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 BlackfordMichael 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 M. 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

Research output: Contribution to journalArticleResearch

70 Citations (Scopus)

Abstract

© 2018 The Author(s). 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.
Original languageEnglish
Article number556
JournalNature Communications
Volume9
DOIs
Publication statusPublished - 1 Dec 2018

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