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

Author

Listed:
  • Alison P. Klein

    (Johns Hopkins School of Medicine
    Johns Hopkins School of Medicine)

  • Brian M. Wolpin

    (Dana-Farber Cancer Institute)

  • Harvey A. Risch

    (Yale School of Public Health)

  • Rachael Z. Stolzenberg-Solomon

    (National Institutes of Health)

  • Evelina Mocci

    (Johns Hopkins School of Medicine)

  • Mingfeng Zhang

    (National Institutes of Health)

  • Federico Canzian

    (German Cancer Research Center (DKFZ))

  • Erica J. Childs

    (Johns Hopkins School of Medicine)

  • Jason W. Hoskins

    (National Institutes of Health)

  • Ashley Jermusyk

    (National Institutes of Health)

  • Jun Zhong

    (National Institutes of Health)

  • Fei Chen

    (Johns Hopkins School of Medicine)

  • Demetrius Albanes

    (National Institutes of Health)

  • Gabriella Andreotti

    (National Institutes of Health)

  • Alan A. Arslan

    (New York University School of Medicine
    New York University School of Medicine
    New York University School of Medicine)

  • Ana Babic

    (Dana-Farber Cancer Institute)

  • William R. Bamlet

    (Mayo Clinic College of Medicine)

  • Laura Beane-Freeman

    (National Institutes of Health)

  • Sonja I. Berndt

    (National Institutes of Health)

  • Amanda Blackford

    (Johns Hopkins School of Medicine)

  • Michael Borges

    (Johns Hopkins School of Medicine)

  • Ayelet Borgida

    (Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital)

  • Paige M. Bracci

    (University of California, San Francisco)

  • Lauren Brais

    (Dana-Farber Cancer Institute)

  • Paul Brennan

    (International Agency for Research on Cancer (IARC))

  • Hermann Brenner

    (German Cancer Research Center (DKFZ)
    German Cancer Research Center (DKFZ)
    National Center for Tumor Diseases (NCT))

  • Bas Bueno-de-Mesquita

    (National Institute for Public Health and the Environment (RIVM)
    University Medical Centre
    Imperial College London
    University of Malaya)

  • Julie Buring

    (Brigham and Women’s Hospital
    Harvard T.H. Chan School of Public Health)

  • Daniele Campa

    (University of Pisa)

  • Gabriele Capurso

    (‘Sapienza’ University of Rome)

  • Giulia Martina Cavestro

    (IRCCS San Raffaele Scientific Institute)

  • Kari G. Chaffee

    (Mayo Clinic College of Medicine)

  • Charles C. Chung

    (National Institutes of Health
    Frederick National Laboratory for Cancer Research)

  • Sean Cleary

    (Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital)

  • Michelle Cotterchio

    (University of Toronto
    University of Toronto)

  • Frederike Dijk

    (University of Amsterdam)

  • Eric J. Duell

    (Catalan Institute of Oncology (ICO))

  • Lenka Foretova

    (Masaryk Memorial Cancer Institute)

  • Charles Fuchs

    (Yale Cancer Center)

  • Niccola Funel

    (University of Pisa)

  • Steven Gallinger

    (Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital)

  • J. Michael Gaziano

    (Brigham and Women’s Hospital
    Boston VA Healthcare System)

  • Maria Gazouli

    (National and Kapodistrian University of Athens)

  • Graham G. Giles

    (Cancer Council Victoria
    The University of Melbourne
    Monash University)

  • Edward Giovannucci

    (Dana-Farber Cancer Institute)

  • Michael Goggins

    (Johns Hopkins School of Medicine)

  • Gary E. Goodman

    (Fred Hutchinson Cancer Research Center)

  • Phyllis J. Goodman

    (Fred Hutchinson Cancer Research Center)

  • Thilo Hackert

    (University Hospital Heidelberg)

  • Christopher Haiman

    (University of Southern California)

  • Patricia Hartge

    (National Institutes of Health)

  • Manal Hasan

    (University of Texas MD Anderson Cancer Center)

  • Peter Hegyi

    (University of Szeged)

  • Kathy J. Helzlsouer

    (National Institutes of Health)

  • Joseph Herman

    (Johns Hopkins School of Medicine)

  • Ivana Holcatova

    (2nd Faculty of Medicine)

  • Elizabeth A. Holly

    (University of California, San Francisco)

  • Robert Hoover

    (National Institutes of Health)

  • Rayjean J. Hung

    (Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital)

  • Eric J. Jacobs

    (American Cancer Society)

  • Krzysztof Jamroziak

    (Institute of Hematology and Transfusion Medicine)

  • Vladimir Janout

    (University of Ostrava
    University of Olomouc)

  • Rudolf Kaaks

    (German Cancer Research Center (DKFZ))

  • Kay-Tee Khaw

    (University of Cambridge)

  • Eric A. Klein

    (Cleveland Clinic)

  • Manolis Kogevinas

    (Centre for Research in Environmental Epidemiology (CREAL)
    CIBER Epidemiología y Salud Pública (CIBERESP)
    Universitat Autònoma de Barcelona
    Universitat Pompeu Fabra (UPF))

  • Charles Kooperberg

    (Fred Hutchinson Cancer Research Center)

  • Matthew H. Kulke

    (Dana-Farber Cancer Institute)

  • Juozas Kupcinskas

    (Lithuanian University of Health Sciences)

  • Robert J. Kurtz

    (Memorial Sloan Kettering Cancer Center)

  • Daniel Laheru

    (Johns Hopkins School of Medicine)

  • Stefano Landi

    (University of Pisa)

  • Rita T. Lawlor

    (University and Hospital Trust of Verona)

  • I.-Min Lee

    (Brigham and Women’s Hospital
    Harvard School of Public Health)

  • Loic LeMarchand

    (University of Hawaii Cancer Center)

  • Lingeng Lu

    (Yale School of Public Health)

  • Núria Malats

    (Spanish National Cancer Research Center (CNIO)
    CIBERONC)

  • Andrea Mambrini

    (ASL1 Massa Carrara)

  • Satu Mannisto

    (National Institute for Health and Welfare)

  • Roger L. Milne

    (Cancer Council Victoria
    The University of Melbourne)

  • Beatrice Mohelníková-Duchoňová

    (Palacky University Olomouc and University Hospital)

  • Rachel E. Neale

    (QIMR Berghofer Medical Research Institute)

  • John P. Neoptolemos

    (University of Heidelburg)

  • Ann L. Oberg

    (Mayo Clinic College of Medicine)

  • Sara H. Olson

    (Memorial Sloan Kettering Cancer Center)

  • Irene Orlow

    (Memorial Sloan Kettering Cancer Center)

  • Claudio Pasquali

    (University of Padua)

  • Alpa V. Patel

    (American Cancer Society)

  • Ulrike Peters

    (Fred Hutchinson Cancer Research Center)

  • Raffaele Pezzilli

    (Sant’Orsola-Malpighi Hospital)

  • Miquel Porta

    (CIBER Epidemiología y Salud Pública (CIBERESP)
    Universitat Autònoma de Barcelona)

  • Francisco X. Real

    (CIBERONC
    Spanish National Cancer Research Centre-CNIO
    Universitat Pompeu Fabra)

  • Nathaniel Rothman

    (National Institutes of Health)

  • Ghislaine Scelo

    (International Agency for Research on Cancer (IARC))

  • Howard D. Sesso

    (Brigham and Women’s Hospital
    Harvard T.H. Chan School of Public Health)

  • Gianluca Severi

    (Cancer Council Victoria
    The University of Melbourne
    Gustave Roussy)

  • Xiao-Ou Shu

    (Vanderbilt University School of Medicine)

  • Debra Silverman

    (National Institutes of Health)

  • Jill P. Smith

    (Georgetown University)

  • Pavel Soucek

    (Charles University)

  • Malin Sund

    (Umeå University)

  • Renata Talar-Wojnarowska

    (Medical University of Łodz)

  • Francesca Tavano

    (IRCCS Scientific Institute and Regional General Hospital “Casa Sollievo della Sofferenza”)

  • Mark D. Thornquist

    (Fred Hutchinson Cancer Research Center)

  • Geoffrey S. Tobias

    (National Institutes of Health)

  • Stephen K. Eeden

    (Kaiser Permanente Northern California)

  • Yogesh Vashist

    (University Hamburg-Eppendorf)

  • Kala Visvanathan

    (Johns Hopkins Bloomberg School of Public Health)

  • Pavel Vodicka

    (Academy of Sciences of the Czech Republic)

  • Jean Wactawski-Wende

    (University at Buffalo)

  • Zhaoming Wang

    (St. Jude Children’s Research Hospital)

  • Nicolas Wentzensen

    (National Institutes of Health)

  • Emily White

    (Fred Hutchinson Cancer Research Center
    University of Washington)

  • Herbert Yu

    (University of Hawaii Cancer Center)

  • Kai Yu

    (National Institutes of Health)

  • Anne Zeleniuch-Jacquotte

    (New York University School of Medicine
    New York University School of Medicine)

  • Wei Zheng

    (Vanderbilt University School of Medicine)

  • Peter Kraft

    (Harvard T.H. Chan School of Public Health
    Harvard School of Public Health)

  • Donghui Li

    (University of Texas MD Anderson Cancer Center)

  • Stephen Chanock

    (National Institutes of Health)

  • Ofure Obazee

    (German Cancer Research Center (DKFZ))

  • Gloria M. Petersen

    (Mayo Clinic College of Medicine)

  • Laufey T. Amundadottir

    (National Institutes of Health)

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.

Suggested Citation

  • 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 Zh, 2018. "Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer," Nature Communications, Nature, vol. 9(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-02942-5
    DOI: 10.1038/s41467-018-02942-5
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