TY - JOUR
T1 - Common variation at 2p13.3, 3q29, 7p13 and 17q25.1 associated with susceptibility to pancreatic cancer
AU - Childs, Erica J.
AU - Mocci, Evelina
AU - Campa, Daniele
AU - Bracci, Paige M.
AU - Gallinger, Steven
AU - Goggins, Michael
AU - Li, Donghui
AU - Neale, Rachel E.
AU - Olson, Sara H.
AU - Scelo, Ghislaine
AU - Amundadottir, Laufey T.
AU - Bamlet, William R.
AU - Bijlsma, Maarten F.
AU - Blackford, Amanda
AU - Borges, Michael
AU - Brennan, Paul
AU - Brenner, Hermann
AU - Bueno-De-Mesquita, H. Bas
AU - Canzian, Federico
AU - Capurso, Gabriele
AU - Cavestro, Giulia M.
AU - Chaffee, Kari G.
AU - Chanock, Stephen J.
AU - Cleary, Sean P.
AU - Cotterchio, Michelle
AU - Foretova, Lenka
AU - Fuchs, Charles
AU - Funel, Niccola
AU - Gazouli, Maria
AU - Hassan, Manal
AU - Herman, Joseph M.
AU - Holcatova, Ivana
AU - Holly, Elizabeth A.
AU - Hoover, Robert N.
AU - Hung, Rayjean J.
AU - Janout, Vladimir
AU - Key, Timothy J.
AU - Kupcinskas, Juozas
AU - Kurtz, Robert C.
AU - Landi, Stefano
AU - Lu, Lingeng
AU - Malecka-Panas, Ewa
AU - Mambrini, Andrea
AU - Mohelnikova-Duchonova, Beatrice
AU - Neoptolemos, John P.
AU - Oberg, Ann L.
AU - Orlow, Irene
AU - Pasquali, Claudio
AU - Pezzilli, Raffaele
AU - Rizzato, Cosmeri
AU - Saldia, Amethyst
AU - Scarpa, Aldo
AU - Stolzenberg-Solomon, Rachael Z.
AU - Strobel, Oliver
AU - Tavano, Francesca
AU - Vashist, Yogesh K.
AU - Vodicka, Pavel
AU - Wolpin, Brian M.
AU - Yu, Herbert
AU - Petersen, Gloria M.
AU - Risch, Harvey A.
AU - Klein, Alison P.
N1 - Publisher Copyright:
© 2015 Nature America, Inc. All rights reserved.
PY - 2015/8/30
Y1 - 2015/8/30
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84938289037&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84938289037&partnerID=8YFLogxK
U2 - 10.1038/ng.3341
DO - 10.1038/ng.3341
M3 - Article
C2 - 26098869
AN - SCOPUS:84938289037
SN - 1061-4036
VL - 47
SP - 911
EP - 916
JO - Nature genetics
JF - Nature genetics
IS - 8
ER -