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 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 Capurso
  • Giulia 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 P Klein

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.

Bibliographical data

Original languageEnglish
ISSN1061-4036
DOIs
Publication statusPublished - 08.2015
PubMed 26098869