Common variation at 2p13.3, 3q29, 7p13 and 17q25.1 associated with susceptibility to pancreatic cancer
Childs, Erica J; Mocci, Evelina; Campa, Daniele; Bracci, Paige M; Gallinger, Steven; Goggins, Michael; Li, Donghui; Neale, Rachel E; Olson, Sara H; Scelo, Ghislaine; Amundadottir, Laufey T; Bamlet, William R.; Bijlsma, Maarten F; Blackford, Amanda; Borges, Michael; Brennan, Paul; Brenner, Hermann; Bueno-De-Mesquita, H. Bas; Canzian, Federico; Capurso, Gabriele; Cavestro, Giulia Martina; Chaffee, Kari G.; Chanock, Stephen J.; Cleary, Sean P.; Cotterchio, Michelle; Foretova, Lenka; Fuchs, Charles; Funel, Niccola; Gazouli, Maria; Hassan, Manal; Herman, Joseph M.; Holcatova, Ivana; Holly, Elizabeth A; Hoover, Robert N.; Hung, Rayjean J.; Janout, Vladimir; Key, Timothy J.; Kupcinskas, Juozas; Kurtz, Robert C; Landi, Stefano; Lu, Lingeng; Malecka-Panas, Ewa; Mambrini, Andrea; Mohelnikova-Duchonova, Beatrice; Neoptolemos, John P.; Oberg, Ann L; Orlow, Irene; Pasquali, Claudio; Pezzilli, Raffaele; Rizzato, Cosmeri; Saldia, Amethyst; Scarpa, Aldo; Stolzenberg-Solomon, Rachael Z.; Strobel, Oliver; Tavano, Francesca; Vashist, Yogesh K.; Vodicka, Pavel; Wolpin, Brian M; Yu, Herbert; Petersen, Gloria M; Risch, Harvey A.; Klein, Alison P
(2015) Nature Genetics, volume 47, issue 8, pp. 911 - 916
(Article)
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
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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.
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Keywords: Genetics
ISSN: 1061-4036
Publisher: Nature Publishing Group
(Peer reviewed)