Common variation at 2p13.3, 3q29, 7p13 and 17q25.1 associated with susceptibility to pancreatic cancer

Erica J. Childs, Evelina Mocci, Daniele Campa, Paige M. Bracci, Steven Gallinger, Michael S Goggins, Donghui Li, Rachel E. Neale, Sara H. Olson, Ghislaine Scelo, Laufey T. Amundadottir, William R. Bamlet, Maarten F. Bijlsma, Amanda Blackford, Michael Borges, Paul Brennan, Hermann Brenner, H. Bas Bueno-De-Mesquita, Federico Canzian, Gabriele CapursoGiulia M. Cavestro, Kari G. Chaffee, Stephen J. Chanock, Sean P. Cleary, Michelle Cotterchio, Lenka Foretova, Charles Fuchs, Niccola Funel, Maria Gazouli, Manal Hassan, Joseph M. Herman, Ivana Holcatova, Elizabeth A. Holly, Robert N. Hoover, Rayjean J. Hung, Vladimir Janout, Timothy J. Key, Juozas Kupcinskas, Robert C. Kurtz, Stefano Landi, Lingeng Lu, Ewa Malecka-Panas, Andrea Mambrini, Beatrice Mohelnikova-Duchonova, John P. Neoptolemos, Ann L. Oberg, Irene Orlow, Claudio Pasquali, Raffaele Pezzilli, Cosmeri Rizzato, Amethyst Saldia, Aldo Scarpa, Rachael Z. Stolzenberg-Solomon, Oliver Strobel, Francesca Tavano, Yogesh K. Vashist, Pavel Vodicka, Brian M. Wolpin, Herbert Yu, Gloria M. Petersen, Harvey A. Risch, Alison Klein

Research output: Contribution to journalArticle

Abstract

Pancreatic cancer is the fourth leading cause of cancer death in the developed world. Both inherited high-penetrance mutations in BRCA2 (ref. 2), ATM, PALB2 (ref. 4), BRCA1 (ref. 5), STK11 (ref. 6), CDKN2A and mismatch-repair genes and low-penetrance loci are associated with increased risk. To identify new risk loci, we performed a genome-wide association study on 9,925 pancreatic cancer cases and 11,569 controls, including 4,164 newly genotyped cases and 3,792 controls in 9 studies from North America, Central Europe and Australia. We identified three newly associated regions: 17q25.1 (LINC00673, rs11655237, odds ratio (OR) = 1.26, 95% confidence interval (CI) = 1.19-1.34, P = 1.42 × 10-14), 7p13 (SUGCT, rs17688601, OR = 0.88, 95% CI = 0.84-0.92, P = 1.41 × 10-8) and 3q29 (TP63, rs9854771, OR = 0.89, 95% CI = 0.85-0.93, P = 2.35 × 10-8). We detected significant association at 2p13.3 (ETAA1, rs1486134, OR = 1.14, 95% CI = 1.09-1.19, P = 3.36 × 10-9), a region with previous suggestive evidence in Han Chinese. We replicated previously reported associations at 9q34.2 (ABO), 13q22.1 (KLF5), 5p15.33 (TERT and CLPTM1), 13q12.2 (PDX1), 1q32.1 (NR5A2), 7q32.3 (LINC-PINT), 16q23.1 (BCAR1) and 22q12.1 (ZNRF3). Our study identifies new loci associated with pancreatic cancer risk.

Original languageEnglish (US)
Pages (from-to)911-916
Number of pages6
JournalNature Genetics
Volume47
Issue number8
DOIs
StatePublished - Aug 30 2015

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ASJC Scopus subject areas

  • Genetics

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Childs, E. J., Mocci, E., Campa, D., Bracci, P. M., Gallinger, S., Goggins, M. S., Li, D., Neale, R. E., Olson, S. H., Scelo, G., Amundadottir, L. T., Bamlet, W. R., Bijlsma, M. F., Blackford, A., Borges, M., Brennan, P., Brenner, H., Bueno-De-Mesquita, H. B., Canzian, F., ... Klein, A. (2015). Common variation at 2p13.3, 3q29, 7p13 and 17q25.1 associated with susceptibility to pancreatic cancer. Nature Genetics, 47(8), 911-916. https://doi.org/10.1038/ng.3341