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Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types.
Authors
ABCTB Investigators
Christine B Ambrosone
+98 more
Ali Amin Al Olama
Hoda Anton-Culver
AOCS Study Group & Australian Cancer Study (Ovarian Cancer)
APCB BioResource
Elisa V Bandera
Jonathan Beesley
Javier Benítez
Carl Blomqvist
Hiltrud Brauch
Hermann Brenner
Fiona Bruinsma
Barbara Burwinkel
Ian Campbell
Jenny Chang-Claude
Angela Cox
Daniel W Cramer
Cezary Cybulski
Agnieszka Dansonka-Mieszkowska
Hatef Darabi
Joe Dennis
Aida K Dieffenbach
Jennifer A Doherty
Jenny L Donovan
Diana Eccles
Digna R Velez Edwards
Arif B Ekici
Dieter Flesch-Janys
Aleksandra Gentry-Maharaj
Graham G Giles
Anna Gonzalez-Neira
Ellen L Goode
Henrik Gronberg
Jacek Gronwald
Freddie C Hamdy
Florian Heitz
John L Hopper
Claus K Høgdall
Estrid Høgdall
Daehee Kang
Siddhartha P Kar
Beth Y Karlan
Elza Khusnutdinova
Adam S Kibel
Andrzej Kierzek
ZSofia Kote-Jarai
Kate Lawrenson
Douglas A Levine
Hui-Yi Lim
Annika Lindblom
Sara Lindstrom
Jan Lubiński
Christiane Maier
Catriona McLean
Iain McNeish
Agnieszka Michael
Kyriaki Michailidou
Francesmary Modugno
Alvaro Monteiro
David E Neal
Heli Nevanlinna
Børge G Nordestgaard
Håkan Olsson
Hardev Pandha
Celeste Leigh Pearce
Ana Peixoto
Jennifer B Permuth
Catherine Phelan
Elizabeth M Poole
Susan J Ramus
Harvey A Risch
Anja Rudolph
Helga B Salvesen
Elinor J Sawyer
Daniel J Schaid
Joellen M Schildkraut
Johanna Schleutker
Chavdar Slavov
Fengju Song
Honglin Song
Janet L Stanford
Christa Stegmaier
Daniel O Stram
Anthony Swerdlow
Craig C Teerlink
Daniel C Tessier
Deborah J Thompson
Jonathan Tyrer
Hans-Ulrich Ulmer
Celine Vachon
Ignace Vergote
Alice S Whittemore
Fredrik Wiklund
Hans Wildiers
Dominika Wokozorczyk
Alicja Wolk
Anna H Wu
Drakoulis Yannoukakos
Argyrios Ziogas
Publication date
1 September 2016
Publisher
eScholarship, University of California
Abstract
UnlabelledBreast, ovarian, and prostate cancers are hormone-related and may have a shared genetic basis, but this has not been investigated systematically by genome-wide association (GWA) studies. Meta-analyses combining the largest GWA meta-analysis data sets for these cancers totaling 112,349 cases and 116,421 controls of European ancestry, all together and in pairs, identified at P < 10(-8) seven new cross-cancer loci: three associated with susceptibility to all three cancers (rs17041869/2q13/BCL2L11; rs7937840/11q12/INCENP; rs1469713/19p13/GATAD2A), two breast and ovarian cancer risk loci (rs200182588/9q31/SMC2; rs8037137/15q26/RCCD1), and two breast and prostate cancer risk loci (rs5013329/1p34/NSUN4; rs9375701/6q23/L3MBTL3). Index variants in five additional regions previously associated with only one cancer also showed clear association with a second cancer type. Cell-type-specific expression quantitative trait locus and enhancer-gene interaction annotations suggested target genes with potential cross-cancer roles at the new loci. Pathway analysis revealed significant enrichment of death receptor signaling genes near loci with P < 10(-5) in the three-cancer meta-analysis.SignificanceWe demonstrate that combining large-scale GWA meta-analysis findings across cancer types can identify completely new risk loci common to breast, ovarian, and prostate cancers. We show that the identification of such cross-cancer risk loci has the potential to shed new light on the shared biology underlying these hormone-related cancers. Cancer Discov; 6(9); 1052-67. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 932
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Last time updated on 25/12/2021