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


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.

SUBMITTER: Childs EJ 

PROVIDER: S-EPMC4520746 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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

Childs Erica J EJ   Mocci Evelina E   Campa Daniele D   Bracci Paige M PM   Gallinger Steven S   Goggins Michael M   Li Donghui D   Neale Rachel E RE   Olson Sara H SH   Scelo Ghislaine G   Amundadottir Laufey T LT   Bamlet William R WR   Bijlsma Maarten F MF   Blackford Amanda A   Borges Michael M   Brennan Paul P   Brenner Hermann H   Bueno-de-Mesquita H Bas HB   Canzian Federico F   Capurso Gabriele G   Cavestro Giulia M GM   Chaffee Kari G KG   Chanock Stephen J SJ   Cleary Sean P SP   Cotterchio Michelle M   Foretova Lenka L   Fuchs Charles C   Funel Niccola N   Gazouli Maria M   Hassan Manal M   Herman Joseph M JM   Holcatova Ivana I   Holly Elizabeth A EA   Hoover Robert N RN   Hung Rayjean J RJ   Janout Vladimir V   Key Timothy J TJ   Kupcinskas Juozas J   Kurtz Robert C RC   Landi Stefano S   Lu Lingeng L   Malecka-Panas Ewa E   Mambrini Andrea A   Mohelnikova-Duchonova Beatrice B   Neoptolemos John P JP   Oberg Ann L AL   Orlow Irene I   Pasquali Claudio C   Pezzilli Raffaele R   Rizzato Cosmeri C   Saldia Amethyst A   Scarpa Aldo A   Stolzenberg-Solomon Rachael Z RZ   Strobel Oliver O   Tavano Francesca F   Vashist Yogesh K YK   Vodicka Pavel P   Wolpin Brian M BM   Yu Herbert H   Petersen Gloria M GM   Risch Harvey A HA   Klein Alison P AP  

Nature genetics 20150622 8


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 A  ...[more]

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