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

About this Publication
Title
Genome-wide association study identifies multiple susceptibility loci for pancreatic cancer.
Pubmed ID
25086665 (View this publication on the PubMed website)
Publication
Nat. Genet. 2014 Sep; Volume 46 (Issue 9): Pages 994-1000
Authors
Wolpin BM, Rizzato C, Kraft P, Kooperberg C, Petersen GM, Wang Z, Arslan AA, Beane-Freeman L, Bracci PM, Buring J, Canzian F, Duell EJ, Gallinger S, Giles GG, Goodman GE, Goodman PJ, Jacobs EJ, Kamineni A, Klein AP, Kolonel LN, ...show more Kulke MH, Li D, Malats N, Olson SH, Risch HA, Sesso HD, Visvanathan K, White E, Zheng W, Abnet CC, Albanes D, Andreotti G, Austin MA, Barfield R, Basso D, Berndt SI, Boutron-Ruault MC, Brotzman M, Büchler MW, Bueno-de-Mesquita HB, Bugert P, Burdette L, Campa D, Caporaso NE, Capurso G, Chung C, Cotterchio M, Costello E, Elena J, Funel N, Gaziano JM, Giese NA, Giovannucci EL, Goggins M, Gorman MJ, Gross M, Haiman CA, Hassan M, Helzlsouer KJ, Henderson BE, Holly EA, Hu N, Hunter DJ, Innocenti F, Jenab M, Kaaks R, Key TJ, Khaw KT, Klein EA, Kogevinas M, Krogh V, Kupcinskas J, Kurtz RC, LaCroix A, Landi MT, Landi S, Le Marchand L, Mambrini A, Mannisto S, Milne RL, Nakamura Y, Oberg AL, Owzar K, Patel AV, Peeters PH, Peters U, Pezzilli R, Piepoli A, Porta M, Real FX, Riboli E, Rothman N, Scarpa A, Shu XO, Silverman DT, Soucek P, Sund M, Talar-Wojnarowska R, Taylor PR, Theodoropoulos GE, Thornquist M, Tjønneland A, Tobias GS, Trichopoulos D, Vodicka P, Wactawski-Wende J, Wentzensen N, Wu C, Yu H, Yu K, Zeleniuch-Jacquotte A, Hoover R, Hartge P, Fuchs C, Chanock SJ, Stolzenberg-Solomon RS, Amundadottir LT
Affiliations
  • 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].
  • 1] Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany. [2].
  • 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].
  • 1] Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA. [2].
  • 1] Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA. [2].
  • 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.
  • 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.
  • Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
  • Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, USA.
  • 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.
...show more
  • Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain.
  • Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
  • 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.
  • Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
  • Southwest Oncology Group Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
  • Epidemiology Research Program, American Cancer Society, Atlanta, Georgia, USA.
  • Group Health Research Institute, Seattle, Washington, USA.
  • 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.
  • The Cancer Research Center of Hawaii (retired), Honolulu, Hawaii, USA.
  • Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
  • Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
  • Genetic and Molecular Epidemiology Group, CNIO-Spanish National Cancer Research Centre, Madrid, Spain.
  • Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
  • Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut, USA.
  • 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.
  • Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
  • 1] Fred Hutchinson Cancer Research Center, Seattle, Washington, USA. [2] Department of Epidemiology, University of Washington, Seattle, Washington, USA.
  • 1] Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA. [2] Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
  • Department of Epidemiology, University of Washington, Seattle, Washington, USA.
  • Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, USA.
  • Department of Laboratory Medicine, University Hospital of Padova, Padua, Italy.
  • 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.
  • Westat, Rockville, Maryland, USA.
  • Department of General Surgery, University Hospital Heidelberg, Heidelberg, Germany.
  • 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.
  • Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, Heidelberg University, German Red Cross Blood Service Baden-Württemberg-Hessen, Mannheim, Germany.
  • Division of Cancer Epidemiology, DKFZ, Heidelberg, Germany.
  • Digestive and Liver Disease Unit, 'Sapienza' University of Rome, Rome, Italy.
  • 1] Cancer Care Ontario, University of Toronto, Toronto, Ontario, Canada. [2] Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
  • National Institute for Health Research Liverpool Pancreas Biomedical Research Unit, University of Liverpool, Liverpool, UK.
  • Division of Cancer Control and Population Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
  • Department of Surgery, Unit of Experimental Surgical Pathology, University Hospital of Pisa, Pisa, Italy.
  • 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.
  • 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.
  • 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.
  • Laboratory of Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota, USA.
  • Preventive Medicine, University of Southern California, Los Angeles, California, USA.
  • Prevention and Research Center, Mercy Medical Center, Baltimore, Maryland, USA.
  • Cancer Prevention, University of Southern California, Los Angeles, California, USA.
  • 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.
  • 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.
  • International Agency for Research on Cancer, Lyon, France.
  • Cancer Epidemiology Unit, University of Oxford, Oxford, UK.
  • School of Clinical Medicine, University of Cambridge, Cambridge, UK.
  • Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio, USA.
  • 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.
  • Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
  • Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania.
  • Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
  • Department of Biology, University of Pisa, Pisa, Italy.
  • Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii, USA.
  • Oncology Department, ASL1 Massa Carrara, Massa Carrara, Italy.
  • Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.
  • 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.
  • Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
  • Alliance Statistics and Data Center, Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA.
  • Alliance Statistics and Data Center, Department of Biostatistics and Bioinformatics, Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina, USA.
  • 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.
  • Department of Epidemiology, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
  • Pancreas Unit, Department of Digestive Diseases and Internal Medicine, Sant'Orsola-Malpighi Hospital, Bologna, Italy.
  • Department of Gastroenterology, Scientific Institute and Regional General Hospital 'Casa Sollievo della Sofferenza', Opera di Padre Pio da Pietrelcina, San Giovanni Rotondo, Italy.
  • 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.
  • 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.
  • Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
  • ARC-NET: Centre for Applied Research on Cancer, University and Hospital Trust of Verona, Verona, Italy.
  • Toxicogenomics Unit, Center for Toxicology and Safety, National Institute of Public Health, Prague, Czech Republic.
  • Department of Surgical and Perioperative Sciences, Umeå University, Umeå, Sweden.
  • Department of Digestive Tract Diseases, Medical University of Łodz, Łodz, Poland.
  • 1st Propaideutic Surgical Department, Hippocration University Hospital, Athens, Greece.
  • Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark.
  • 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.
  • Department of Molecular Biology of Cancer, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
  • Department of Social and Preventive Medicine, University at Buffalo, State University of New York, Buffalo, New York, USA.
  • Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.
  • 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.
  • 1] Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. [2].
  • 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].
  • 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].
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.

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