Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types
Abstract
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Aug 31, 2016
- Source ID
- 10.1158/2159-8290.cd-15-1227
Entities
People
- Abctb Investigators
- Adam S. Kibel
- Agnieszka Dansonka-mieszkowska
- Agnieszka Michael
- Aida K. Dieffenbach
- Aleksandra Gentry-Maharaj
- Ali Amin Al Olama
- Alice S. Whittemore
- Alicja Wolk
- Alison Dunning
- Alvaro Monteiro
- Amanda Spurdle
- Ana Peixoto
- Andrew Berchuck
- Andrzej Kierzek
- Angela Cox
- Anja Rudolph
- Anna González-neira
- Anna H. Wu
- Annika Lindblom
- Anthony Swerdlow
- Aocs Study Group & Australian Cancer Study (ovarian Cancer)
- Apcb Bioresource
- Argyrios Ziogas
- Arif B. Ekici
- Barbara Burwinkel
- Beth Karlan
- Brian E. Henderson
- Børge G. Nordestgaard
- Carl Blomqvist
- Catherine Phelan
- Catriona Mclean
- Celeste Leigh Pearce
- Celine M. Vachon
- Cezary Cybulski
- Chavdar Slavov
- Christa Stegmaier
- Christiane Maier
- Christine B. Ambrosone
- Christopher A. Haiman
- Claus K. Høgdall
- Craig C. Teerlink
- Daehee Kang
- Daniel C. Tessier
- Daniel J. Schaid
- Daniel O. Stram
- Daniel W. Cramer
- David E. Neal
- David J. Hunter
- Deborah J. Thompson
- Diana Eccles
- Dieter Flesch-janys
- Diether Lambrechts
- Digna R. Velez Edwards
- Dominika Wokozorczyk
- Douglas A Levine
- Douglas F. Easton
- Drakoulis Yannoukakos
- Elinor J. Sawyer
- Elisa V. Bandera
- Elizabeth M Poole
- Ellen L Goode
- Elza Khusnutdinova
- Estrid Høgdall
- Fengju Song
- Fergus J. Couch
- Fiona Bruinsma
- Florian Heitz
- Francesmary Modugno
- Freddie C. Hamdy
- Fredrick Schumacher
- Fredrik Wiklund
- Georgia Chenevix-Trench
- Graham Giles
- Hans Wildiers
- Hans-ulrich Ulmer
- Hardev Pandha
- Harvey A. Risch
- Hatef Darabi
- Helga B. Salvesen
- Heli Nevanlinna
- Henrik Grönberg
- Hermann Brenner
- Hiltrud Brauch
- Hoda Anton-Culver
- Honglin Song
- Hui-yi Lim
- Håkan Olsson
- Iain A McNeish
- Ian Campbell
- Ignace Vergote
- Jacek Gronwald
- Jacques Simard
- Jan Lubinski
- Janet L. Stanford
- Javier Benitez
- Jennifer A Doherty
- Jennifer B. Permuth
- Jenny Chang-Claude
- Jenny L Donovan
- Joe Dennis
- Joellen M. Schildkraut
- Johanna Schleutker
- John L. Hopper
- Jolanta Kupryjanczyk
- Jonathan Beesley
- Jonathan P Tyrer
- Jong Y Park
- Jonine Figueroa
- Judith A. Clements
- Julia A. Knight
- Julian Peto
- Julie M. Cunningham
- Julio Pow-sang
- Jyotsna Batra
- Kamila Czene
- Karen H. Lu
- Kate Lawrenson
- Kathleen Herkommer
- Kay-tee Khaw
- Kconfab Investigators
- Keitaro Matsuo
- Kenneth Muir
- Kenneth Offitt
- Kexin Chen
- Kirsten B. Moysich
- Kristiina Aittomäki
- Kunle Odunsi
- Kyriaki Michailidou
- Lambertus Kiemeney
- Leon F.a.g. Massuger
- Liesel M. Fitzgerald
- Linda S. Cook
- Lisa Cannon-Albright
- Maartje J. Hooning
- Malcolm C Pike
- Manjeet K. Bolla
- Manuel Luedeke
- Manuel R. Teixeira
- Marc T. Goodman
- Marjanka K Schmidt
- Marjorie Riggan
- Markus Aly
- Mary Anne Rossing
- Matthew L Freedman
- Matthias W. Beckmann
- Matthieu Moisse
- Maureen Sanderson
- Melissa C. Southey
- Michael E Jones
- Michael Lush
- Michelle A.t. Hildebrandt
- Ming-feng Hou
- Minouk J. Schoemaker
- Montserrat García-Closas
- Natalia Bogdanova
- Nazneen Rahman
- Nbcs Investigators
- Nhu D. Le
- Nick Orr
- Nicolas Wentzensen
- Nora Pashayan
- Paolo Peterlongo
- Pascal Guénel
- Paul Brennan
- Paul D.p. Pharoah
- Paula Paulo
- Penelope M. Webb
- Per Broberg
- Per Hall
- Peter A. Fasching
- Peter Devilee
- Peter Kraft
- Qin Wang
- Qiuyin Cai
- Qiyuan Li
- Radka Kaneva
- Ralf Butzow
- Reidun Kristin Kopperud
- Rita K. Schmutzler
- Robert A. Stephenson
- Robert J. Macinnis
- Robert N. Hoover
- Robert Winqvist
- Roberta Ness
- Roger L. Milne
- Rosalind Eeles
- Ruth Travis
- Sara Benlloch
- Sara H. Olson
- Sara Lindström
- Shannon K. Mcdonnell
- Shelley S. Tworoger
- Siddhartha P. Kar
- Simon A Gayther
- Sofia Maia
- Sonja Berndt
- Soo Chin Lee
- Soo-hwang Teo
- Stephen Chanock
- Stephen N. Thibodeau
- Stig E. Bojesen
- Susan J. Ramus
- Susan M. Gapstur
- Susanne Krüger Kjaer
- Tanja Pejovic
- Teuvo L.j. Tammela
- The Genica Network
- The Practical Consortium
- Thilo Dörk
- Thomas A. Sellers
- Thomas Brüning
- Tiina Wahlfors
- Tim J. Key
- Todd L. Edwards
- Usha Menon
- Ute Hamann
- Vanio Mitev
- Veli-matti Kosma
- Veronica Wendy Setiawan
- Vessela Kristensen
- Volker Arndt
- Walther Vogel
- Wei Xing Zheng
- Weiva Sieh
- William J. Blot
- Wojciech Kluzniak
- Xiao-Ou Shu
- Yu-tang Gao
- Zsofia Kote-jarai
Organizations
- Adyar Cancer Institute
- American Cancer Society
- Antoni van Leeuwenhoekziekenhuis
- BC Cancer Agency
- Bashkir State University
- Brigham and Women's Hospital
- Cancer Council Victoria
- Cancer Research UK
- Cedars-Sinai Medical Center
- Copenhagen University Hospital
- Dana–Farber Cancer Institute
- Duke Cancer Institute
- Duke University
- Duke University Hospital
- French National Institute of Health and Medical Research
- Friedrich-Alexander-Universität Erlangen-Nürnberg
- Geisel School of Medicine
- German Cancer Research Center
- H. Lee Moffitt Cancer Center & Research Institute
- Hannover Medical School
- Harvard Medical School
- Harvard T.H. Chan School of Public Health
- Haukeland University Hospital
- Institute of Cancer Research
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- Karolinska Institutet
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- Laval University
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- Oregon Health & Science University
- Oslo University Hospital
- Peter MacCallum Cancer Centre
- Pomeranian Medical University
- Portuguese Oncology Institute
- QIMR Berghofer Medical Research Institute
- Queensland University of Technology
- Radboud University Medical Centre
- Roswell Park Comprehensive Cancer Center
- Ruhr University Bochum
- Rutgers University
- Seoul National University
- Sime Darby Medical Centre
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- Tianjin Medical University
- UZ Leuven
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- United States Department of Defense
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- Universiti Malaya
- University College London
- University Hospital Ulm
- University of Bergen
- University of Bristol
- University of California, Irvine
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- University of Eastern Finland
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- University of Utah
- University of Utah School of Medicine
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- University of Washington
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- Yale School of Public Health