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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.
- Author(s): Kar, Siddhartha P
- Beesley, Jonathan
- Amin Al Olama, Ali
- Michailidou, Kyriaki
- Tyrer, Jonathan
- Kote-Jarai, ZSofia
- Lawrenson, Kate
- Lindstrom, Sara
- Ramus, Susan J
- Thompson, Deborah J
- ABCTB Investigators
- Kibel, Adam S
- Dansonka-Mieszkowska, Agnieszka
- Michael, Agnieszka
- Dieffenbach, Aida K
- Gentry-Maharaj, Aleksandra
- Whittemore, Alice S
- Wolk, Alicja
- Monteiro, Alvaro
- Peixoto, Ana
- Kierzek, Andrzej
- Cox, Angela
- Rudolph, Anja
- Gonzalez-Neira, Anna
- Wu, Anna H
- Lindblom, Annika
- Swerdlow, Anthony
- AOCS Study Group & Australian Cancer Study (Ovarian Cancer)
- APCB BioResource
- Ziogas, Argyrios
- Ekici, Arif B
- Burwinkel, Barbara
- Karlan, Beth Y
- Nordestgaard, Børge G
- Blomqvist, Carl
- Phelan, Catherine
- McLean, Catriona
- Pearce, Celeste Leigh
- Vachon, Celine
- Cybulski, Cezary
- Slavov, Chavdar
- Stegmaier, Christa
- Maier, Christiane
- Ambrosone, Christine B
- Høgdall, Claus K
- Teerlink, Craig C
- Kang, Daehee
- Tessier, Daniel C
- Schaid, Daniel J
- Stram, Daniel O
- Cramer, Daniel W
- Neal, David E
- Eccles, Diana
- Flesch-Janys, Dieter
- Edwards, Digna R Velez
- Wokozorczyk, Dominika
- Levine, Douglas A
- Yannoukakos, Drakoulis
- Sawyer, Elinor J
- Bandera, Elisa V
- Poole, Elizabeth M
- Goode, Ellen L
- Khusnutdinova, Elza
- Høgdall, Estrid
- Song, Fengju
- Bruinsma, Fiona
- Heitz, Florian
- Modugno, Francesmary
- Hamdy, Freddie C
- Wiklund, Fredrik
- Giles, Graham G
- Olsson, Håkan
- Wildiers, Hans
- Ulmer, Hans-Ulrich
- Pandha, Hardev
- Risch, Harvey A
- Darabi, Hatef
- Salvesen, Helga B
- Nevanlinna, Heli
- Gronberg, Henrik
- Brenner, Hermann
- Brauch, Hiltrud
- Anton-Culver, Hoda
- Song, Honglin
- Lim, Hui-Yi
- McNeish, Iain
- Campbell, Ian
- Vergote, Ignace
- Gronwald, Jacek
- Lubiński, Jan
- Stanford, Janet L
- Benítez, Javier
- Doherty, Jennifer A
- Permuth, Jennifer B
- Chang-Claude, Jenny
- Donovan, Jenny L
- Dennis, Joe
- Schildkraut, Joellen M
- Schleutker, Johanna
- Hopper, John L
- Kupryjanczyk, Jolanta
- Park, Jong Y
- Figueroa, Jonine
- Clements, Judith A
- Knight, Julia A
- Peto, Julian
- Cunningham, Julie M
- Pow-Sang, Julio
- Batra, Jyotsna
- Czene, Kamila
- Lu, Karen H
- Herkommer, Kathleen
- Khaw, Kay-Tee
- kConFab Investigators
- Matsuo, Keitaro
- Muir, Kenneth
- Offitt, Kenneth
- Chen, Kexin
- Moysich, Kirsten B
- Aittomäki, Kristiina
- Odunsi, Kunle
- Kiemeney, Lambertus A
- Massuger, Leon FAG
- Fitzgerald, Liesel M
- Cook, Linda S
- Cannon-Albright, Lisa
- Hooning, Maartje J
- Pike, Malcolm C
- Bolla, Manjeet K
- Luedeke, Manuel
- Teixeira, Manuel R
- Goodman, Marc T
- Schmidt, Marjanka K
- Riggan, Marjorie
- Aly, Markus
- Rossing, Mary Anne
- Beckmann, Matthias W
- Moisse, Matthieu
- Sanderson, Maureen
- Southey, Melissa C
- Jones, Michael
- Lush, Michael
- Hildebrandt, Michelle AT
- Hou, Ming-Feng
- Schoemaker, Minouk J
- Garcia-Closas, Montserrat
- Bogdanova, Natalia
- Rahman, Nazneen
- NBCS Investigators
- Le, Nhu D
- Orr, Nick
- Wentzensen, Nicolas
- Pashayan, Nora
- Peterlongo, Paolo
- Guénel, Pascal
- Brennan, Paul
- Paulo, Paula
- Webb, Penelope M
- Broberg, Per
- Fasching, Peter A
- Devilee, Peter
- Wang, Qin
- Cai, Qiuyin
- Li, Qiyuan
- Kaneva, Radka
- Butzow, Ralf
- Kopperud, Reidun Kristin
- Schmutzler, Rita K
- Stephenson, Robert A
- MacInnis, Robert J
- Hoover, Robert N
- Winqvist, Robert
- Ness, Roberta
- Milne, Roger L
- Travis, Ruth C
- Benlloch, Sara
- Olson, Sara H
- McDonnell, Shannon K
- Tworoger, Shelley S
- Maia, Sofia
- Berndt, Sonja
- Lee, Soo Chin
- Teo, Soo-Hwang
- Thibodeau, Stephen N
- Bojesen, Stig E
- Gapstur, Susan M
- Kjær, Susanne Krüger
- Pejovic, Tanja
- Tammela, Teuvo LJ
- GENICA Network
- PRACTICAL consortium
- Dörk, Thilo
- Brüning, Thomas
- Wahlfors, Tiina
- Key, Tim J
- Edwards, Todd L
- Menon, Usha
- Hamann, Ute
- Mitev, Vanio
- Kosma, Veli-Matti
- Setiawan, Veronica Wendy
- Kristensen, Vessela
- Arndt, Volker
- Vogel, Walther
- Zheng, Wei
- Sieh, Weiva
- Blot, William J
- Kluzniak, Wojciech
- Shu, Xiao-Ou
- Gao, Yu-Tang
- Schumacher, Fredrick
- Freedman, Matthew L
- Berchuck, Andrew
- Dunning, Alison M
- Simard, Jacques
- Haiman, Christopher A
- Spurdle, Amanda
- Sellers, Thomas A
- Hunter, David J
- Henderson, Brian E
- Kraft, Peter
- Chanock, Stephen J
- Couch, Fergus J
- Hall, Per
- Gayther, Simon A
- Easton, Douglas F
- Chenevix-Trench, Georgia
- Eeles, Rosalind
- Pharoah, Paul DP
- Lambrechts, Diether
- et al.
Published Web Location
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5010513/No data is associated with this publication.
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.Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.