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:
Dr. Jonine Figueroa, PhD
Dr. Jonine Figueroa, PhD
Usher Institute of Population Health Sciences and Informatics
Chancellor's Fellow
Molecular epidemiology
Edinburgh, Scotland | United Kingdom
Dieter Flesch-Janys
Dieter Flesch-Janys
United Kingdom
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 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 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 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 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 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 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

Cancer Discov 2016 09 17;6(9):1052-67. Epub 2016 Jul 17.

VIB Vesalius Research Center, KU Leuven, Leuven, Belgium.

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.

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Source
http://dx.doi.org/10.1158/2159-8290.CD-15-1227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5010513PMC
September 2016
207 Reads
30 Citations
15.930 Impact Factor

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