stolzenberg-Solomon RZ, Mocci E, Zhang M, Canzian F, Childs EJ, Hoskins JW, Jermusyk A, Zhong J, Chen F, Albanes D, Andreotti G, Arslan AA, Babic A, Bamlet WR, Beane-Freeman L, Berndt SI, Blackford A, ...show more Borges M, Borgida A, Bracci PM, Brais L, Brennan P, Brenner H, Bueno-de-Mesquita B, Buring J, Campa D, Capurso G, Cavestro GM, Chaffee KG, Chung CC, Cleary S, Cotterchio M, Dijk F, Duell EJ, Foretova L, Fuchs C, Funel N, Gallinger S, M Gaziano JM, Gazouli M, Giles GG, Giovannucci E, Goggins M, Goodman GE, Goodman PJ, Hackert T, Haiman C, Hartge P, Hasan M, Hegyi P, Helzlsouer KJ, Herman J, Holcatova I, Holly EA, Hoover R, Hung RJ, Jacobs EJ, Jamroziak K, Janout V, Kaaks R, Khaw KT, Klein EA, Kogevinas M, Kooperberg C, Kulke MH, Kupcinskas J, Kurtz RJ, Laheru D, Landi S, Lawlor RT, Lee IM, LeMarchand L, Lu L, Malats N, Mambrini A, Mannisto S, Milne RL, Mohelníková-Duchoňová B, Neale RE, Neoptolemos JP, Oberg AL, Olson SH, Orlow I, Pasquali C, Patel AV, Peters U, Pezzilli R, Porta M, Real FX, Rothman N, Scelo G, Sesso HD, Severi G, Shu XO, Silverman D, Smith JP, Soucek P, Sund M, Talar-Wojnarowska R, Tavano F, Thornquist MD, Tobias GS, Van Den Eeden SK, Vashist Y, Visvanathan K, Vodicka P, Wactawski-Wende J, Wang Z, Wentzensen N, White E, Yu H, Yu K, Zeleniuch-Jacquotte A, Zheng W, Kraft P, Li D, Chanock S, Obazee O, Petersen GM, Amundadottir LT
Affiliations
  • Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, 21231, USA. aklein1@jhmi.edu.
  • 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 Obstetrics and Gynecology, 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.
  • Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins School of Medicine, Baltimore, MD, 21287, USA.
...show more
  • 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.
  • Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.
  • Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), 3720 BA, Bilthoven, The Netherlands.
  • Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, 02215, 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 Care Ontario, University of Toronto, Toronto, Ontario, M5G 2L7, 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.
  • Division of Aging, Brigham and Women's Hospital, Boston, MA, 02115, USA.
  • Department of Basic Medical Sciences, Laboratory of Biology, Medical School, National and Kapodistrian University of Athens, 106 79, Athens, Greece.
  • Cancer Epidemiology and Intelligence Division, Cancer Council Victoria, 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.
  • Department of Epidemiology and Public Health, Faculty of Medicine, University of Ostrava, 701 03, Ostrava, 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.
  • ISGlobal, Centre for Research in Environmental Epidemiology (CREAL), 08003, 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.
  • Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, 96813, USA.
  • Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Center (CNIO), 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.
  • 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.
  • CIBER Epidemiología y Salud Pública (CIBERESP), 08003, Barcelona, Spain.
  • CIBERONC, 28029, Madrid, Spain.
  • 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 Population Health, New York University School of Medicine, New York, NY, 10016, USA.
  • Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, 02115, USA.
  • Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
  • Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA. amundadottirl@mail.nih.gov.
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.

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