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

Brian M. Wolpin, Cosmeri Rizzato, Peter Kraft, Charles Kooperberg, Gloria M. Petersen, Zhaoming Wang, Alan A. Arslan, Laura Beane-Freeman, Paige M. Bracci, Julie Buring, Federico Canzian, Eric J. Duell, Steven Gallinger, Graham G. Giles, Gary E. Goodman, Phyllis J. Goodman, Eric J. Jacobs, Aruna Kamineni, Alison P. Klein, Laurence N. KolonelMatthew H. Kulke, Donghui Li, Núria Malats, Sara H. Olson, Harvey A. Risch, Howard D. Sesso, Kala Visvanathan, Emily White, Wei Zheng, Christian C. Abnet, Demetrius Albanes, Gabriella Andreotti, Melissa A. Austin, Richard Barfield, Daniela Basso, Sonja I. Berndt, Marie Christine Boutron-Ruault, Michelle Brotzman, Markus W. Büchler, H. Bas Bueno-De-Mesquita, Peter Bugert, Laurie Burdette, Daniele Campa, Neil E. Caporaso, Gabriele Capurso, Charles Chung, Michelle Cotterchio, Eithne Costello, Joanne Elena, Niccola Funel, J. Michael Gaziano, Nathalia A. Giese, Edward L. Giovannucci, Michael Goggins, Megan J. Gorman, Myron Gross, Christopher A. Haiman, Manal Hassan, Kathy J. Helzlsouer, Brian E. Henderson, Elizabeth A. Holly, Nan Hu, David J. Hunter, Federico Innocenti, Mazda Jenab, Rudolf Kaaks, Timothy J. Key, Kay Tee Khaw, Eric A. Klein, Manolis Kogevinas, Vittorio Krogh, Juozas Kupcinskas, Robert C. Kurtz, Andrea Lacroix, Maria T. Landi, Stefano Landi, Loic Le Marchand, Andrea Mambrini, Satu Mannisto, Roger L. Milne, Yusuke Nakamura, Ann L. Oberg, Kouros Owzar, Alpa V. Patel, Petra H M Peeters, Ulrike Peters, Raffaele Pezzilli, Ada Piepoli, Miquel Porta, Francisco X. Real, Elio Riboli, Nathaniel Rothman, Aldo Scarpa, Xiao Ou Shu, Debra T. Silverman, Pavel Soucek, Malin Sund, Renata Talar-Wojnarowska, Philip R. Taylor, George E. Theodoropoulos, Mark Thornquist, Anne Tjønneland, Geoffrey S. Tobias, Dimitrios Trichopoulos, Pavel Vodicka, Jean Wactawski-Wende, Nicolas Wentzensen, Chen Wu, Herbert Yu, Kai Yu, Anne Zeleniuch-Jacquotte, Robert Hoover, Patricia Hartge, Charles Fuchs, Stephen J. Chanock, Rachael S. Stolzenberg-Solomon, Laufey T. Amundadottir

Research output: Contribution to journalArticlepeer-review

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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.

Original languageEnglish (US)
Pages (from-to)994-1000
Number of pages7
JournalNature Genetics
Volume46
Issue number9
DOIs
StatePublished - 2014

Bibliographical note

Funding Information:
This project was funded in whole or in part with federal funds from the National Cancer Institute (NCI), US National Institutes of Health (NIH) under contract number HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the US Department of Health and Human Services, and mention of trade names, commercial products or organizations does not imply endorsement by the US government. Major support for PanScan III sample identification and processing was provided by the Lustgarten Foundation for Pancreatic Cancer Research. Additional support was received from NIH/NCI K07 CA140790, the American Society of Clinical Oncology Conquer Cancer Foundation, the Howard Hughes Medical Institute, the Lustgarten Foundation, the Robert T. and Judith B. Hale Fund for Pancreatic Cancer Research and Promises for Purple to B.M.W. A full list of acknowledgments for each participating study is provided in the Supplementary Note.

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