Identification of six new susceptibility loci for invasive epithelial ovarian cancer.

Authors:
Dr. Sandra Orsulic, Ph.D.
Dr. Sandra Orsulic, Ph.D.
Massachusetts General Hospital
United States
Karoline B Kuchenbaecker Susan J Ramus Jonathan Tyrer Andrew Lee Howard C Shen Jonathan Beesley Kate Lawrenson Lesley McGuffog Sue Healey Janet M Lee Tassja J Spindler Yvonne G Lin Tanja Pejovic Yukie Bean Qiyuan Li Simon Coetzee Dennis Hazelett Alexander Miron Melissa Southey Mary Beth Terry David E Goldgar Saundra S Buys Ramunas Janavicius Cecilia M Dorfling Elizabeth J van Rensburg Susan L Neuhausen Yuan Chun Ding Thomas V O Hansen Lars Jønson Anne-Marie Gerdes Bent Ejlertsen Daniel Barrowdale Joe Dennis Javier Benitez Ana Osorio Maria Jose Garcia Ian Komenaka Jeffrey N Weitzel Pamela Ganschow Paolo Peterlongo Loris Bernard Alessandra Viel Bernardo Bonanni Bernard Peissel Siranoush Manoukian Paolo Radice Laura Papi Laura Ottini Florentia Fostira Irene Konstantopoulou Judy Garber Debra Frost Jo Perkins Radka Platte Steve Ellis Andrew K Godwin Rita Katharina Schmutzler Alfons Meindl Christoph Engel Christian Sutter Olga M Sinilnikova Francesca Damiola Sylvie Mazoyer Dominique Stoppa-Lyonnet Kathleen Claes Kim De Leeneer Judy Kirk Gustavo C Rodriguez Marion Piedmonte David M O'Malley Miguel de la Hoya Trinidad Caldes Kristiina Aittomäki Heli Nevanlinna J Margriet Collée Matti A Rookus Jan C Oosterwijk Laima Tihomirova Nadine Tung Ute Hamann Claudine Isaccs Marc Tischkowitz Evgeny N Imyanitov Maria A Caligo Ian G Campbell Frans B L Hogervorst Edith Olah Orland Diez Ignacio Blanco Joan Brunet Conxi Lazaro Miquel Angel Pujana Anna Jakubowska Jacek Gronwald Jan Lubinski Grzegorz Sukiennicki Rosa B Barkardottir Marie Plante Jacques Simard Penny Soucy Marco Montagna Silvia Tognazzo Manuel R Teixeira Vernon S Pankratz Xianshu Wang Noralane Lindor Csilla I Szabo Noah Kauff Joseph Vijai Carol A Aghajanian Georg Pfeiler Andreas Berger Christian F Singer Muy-Kheng Tea Catherine M Phelan Mark H Greene Phuong L Mai Gad Rennert Anna Marie Mulligan Sandrine Tchatchou Irene L Andrulis Gord Glendon Amanda Ewart Toland Uffe Birk Jensen Torben A Kruse Mads Thomassen Anders Bojesen Jamal Zidan Eitan Friedman Yael Laitman Maria Soller Annelie Liljegren Brita Arver Zakaria Einbeigi Marie Stenmark-Askmalm Olufunmilayo I Olopade Robert L Nussbaum Timothy R Rebbeck Katherine L Nathanson Susan M Domchek Karen H Lu Beth Y Karlan Christine Walsh Jenny Lester Alexander Hein Arif B Ekici Matthias W Beckmann Peter A Fasching Diether Lambrechts Els Van Nieuwenhuysen Ignace Vergote Sandrina Lambrechts Ed Dicks Jennifer A Doherty Kristine G Wicklund Mary Anne Rossing Anja Rudolph Jenny Chang-Claude Shan Wang-Gohrke Ursula Eilber Kirsten B Moysich Kunle Odunsi Lara Sucheston Shashi Lele Lynne R Wilkens Marc T Goodman Pamela J Thompson Yurii B Shvetsov Ingo B Runnebaum Matthias Dürst Peter Hillemanns Thilo Dörk Natalia Antonenkova Natalia Bogdanova Arto Leminen Liisa M Pelttari Ralf Butzow Francesmary Modugno Joseph L Kelley Robert P Edwards Roberta B Ness Andreas du Bois Florian Heitz Ira Schwaab Philipp Harter Keitaro Matsuo Satoyo Hosono Allan Jensen Susanne Kruger Kjaer Estrid Hogdall Hanis Nazihah Hasmad Mat Adenan Noor Azmi Soo-Hwang Teo Yin-Ling Woo Brooke L Fridley Ellen L Goode Julie M Cunningham Robert A Vierkant Fiona Bruinsma Graham G Giles Dong Liang Michelle A T Hildebrandt Xifeng Wu Douglas A Levine Maria Bisogna Andrew Berchuck Edwin S Iversen Joellen M Schildkraut Patrick Concannon Rachel Palmieri Weber Daniel W Cramer Kathryn L Terry Elizabeth M Poole Shelley S Tworoger Elisa V Bandera Irene Orlow Sara H Olson Camilla Krakstad Helga B Salvesen Ingvild L Tangen Line Bjorge Anne M van Altena Katja K H Aben Lambertus A Kiemeney Leon F A G Massuger Melissa Kellar Angela Brooks-Wilson Linda E Kelemen Linda S Cook Nhu D Le Cezary Cybulski Hannah Yang Jolanta Lissowska Louise A Brinton Nicolas Wentzensen Claus Hogdall Lene Lundvall Lotte Nedergaard Helen Baker Honglin Song Diana Eccles Ian McNeish James Paul Karen Carty Nadeem Siddiqui Rosalind Glasspool Alice S Whittemore Joseph H Rothstein Valerie McGuire Weiva Sieh Bu-Tian Ji Wei Zheng Xiao-Ou Shu Yu-Tang Gao Barry Rosen Harvey A Risch John R McLaughlin Steven A Narod Alvaro N Monteiro Ann Chen Hui-Yi Lin Jenny Permuth-Wey Thomas A Sellers Ya-Yu Tsai Zhihua Chen Argyrios Ziogas Hoda Anton-Culver Aleksandra Gentry-Maharaj Usha Menon Patricia Harrington Alice W Lee Anna H Wu Celeste L Pearce Gerry Coetzee Malcolm C Pike Agnieszka Dansonka-Mieszkowska Agnieszka Timorek Iwona K Rzepecka Jolanta Kupryjanczyk Matt Freedman Houtan Noushmehr Douglas F Easton Kenneth Offit Fergus J Couch Simon Gayther Paul P Pharoah Antonis C Antoniou Georgia Chenevix-Trench

Nat Genet 2015 Feb 12;47(2):164-71. Epub 2015 Jan 12.

Cancer Division, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.

Genome-wide association studies (GWAS) have identified 12 epithelial ovarian cancer (EOC) susceptibility alleles. The pattern of association at these loci is consistent in BRCA1 and BRCA2 mutation carriers who are at high risk of EOC. After imputation to 1000 Genomes Project data, we assessed associations of 11 million genetic variants with EOC risk from 15,437 cases unselected for family history and 30,845 controls and from 15,252 BRCA1 mutation carriers and 8,211 BRCA2 mutation carriers (3,096 with ovarian cancer), and we combined the results in a meta-analysis. This new study design yielded increased statistical power, leading to the discovery of six new EOC susceptibility loci. Variants at 1p36 (nearest gene, WNT4), 4q26 (SYNPO2), 9q34.2 (ABO) and 17q11.2 (ATAD5) were associated with EOC risk, and at 1p34.3 (RSPO1) and 6p22.1 (GPX6) variants were specifically associated with the serous EOC subtype, all with P < 5 × 10(-8). Incorporating these variants into risk assessment tools will improve clinical risk predictions for BRCA1 and BRCA2 mutation carriers.

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