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

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 Zhong, Fei Chen, Demetrius Albanes, Gabriella Andreotti, Alan A. Arslan, Ana Babic, William R. Bamlet, Laura Beane-Freeman, Sonja I. Berndt, Amanda Blackford, Michael Borges, Ayelet Borgida, Paige M. Bracci, Lauren Brais, Paul Brennan, Hermann Brenner, Bas Bueno- de-Mesquita, Julie Buring, Daniele Campa, Gabriele Capurso, Giulia Martina Cavestro, Kari G. Chaffee, Charles C. Chung, Sean Cleary, Michelle Cotterchio, Frederike Dijk, Eric J. Duell, Lenka Foretova, Charles Fuchs, Niccola Funel, Steven Gallinger, J. Michael Gaziano, Maria Gazouli, Graham G. Giles, Edward Giovannucci, Michael Goggins, Gary E. Goodman, Phyllis J. Goodman, Thilo Hackert, Christopher Haiman, Patricia Hartge, Manal Hasan, Peter Hegyi, Kathy J. Helzlsouer, Joseph Herman, Ivana Holcatova, Elizabeth A. Holly, Robert Hoover, Rayjean J. Hung, Eric J. Jacobs, Krzysztof Jamroziak, Vladimir Janout, Rudolf Kaaks, Kay-Tee Khaw, Eric A. Klein, Manolis Kogevinas, Charles Kooperberg, Matthew H. Kulke, Juozas Kupcinskas, Robert J. Kurtz, Daniel Laheru, Stefano Landi, Rita T. Lawlor, I.-Min Lee, Loic LeMarchand, Lingeng Lu, Núria Malats, Andrea Mambrini, Satu Mannisto, Roger L. Milne, Beatrice Mohelníková-Duchoňová, Rachel E. Neale, John P. Neoptolemos, Ann L. Oberg, Sara H. Olson, Irene Orlow, Claudio Pasquali, Alpa V. Patel, Ulrike Peters, Raffaele Pezzilli, Miquel Porta, Francisco X. Real, Nathaniel Rothman, Ghislaine Scelo, Howard D. Sesso, Gianluca Severi, Xiao-Ou Shu, Debra Silverman, Jill P. Smith, Pavel Soucek, Malin Sund, Renata Talar-Wojnarowska, Francesca Tavano, Mark D. Thornquist, Geoffrey S. Tobias, Stephen K. Eeden, Yogesh Vashist, Kala Visvanathan, Pavel Vodicka, Jean Wactawski-Wende, Zhaoming Wang, Nicolas Wentzensen, Emily White, Herbert Yu, Kai Yu, Anne Zeleniuch-Jacquotte, Wei Zheng, Peter Kraft, Donghui Li, Stephen Chanock, Ofure Obazee, Gloria M. Petersen and Laufey T. Amundadottir ()
Additional contact information
Alison P. Klein: 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
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)
Bas Bueno- de-Mesquita: National Institute for Public Health and the Environment (RIVM)
Julie Buring: Brigham and Women’s Hospital
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
Sean Cleary: Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital
Michelle Cotterchio: 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
Maria Gazouli: National and Kapodistrian University of Athens
Graham G. Giles: Cancer Council Victoria
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
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)
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
Loic LeMarchand: University of Hawaii Cancer Center
Lingeng Lu: Yale School of Public Health
Núria Malats: Spanish National Cancer Research Center (CNIO)
Andrea Mambrini: ASL1 Massa Carrara
Satu Mannisto: National Institute for Health and Welfare
Roger L. Milne: Cancer Council Victoria
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)
Francisco X. Real: CIBERONC
Nathaniel Rothman: National Institutes of Health
Ghislaine Scelo: International Agency for Research on Cancer (IARC)
Howard D. Sesso: Brigham and Women’s Hospital
Gianluca Severi: Cancer Council Victoria
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
Herbert Yu: University of Hawaii Cancer Center
Kai Yu: National Institutes of Health
Anne Zeleniuch-Jacquotte: New York University School of Medicine
Wei Zheng: Vanderbilt University School of Medicine
Peter Kraft: Harvard T.H. Chan 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

Nature Communications, 2018, vol. 9, issue 1, 1-11

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.

Date: 2018
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DOI: 10.1038/s41467-018-02942-5

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