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.

] Cancer Care Ontario University of Toronto Toronto Ontario Canada [2] Dalla Lana School of Public Health University of Toronto Toronto Ontario Canada

] 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

] 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

] Centre de Recerca en Epidemiologia Ambiental Barcelona Spain [3] Department of Nutrition National School of Public Health Athens Greece

] 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

] 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 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

] Department of Epidemiology Harvard School of Public Health Boston Massachusetts USA [2] Department of Biostatistics Harvard School of Public Health Boston Massachusetts USA [3]

] 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 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]

] 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]

] 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

] Department of Medicine Vanderbilt University Medical Center Nashville Tennessee USA [2] Vanderbilt Ingram Cancer Center Vanderbilt University Medical Center Nashville Tennessee USA

] 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

] Department of Oncology Johns Hopkins University School of Medicine Baltimore Maryland USA [2] Department of Epidemiology Bloomberg School of Public Health Baltimore Maryland USA

] 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

] Division of Cancer Epidemiology and Genetics National Cancer Institute National Institutes of Health Bethesda Maryland USA [2]

] 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

] 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]

] Division of Epidemiology Department of Health Sciences Research Mayo Clinic Rochester Minnesota USA [2]

] 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

] 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

] Division of Public Health Sciences Fred Hutchinson Cancer Research Center Seattle Washington USA [2]

] Epithelial Carcinogenesis Group CNIO Spanish National Cancer Research Centre Madrid Spain [2] Departament de Ciències i de la Salut Universitat Pompeu Fabra Barcelona Spain

] Fred Hutchinson Cancer Research Center Seattle Washington USA [2] Department of Epidemiology University of Washington Seattle Washington USA

] Genomic Epidemiology Group German Cancer Research Center Heidelberg Germany [2]

] Hospital del Mar Institute of Medical Research Barcelona Spain [2] Department of Epidemiology School of Medicine Universitat Autònoma de Barcelona Barcelona Spain [3] CIBERESP Madrid Spain

] INSERM Centre for Research in Epidemiology and Population Health Villejuif France

] 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

] National Institute for Public Health and the Environment 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

1st Propaideutic Surgical Department Hippocration University Hospital Athens Greece

Alliance Statistics and Data Center Department of Biostatistics and Bioinformatics Duke Cancer Institute Duke University Medical Center Durham North Carolina USA

Alliance Statistics and Data Center Division of Biomedical Statistics and Informatics Department of Health Sciences Research Mayo Clinic Rochester Minnesota USA

ARC NET Centre for Applied Research on Cancer University and Hospital Trust of Verona Verona Italy

Cancer Epidemiology Program University of Hawaii Cancer Center Honolulu Hawaii USA

Cancer Epidemiology Unit University of Oxford Oxford UK

Cancer Prevention University of Southern California Los Angeles California USA

Department of Biology University of Pisa Pisa Italy

Department of Biostatistics Harvard School of Public Health Boston Massachusetts USA

Department of Chronic Disease Epidemiology Yale School of Public Health New Haven Connecticut USA

Department of Chronic Disease Prevention National Institute for Health and Welfare Helsinki Finland

Department of Digestive Tract Diseases Medical University of Łodz Łodz Poland

Department of Epidemiology and Biostatistics Memorial Sloan Kettering Cancer Center New York New York USA

Department of Epidemiology and Biostatistics School of Public Health Imperial College London London UK

Department of Epidemiology and Biostatistics University of California San Francisco San Francisco California USA

Department of Epidemiology Fred Hutchinson Cancer Research Center Seattle Washington USA

Department of Epidemiology Harvard School of Public Health Boston Massachusetts USA

Department of Epidemiology Johns Hopkins Bloomberg School of Public Health Baltimore Maryland USA

Department of Epidemiology University of Washington Seattle Washington USA

Department of Gastroenterology Lithuanian University of Health Sciences Kaunas Lithuania

Department of Gastroenterology Scientific Institute and Regional General Hospital 'Casa Sollievo della Sofferenza' Opera di Padre Pio da Pietrelcina San Giovanni Rotondo Italy

Department of Gastrointestinal Medical Oncology University of Texas MD Anderson Cancer Center Houston Texas USA

Department of General Surgery University Hospital Heidelberg Heidelberg Germany

Department of Laboratory Medicine University Hospital of Padova Padua Italy

Department of Medical Oncology Dana Farber Cancer Institute Boston Massachusetts USA

Department of Medicine Memorial Sloan Kettering Cancer Center New York New York USA

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 Surgery Unit of Experimental Surgical Pathology University Hospital of Pisa Pisa Italy

Department of Surgical and Perioperative Sciences Umeå University Umeå Sweden

Digestive and Liver Disease Unit 'Sapienza' University of Rome Rome Italy

Division of Cancer Control and Population Sciences National Cancer Institute National Institutes of Health Bethesda Maryland USA

Division of Cancer Epidemiology and Genetics National Cancer Institute National Institutes of Health Bethesda Maryland USA

Division of Cancer Epidemiology DKFZ Heidelberg Germany

Division of Public Health Sciences Fred Hutchinson Cancer Research Center Seattle Washington USA

Epidemiology and Prevention Unit Fondazione IRCCS Istituto Nazionale dei Tumori Milan Italy

Epidemiology Research Program American Cancer Society Atlanta Georgia USA

Genetic and Molecular Epidemiology Group CNIO Spanish National Cancer Research Centre Madrid Spain

Genomic Epidemiology Group German Cancer Research Center Heidelberg Germany

Glickman Urological and Kidney Institute Cleveland Clinic Cleveland Ohio USA

Group Health Research Institute Seattle Washington USA

Human Genome Center Institute of Medical Science The University of Tokyo Tokyo Japan

Institute of Cancer Epidemiology Danish Cancer Society Copenhagen Denmark

Institute of Transfusion Medicine and Immunology Medical Faculty Mannheim Heidelberg University German Red Cross Blood Service Baden Württemberg Hessen Mannheim Germany

International Agency for Research on Cancer Lyon France

Laboratory of Medicine and Pathology University of Minnesota Minneapolis Minnesota USA

National Institute for Health Research Liverpool Pancreas Biomedical Research Unit University of Liverpool Liverpool UK

Oncology Department ASL1 Massa Carrara Massa Carrara Italy

Pancreas Unit Department of Digestive Diseases and Internal Medicine Sant'Orsola Malpighi Hospital Bologna Italy

Prevention and Research Center Mercy Medical Center Baltimore Maryland USA

Preventive Medicine University of Southern California Los Angeles California USA

Samuel Lunenfeld Research Institute Mount Sinai Hospital Toronto Ontario Canada

School of Clinical Medicine University of Cambridge Cambridge UK

Southwest Oncology Group Statistical Center Fred Hutchinson Cancer Research Center Seattle Washington USA

The Cancer Research Center of Hawaii Honolulu Hawaii 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

Toxicogenomics Unit Center for Toxicology and Safety National Institute of Public Health Prague Czech Republic

Unit of Nutrition Environment and Cancer Cancer Epidemiology Research Program Catalan Institute of Oncology Barcelona Spain

Westat Rockville Maryland USA

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