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

Authors :
Childs EJ
Mocci E
Campa D
Bracci PM
Gallinger S
Goggins M
Li D
Neale RE
Olson SH
Scelo G
Amundadottir LT
Bamlet WR
Bijlsma MF
Blackford A
Borges M
Brennan P
Brenner H
Bueno-de-Mesquita HB
Canzian F
Capurso G
Cavestro GM
Chaffee KG
Chanock SJ
Cleary SP
Cotterchio M
Foretova L
Fuchs C
Funel N
Gazouli M
Hassan M
Herman JM
Holcatova I
Holly EA
Hoover RN
Hung RJ
Janout V
Key TJ
Kupcinskas J
Kurtz RC
Landi S
Lu L
Malecka-Panas E
Mambrini A
Mohelnikova-Duchonova B
Neoptolemos JP
Oberg AL
Orlow I
Pasquali C
Pezzilli R
Rizzato C
Saldia A
Scarpa A
Stolzenberg-Solomon RZ
Strobel O
Tavano F
Vashist YK
Vodicka P
Wolpin BM
Yu H
Petersen GM
Risch HA
Klein AP
Source :
Nature genetics [Nat Genet] 2015 Aug; Vol. 47 (8), pp. 911-6. Date of Electronic Publication: 2015 Jun 22.
Publication Year :
2015

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.

Details

Language :
English
ISSN :
1546-1718
Volume :
47
Issue :
8
Database :
MEDLINE
Journal :
Nature genetics
Publication Type :
Academic Journal
Accession number :
26098869
Full Text :
https://doi.org/10.1038/ng.3341