Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types.
Siddhartha P Kar,
Jonathan Beesley,
Ali Amin Al Olama,
Kyriaki Michailidou,
Jonathan Tyrer,
ZSofia Kote-Jarai,
Kate Lawrenson,
Sara Lindstrom,
Susan J Ramus,
Deborah J Thompson,
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Adam S Kibel,
Agnieszka Dansonka-Mieszkowska,
Agnieszka Michael,
Aida K Dieffenbach,
Aleksandra Gentry-Maharaj,
Alice S Whittemore,
Alicja Wolk,
Alvaro Monteiro,
Ana Peixoto,
Andrzej Kierzek,
Angela Cox,
Anja Rudolph,
Anna Gonzalez-Neira,
Anna H Wu,
Annika Lindblom,
Anthony Swerdlow,
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Argyrios Ziogas,
Arif B Ekici,
Barbara Burwinkel,
Beth Y Karlan,
Børge G Nordestgaard,
Carl Blomqvist,
Catherine Phelan,
Catriona McLean,
Celeste Leigh Pearce,
Celine Vachon,
Cezary Cybulski,
Chavdar Slavov,
Christa Stegmaier,
Christiane Maier,
Christine B Ambrosone,
Claus K Høgdall,
Craig C Teerlink,
Daehee Kang,
Daniel C Tessier,
Daniel J Schaid,
Daniel O Stram,
Daniel W Cramer,
David E Neal,
Diana Eccles,
Dieter Flesch-Janys,
Digna R Velez Edwards,
Dominika Wokozorczyk,
Douglas A Levine,
Drakoulis Yannoukakos,
Elinor J Sawyer,
Elisa V Bandera,
Elizabeth M Poole,
Ellen L Goode,
Elza Khusnutdinova,
Estrid Høgdall,
Fengju Song,
Fiona Bruinsma,
Florian Heitz,
Francesmary Modugno,
Freddie C Hamdy,
Fredrik Wiklund,
Graham G Giles,
Håkan Olsson,
Hans Wildiers,
Hans-Ulrich Ulmer,
Hardev Pandha,
Harvey A Risch,
Hatef Darabi,
Helga B Salvesen,
Heli Nevanlinna,
Henrik Gronberg,
Hermann Brenner,
Hiltrud Brauch,
Hoda Anton-Culver,
Honglin Song,
Hui-Yi Lim,
Iain McNeish,
Ian Campbell,
Ignace Vergote,
Jacek Gronwald,
Jan Lubiński,
Janet L Stanford,
Javier Benítez,
Jennifer A Doherty,
Jennifer B Permuth,
Jenny Chang-Claude,
Jenny L Donovan,
Joe Dennis,
Joellen M Schildkraut,
Johanna Schleutker,
John L Hopper,
Jolanta Kupryjanczyk,
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,
Kathleen Herkommer,
Kay-Tee Khaw,
,
Keitaro Matsuo,
Kenneth Muir,
Kenneth Offitt,
Kexin Chen,
Kirsten B Moysich,
Kristiina Aittomäki,
Kunle Odunsi,
Lambertus A 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,
Matthias W Beckmann,
Matthieu Moisse,
Maureen Sanderson,
Melissa C Southey,
Michael Jones,
Michael Lush,
Michelle A T Hildebrandt,
Ming-Feng Hou,
Minouk J Schoemaker,
Montserrat Garcia-Closas,
Natalia Bogdanova,
Nazneen Rahman,
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Nhu D Le,
Nick Orr,
Nicolas Wentzensen,
Nora Pashayan,
Paolo Peterlongo,
Pascal Guénel,
Paul Brennan,
Paula Paulo,
Penelope M Webb,
Per Broberg,
Peter A Fasching,
Peter Devilee,
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,
Ruth C Travis,
Sara Benlloch,
Sara H Olson,
Shannon K McDonnell,
Shelley S Tworoger,
Sofia Maia,
Sonja Berndt,
Soo Chin Lee,
Soo-Hwang Teo,
Stephen N Thibodeau,
Stig E Bojesen,
Susan M Gapstur,
Susanne Krüger Kjær,
Tanja Pejovic,
Teuvo L J Tammela,
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Thilo Dörk,
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 Zheng,
Weiva Sieh,
William J Blot,
Wojciech Kluzniak,
Xiao-Ou Shu,
Yu-Tang Gao,
Fredrick Schumacher,
Matthew L Freedman,
Andrew Berchuck,
Alison M Dunning,
Jacques Simard,
Christopher A Haiman,
Amanda Spurdle,
Thomas A Sellers,
David J Hunter,
Brian E Henderson,
Peter Kraft,
Stephen J Chanock,
Fergus J Couch,
Per Hall,
Simon A Gayther,
Douglas F Easton,
Georgia Chenevix-Trench,
Rosalind Eeles,
Paul D P Pharoah,
Diether Lambrechts
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.