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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
Kristiina Aittomaki
Ali Amin Al Olama
+278 more
Ali Amin Al Olama
Markus Aly
Markus Aly
Christine B. Ambrosone
Hoda Anton-Culver
Volker Arndt
Volker Arndt
Elisa V. Bandera
Jyotsna Batra
Jyotsna Batra
Matthias W. Beckmann
Jonathan Beesley
Javier Benitez
Sara Benlloch
Sara Benlloch
Andrew Berchuck
Sonja Berndt
Carl Blomqvist
William J. Blot
Natalia Bogdanova
Stig E. Bojesen
Manjeet K. Bolla
Hiltrud Brauch
Paul Brennan
Hermann Brenner
Hermann Brenner
Per Broberg
Fiona Bruinsma
Thomas Bruning
Barbara Burwinkel
Ralf Butzow
Qiuyin Cai
Ian Campbell
Lisa Cannon-Albright
Lisa Cannon-Albright
Jenny Chang-Claude
Stephen J. Chanock
Kexin Chen
Georgia Chenevix-Trench
Judith A. Clements
Linda S. Cook
Fergus J. Couch
Angela Cox
Daniel W. Cramer
Julie M. Cunningham
Cezary Cybulski
Cezary Cybulski
Kamila Czene
Agnieszka Dansonka-Mieszkowska
Hatef Darabi
Joe Dennis
Peter Devilee
Aida K. Dieffenbach
Aida K. Dieffenbach
Jennifer A. Doherty
Jenny L. Donovan
Jenny L. Donovan
Thilo Dork
Alison M. Dunning
Douglas Easton
Douglas F. Easton
Diana Eccles
Todd L. Edwards
A. Eeles
Rosalind Eeles
Arif B. Ekici
Peter A. Fasching
Jonine Figueroa
Liesel M. Fitzgerald
Liesel M. Fitzgerald
Dieter Flesch-Janys
Matthew L. Freedman
Yu Tang Gao
Susan M. Gapstur
Montserrat Garcia-Closas
Simon A. Gayther
Aleksandra Gentry-Maharaj
Graham G. Giles
Graham G. Giles
Anna Gonzalez-Neira
Ellen L. Goode
Marc T. Goodman
Henrik Gronberg
Henrik Gronberg
Jacek Gronwald
Pascal Guenel
Christopher A. Haiman
Christopher A. Haiman
Per Hall
Ute Hamann
Freddie C. Hamdy
Freddie C. Hamdy
Florian Heitz
Brian E. Henderson
Brian E. Henderson
Kathleen Herkommer
Kathleen Herkommer
Michelle A T Hildebrandt
Claus K. Hogdall
Estrid Hogdall
Maartje J. Hooning
Robert N. Hoover
John L. Hopper
Ming Feng Hou
David J. Hunter
Michael Jones
Radka Kaneva
Radka Kaneva
Daehee Kang
Siddhartha P. Kar
Beth Y. Karlan
Tim J. Key
Tim J. Key
Kay Tee Khaw
Kay Tee Khaw
Elza Khusnutdinova
Adam S. Kibel
Adam S. Kibel
Lambertus A. Kiemeney
Andrzej Kierzek
Andrzej Kierzek
Susanne Kruger Kjar
Wojciech Kluzniak
Wojciech Kluzniak
Julia A. Knight
Reidun Kristin Kopperud
Veli Matti Kosma
Z. Sofia Kote-Jarai
Zsofi A. Kote-Jarai
Peter Kraft
Vessela Kristensen
Jolanta Kupryjanczyk
Diether Lambrechts
Kate Lawrenson
Nhu D. Le
Soo Chin Lee
Douglas A. Levine
Qiyuan Li
Hui Yi Lim
Hui Yi Lim
Annika Lindblom
Sara Lindstrom
Karen H. Lu
Jan Lubiński
Manuel Luedeke
Manuel Luedeke
Michael Lush
Robert J. Macinnis
Sofia Maia
Sofia Maia
Christiane Maier
Christiane Maier
Leon F A G Massuger
Keitaro Matsuo
Shannon K. McDonnell
Shannon K. McDonnell
Catriona McLean
Iain McNeish
Usha Menon
Agnieszka Michael
Agnieszka Michael
Kyriaki Michailidou
Roger L. Milne
Vanio Mitev
Vanio Mitev
Francesmary Modugno
Matthieu Moisse
Alvaro Monteiro
Kirsten B. Moysich
Kenneth Muir
Kenneth Muir
David E. Neal
David E. Neal
Roberta Ness
Heli Nevanlinna
Borge G. Nordestgaard
Børge G. Nordestgaard
Kunle Odunsi
Kenneth Offitt
Sara H. Olson
Hakan Olsson
Nick Orr
Hardev Pandha
Hardev Pandha
Jong Y. Park
Jong Y. Park
Nora Pashayan
Nora Pashayan
Paula Paulo
Paula Paulo
Celeste Leigh Pearce
Ana Peixoto
Tanja Pejovic
Jennifer B. Permuth
Paolo Peterlongo
Julian Peto
Paul Pharoah
Paul D P Pharoah
Catherine Phelan
Malcolm C. Pike
Elizabeth M. Poole
Julio Pow-Sang
Nazneen Rahman
Susan J. Ramus
Marjorie Riggan
Harvey A. Risch
Mary Anne Rossing
Anja Rudolph
Helga B. Salvesen
Maureen Sanderson
Elinor J. Sawyer
Daniel J. Schaid
Daniel J. Schaid
Joellen M. Schildkraut
Johanna Schleutker
Johanna Schleutker
Marjanka K. Schmidt
Rita K. Schmutzler
Minouk J. Schoemaker
Fredrick Schumacher
Fredrick Schumacher
Thomas Sellers
Thomas A. Sellers
Veronica Wendy Setiawan
Xiao Ou Shu
Weiva Sieh
Jacques Simard
Chavdar Slavov
Chavdar Slavov
Fengju Song
Honglin Song
Melissa C. Southey
Melissa C. Southey
Amanda Spurdle
Amanda Spurdle
Janet L. Stanford
Janet L. Stanford
Christa Stegmaier
Robert A. Stephenson
Daniel O. Stram
Anthony Swerdlow
Teuvo L J Tammela
Teuvo L J Tammela
Craig C. Teerlink
Manuel R. Teixeira
Manuel R. Teixeira
Soo Hwang Teo
Daniel C. Tessier
Stephen N. Thibodeau
Stephen N. Thibodeau
Deborah J. Thompson
Ruth C. Travis
Ruth C. Travis
Shelley S. Tworoger
Jonathan Tyrer
Hans Ulrich Ulmer
Celine Vachon
Digna R. Velez Edwards
Ignace Vergote
Walther Vogel
Walther Vogel
Tiina Wahlfors
Tiina Wahlfors
Qin Wang
Penelope M. Webb
Nicolas Wentzensen
Alice S. Whittemore
Fredrik Wiklund
Fredrik Wiklund
Hans Wildiers
Robert Winqvist
Dominika Wokozorczyk
Dominika Wokozorczyk
Alicja Wolk
Anna H. Wu
Drakoulis Yannoukakos
Wei Zheng
Argyrios Ziogas
Publication date
1 January 2016
Publisher
Cancer Discov
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Abstract
UNLABELLED: Breast, 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. SIGNIFICANCE: We 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.The Breast Cancer Association Consortium (BCAC), the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL), and the Ovarian Cancer Association Consortium (OCAC) that contributed breast, prostate, and ovarian cancer data analyzed in this study were in part funded by Cancer Research UK [C1287/A10118 and C1287/A12014 for BCAC; C5047/A7357, C1287/A10118, C5047/A3354, C5047/A10692, and C16913/A6135 for PRACTICAL; and C490/A6187, C490/A10119, C490/A10124, C536/A13086, and C536/A6689 for OCAC]. Funding for the Collaborative Oncological Gene-environment Study (COGS) infrastructure came from: the European Community's Seventh Framework Programme under grant agreement number 223175 (HEALTH-F2-2009-223175), Cancer Research UK (C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692, and C8197/A16565), the US National Institutes of Health (CA128978) and the Post-Cancer GWAS Genetic Associations and Mechanisms in Oncology (GAME-ON) initiative (1U19 CA148537, 1U19 CA148065, and 1U19 CA148112), the US Department of Defence (W81XWH-10-1-0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, Komen Foundation for the Cure, the Breast Cancer Research Foundation, and the Ovarian Cancer Research Fund [with donations by the family and friends of Kathryn Sladek Smith (PPD/RPCI.07)]. Additional financial support for contributing studies is documented under Supplementary Financial Support.This is the author accepted manuscript. The final version is available from the American Association for Cancer Research via http://dx.doi.org/10.1158/2159-8290.CD-15-122
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