Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer
Alison P. Klein(Johns Hopkins University), Brian M. Wolpin(Dana-Farber Cancer Institute), Harvey A. Risch(Yale University), Rachael Z. Stolzenberg‐Solomon(National Institutes of Health), Evelina Mocci(Johns Hopkins University), Mingfeng Zhang(National Institutes of Health), Federico Canzian(German Cancer Research Center), Erica J. Childs(Johns Hopkins University), Jason W. Hoskins(National Institutes of Health), Ashley Jermusyk(National Institutes of Health), Jun Zhong(National Institutes of Health), Fei Chen(Johns Hopkins University), Demetrius Albanes(National Institutes of Health), Gabriella Andreotti(National Institutes of Health), Alan A. Arslan(New York University), Ana Babić(Dana-Farber Cancer Institute), William R. Bamlet(Mayo Clinic), Laura E. Beane Freeman(National Institutes of Health), Sonja I. Berndt(National Institutes of Health), Amanda L. Blackford(Johns Hopkins University), Michael Borges(Johns Hopkins University), Ayelet Borgida(Mount Sinai Hospital), Paige M. Bracci(University of California, San Francisco), Lauren K. Brais(Dana-Farber Cancer Institute), Paul Brennan(Centre international de recherche sur le cancer), Hermann Brenner(German Cancer Research Center), Bas Bueno‐de‐Mesquita(University Medical Center Utrecht), Julie E. Buring(Brigham and Women's Hospital), Daniele Campa(University of Pisa), Gabriele Capurso(Sapienza University of Rome), Giulia Martina Cavestro(Vita-Salute San Raffaele University), Kari G. Chaffee(Mayo Clinic), Charles C. Chung(Leidos (United States)), Sean P. Cleary(Mount Sinai Hospital), Michelle Cotterchio(University of Toronto), Frederike Dijk(Amsterdam UMC Location University of Amsterdam), Eric J. Duell(Institut d'Investigació Biomédica de Bellvitge), Lenka Foretová(Masaryk Memorial Cancer Institute), Charles S. Fuchs(Yale Cancer Center), Niccola Funel(University of Pisa), Steven Gallinger(Mount Sinai Hospital), J. Michael Gaziano(Brigham and Women's Hospital), Maria Gazouli(National and Kapodistrian University of Athens), Graham G. Giles(The University of Melbourne), Edward Giovannucci(Dana-Farber Cancer Institute), Michael Goggins(Johns Hopkins University), Gary E. Goodman(Fred Hutch Cancer Center), Phyllis J. Goodman(Fred Hutch Cancer Center), Thilo Hackert(Heidelberg University), Christopher A. Haiman(University of Southern California), Patricia Hartge(National Institutes of Health), Manal Hasan(The University of Texas MD Anderson Cancer Center), Péter Hegyi(University of Szeged), Kathy J. Helzlsouer(National Institutes of Health), Joseph M. Herman(Johns Hopkins University), Ivana Holcátová(Charles University), Elizabeth A. Holly(University of California, San Francisco), Robert N. Hoover(National Institutes of Health), Rayjean J. Hung(Mount Sinai Hospital), Eric J. Jacobs(American Cancer Society), Krzysztof Jamroziak(Instytut Hematologii i Transfuzjologi), Vladimír Janout(University of Ostrava), Rudolf Kaaks(German Cancer Research Center), Kay‐Tee Khaw(University of Cambridge), Eric A. Klein(Cleveland Clinic), Manolis Kogevinas(Universitat Autònoma de Barcelona), Charles Kooperberg(Fred Hutch Cancer Center), Matthew H. Kulke(Dana-Farber Cancer Institute), Juozas Kupčinskas(Lithuanian University of Health Sciences), Robert J. Kurtz(Memorial Sloan Kettering Cancer Center), Daniel A. Laheru(Johns Hopkins University), Stefano Landi(University of Pisa), Rita T. Lawlor(University of Verona), I.-Min Lee(Brigham and Women's Hospital), Loı̈c Le Marchand(University of Hawaiʻi at Mānoa), Lingeng Lu(Yale University), Núria Malats(Spanish National Cancer Research Centre), Andrea Mambrini(Accademia di Belle Arti di Carrara), Satu Männistö(Finnish Institute for Health and Welfare), Roger L. Milne(The University of Melbourne), Beatrice Mohelníková-Duchoňová(University Hospital Olomouc), Rachel Ε. Neale(QIMR Berghofer Medical Research Institute), John P. Neoptolemos(Heidelberg University), Ann L. Oberg(Mayo Clinic), 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 Hutch Cancer Center), Raffaele Pezzilli(IRCCS Azienda Ospedliero-Universitaria di Bologna Policlinico di Sant'Orsola), Miquel Porta(Universitat Autònoma de Barcelona), Francisco X. Real(Universitat Pompeu Fabra), Nathaniel Rothman(National Institutes of Health), Ghislaine Scélo(Centre international de recherche sur le cancer), Howard D. Sesso(Brigham and Women's Hospital), Gianluca Severi(Inserm), Xiao‐Ou Shu(Vanderbilt University), Debra T. Silverman(National Institutes of Health), Jill P. Smith(Georgetown University), Pavel Souček(Charles University), Malin Sund(Umeå University), Renata Talar‐Wojnarowska(Medical University of Lodz), Francesca Tavano(Casa Sollievo della Sofferenza), Mark Thornquist(Fred Hutch Cancer Center), Geoffrey S. Tobias(National Institutes of Health), Stephen K. Van Den Eeden(Kaiser Permanente), Yogesh K. Vashist(Universität Hamburg), Kala Visvanathan(Johns Hopkins University), Pavel Vodička(Czech Academy of Sciences), Jean Wactawski‐Wende(University at Buffalo, State University of New York), Zhaoming Wang(St. Jude Children's Research Hospital), Nicolas Wentzensen(National Institutes of Health), Emily White(University of Washington), Herbert Yu(University of Hawaiʻi at Mānoa), Kai Yu(National Institutes of Health), Anne Zeleniuch‐Jacquotte(New York University), Wei Zheng(Vanderbilt University), Peter Kraft(Harvard University), Donghui Li(The University of Texas MD Anderson Cancer Center), Stephen J. Chanock(National Institutes of Health), Ofure Obazee(German Cancer Research Center), Gloria M. Petersen(Mayo Clinic), Laufey T. Ámundadóttir(National Institutes of Health)
Cited by 278Open Access
Abstract
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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