Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer

Catherine M. Phelan , Karoline B. Kuchenbaecker , Jonathan Tyrer , Siddhartha Kar , Kate Lawrenson , Stacey J. Winham , Joe Dennis , Ailith Pirie , Marjorie Riggan , Ganna Chornokur , Madalene A. Earp , Paulo C. Lyra Jr. , Janet M. Lee , Simon Coetzee , Jonathan Beesley , Lesley Mc Guffog , Penny Soucy , Ed Dicks , Andrew Lee , Daniel Barrowdale , Julie Lecarpentier , Goska Leslie , Cora M. Aalfs , Katja Aben , Marcia Adams , Julian Adlard , Irene L. Andrulis , Hoda Anton-Culver , Natalia Antonenkova , Aocs Study Group , Gerasimos Aravantinos , Norbert Arnold , Banu K. Arun , Brita Arver , Jacopo Azzollini , Judith Balmaña , Susana Banerjee , Laure Barjhoux (1) , Rosa Barkardottir , Yukie Bean , Matthias Beckmann , Alicia Beeghly-Fadiel , Javier Benitez , Marina Bermisheva , Marcus Bernardini , Michael Birrer , Line Bjorge , Amanda Black , Kenneth Blankstein , Marinus Blok , Clara Bodelon , Natalia Bogdanova , Anders Bojesen , Bernardo Bonanni , Åke Borg , Angela Bradbury , James Brenton , Carole Brewer , Louise Brinton , Per Broberg , Angela Brooks-Wilson , Fiona Bruinsma , Joan Brunet , Bruno Buecher (2) , Ralf Butzow , Saundra Buys , Trinidad Caldes , Maria A. Caligo , Ian Campbell , Rikki Cannioto , Michael E. Carney , Terence Cescon , Salina Chan , Jenny Chang-Claude , Stephen Chanock , Xiao Qing Chen , Yoke-Eng Chiew , Jocelyne Chiquette , Wendy Chung , Kathleen Claes , Thomas Conner , Linda Cook , Jackie Cook , Daniel Cramer , Julie Cunningham , Aimee d'Aloisio , Mary B. Daly , Francesca Damiola (1) , Sakaeva Dina Damirovna , Agnieszka Dansonka-Mieszkowska , Fanny Dao , Rosemarie Davidson , Anna Defazio , Capucine Delnatte (3) , Kimberly Doheny , Orland Diez , Yuan Chun Ding , Jennifer Anne Doherty , Susan M. Domchek , Cecilia Dorfling , Thilo Dörk , Laure Dossus (4) , Mercedes Durán , Matthias Dürst , Bernd Dworniczak , Diana Eccles , Todd Edwards , Ros Eeles , Ursula Eilber , Bent Ejlertsen , Arif Ekici , Steve Ellis , Mingajeva Elvira , Study Embrace , Kevin Eng , Christoph Engel , D Gareth Evans , Peter Fasching , Sarah Ferguson , Sandra Fert Ferrer (5) , James M. Flanagan , Zachary Fogarty , Renée Fortner , Florentia Fostira , William Foulkes , George Fountzilas , Brooke Fridley , Tara Friebel , Eitan Friedman , Debra Frost , Patricia Ganz , Judy Garber , Maria Garcia , Vanesa Garcia-Barberan , Andrea Gehrig , Gemo Study Collaborators , Aleksandra Gentry-Maharaj , Anne-Marie Gerdes , Graham Giles , Rosalind Glasspool , Gord Glendon , Andrew K. Godwin , David E. Goldgar , Teodora Goranova , Martin Gore , Mark H. Greene , Jacek Gronwald , Stephen Gruber , Eric Hahnen , Christopher Haiman , Niclas Håkansson , Ute Hamann , Thomas Hansen , Patricia Harrington , Holly Harris , Jan Hauke , Hebon Study , Alexander Hein , Alex Henderson , Michelle Hildebrandt , Peter Hillemanns , Shirley Hodgson , Claus Høgdall , Estrid Høgdall , Frans B. L. Hogervorst , Helene Holland , Maartje Hooning , Karen Hosking , Ruea-Yea Huang , Peter Hulick , Jillian Hung , David J. Hunter , David Huntsman , Tomasz Huzarski , Evgeny Imyanitov , Claudine Isaacs , Edwin Iversen , Louise Izatt , Angel Izquierdo , Anna Jakubowska , Paul James , Ramunas Janavicius , Mats Jernetz , Allan Jensen , Uffe Birk Jensen , Esther M John , Sharon Johnatty , Michael E. Jones , Päivi Kannisto , Beth Karlan , Anthony Karnezis , Karin Kast , Kconfab Investigators , Catherine Kennedy , Elza Khusnutdinova , Lambertus Kiemeney , Johanna Kiiski , Sung-Won Kim , Susanne Kjaer , Martin Köbel , Reidun Kopperud , Torben A. Kruse , Jolanta Kupryjanczyk , Ava Kwong , Yael Laitman , Diether Lambrechts , Nerea Larrañaga , Melissa Larson , Conxi Lazaro , Nhu Le , Loic Le Marchand , Jong Won Lee , Shashikant Lele , Arto Leminen , Dominique Leroux (6) , Jenny Lester , Fabienne Lesueur (7, 8, 9) , Douglas Levine , Dong Liang , Clemens Liebrich , Jenna Lilyquist , Loren Lipworth , Jolanta Lissowska , Karen Lu , Jan Lubiński , Craig Luccarini , Lene Lundvall , Phuong Mai , Gustavo Mendoza-Fandiño , Siranoush Manoukian , Leon Massuger , Taymaa May , Sylvie Mazoyer (10) , Jessica Mcalpine , Valerie Mcguire , John Mclaughlin , Iain Mcneish , Hanne Meijers-Heijboer , Alfons Meindl , Usha Menon , Arjen Mensenkamp , Melissa Merritt , Roger Milne , Gillian Mitchell , Francesmary Modugno , Joanna Moes-Sosnowska , Melissa Moffitt , Marco Montagna , Kirsten Moysich , Anna Marie Mulligan , Jacob Musinsky , Katherine L. Nathanson , Lotte Nedergaard , Roberta Ness , Susan Neuhausen , Heli Nevanlinna , Dieter Niederacher , Robert Nussbaum , Kunle Odunsi , Edith Olah , Olufunmilayo Olopade , Håkan Olsson , Curtis Olswold , David O'Malley , Kai-Ren Ong , N Charlotte Onland-Moret , Opal Study Group , Nicholas Orr , Sandra Orsulic , Ana Osorio , Domenico Palli , Laura Papi , Tjoung-Won Park-Simon , James Paul , Celeste L. Pearce , Inge Søkilde Pedersen , Petra H.M. Peeters , Bernard Peissel , Ana Peixoto , Tanja Pejovic , Liisa M. Pelttari , Jennifer B. Permuth , Paolo Peterlongo , Lidia Pezzani , Georg Pfeiler , Kelly-Anne Phillips , Marion Piedmonte , Malcolm C. Pike , Anna M. Piskorz , Samantha R. Poblete , Timea Pocza , Elizabeth M. Poole , Bruce Poppe , Mary Porteous , Fabienne Prieur (11) , Darya Prokofyeva , Elizabeth Pugh , Miquel Angel Pujana , Pascal Pujol (12) , Paolo Radice , Johanna Rantala , Christine Rappaport-Fuerhauser , Gad Rennert , Kerstin Rhiem , Patricia Rice , Andrea Richardson , Mark Robson , Gustavo C Rodriguez , Cristina Rodríguez-Antona , Jane Romm , Matti A Rookus , Mary Anne Rossing , Joseph H. Rothstein , Anja Rudolph , Ingo B. Runnebaum , Helga B. Salvesen , Dale P Sandler , Minouk J. Schoemaker , Leigha Senter , V. Wendy Setiawan , Gianluca Severi (13, 14, 15) , Priyanka Sharma , Tameka Shelford , Nadeem Siddiqui , Lucy E Side , Weiva Sieh , Christian F. Singer , Hagay Sobol (16) , Honglin Song , Melissa C. Southey , Amanda B. Spurdle , Zsofia Stadler , Doris Steinemann , Dominique Stoppa-Lyonnet (2) , Lara E. Sucheston-Campbell , Grzegorz Sukiennicki , Rebecca Sutphen , Christian Sutter , Anthony J. Swerdlow , Csilla Szabo , Lukasz Szafron , Yen Y. Tan , Jack A. Taylor , Muy-Kheng Tea , Manuel R. Teixeira , Soo-Hwang Teo , Kathryn L. Terry , Pamela J. Thompson , Liv Cecilie Vestrheim Thomsen , Darcy L. Thull , Laima Tihomirova , Anna V. Tinker , Marc Tischkowitz , Silvia Tognazzo , Amanda Ewart Toland , Alicia Tone , Britton Trabert , Ruth C. Travis , Antonia Trichopoulou , Nadine Tung , Shelley S Tworoger , Anne M. van Altena , David van den Berg , Annemarie H. van Der Hout , Rob B van Der Luijt , Mattias van Heetvelde , Els van Nieuwenhuysen , Elizabeth J van Rensburg , Adriaan Vanderstichele , Raymonda Varon-Mateeva , Vega Ana , Digna Velez Edwards , Ignace Vergote , Robert A. Vierkant , Joseph Vijai , Athanassios Vratimos , Lisa Walker , Christine Walsh , Dorothea Wand , Shan Wang-Gohrke , Barbara Wappenschmidt , Penelope M. Webb , Clarice R Weinberg , Jeffrey N. Weitzel , Nicolas Wentzensen , Alice S. Whittemore , Juul T. Wijnen , Lynne R. Wilkens , Alicja Wolk , Michelle Woo , Xifeng Wu , Anna H. Wu , Hannah Yang , Drakoulis Yannoukakos , Argyrios Ziogas , Kristin K. Zorn , Steven A. Narod , Douglas F Easton , Christopher I. Amos , Joellen M. Schildkraut , Susan J. Ramus , Laura Ottini , Marc T. Goodman , Sue K. Park , Linda E. Kelemen , Harvey A Risch , Mads Thomassen , Kenneth Offit , Jacques Simard , Rita Katharina Schmutzler , Dennis Hazelett , Alvaro N. Monteiro , Fergus J Couch , Andrew Berchuck , Georgia Chenevix-Trench , Ellen Goode , Thomas A. Sellers , Simon A Gayther , Antonis C Antoniou , Paul D.P. Pharoah

1 Centre Léon Bérard [Lyon]
2 Service de Génétique Oncologique
3 CRLCC René Gauducheau
4 CIRC - IARC - Centre International de Recherche contre le Cancer - International Agency for Research on Cancer
5 Centre Hospitalier Métropole Savoie [Chambéry]
6 CHUGA - Centre Hospitalier Universitaire [CHU Grenoble]
7 Institut Curie [Paris]
8 Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe
9 Mines Paris - PSL (École nationale supérieure des mines de Paris)
10 UNICANCER/CRCL - Centre de Recherche en Cancérologie de Lyon
11 CHU ST-E - Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne]
12 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
13 UP11 UFR Médecine - Université Paris-Sud - Paris 11 - Faculté de médecine
14 IGR - Institut Gustave Roussy
15 Université Paris-Saclay
16 IPC - Institut Paoli-Calmettes

To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC. This identified three additional susceptibility loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC.

Domains: Genetics; Cancer; Human health and pathology

Catherine M. Phelan, Karoline B. Kuchenbaecker, Jonathan Tyrer, Siddhartha Kar, Kate Lawrenson, et al.. Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer. Nature Genetics, 2017, 49 (5), pp.680-691. ⟨10.1038/ng.3826⟩. ⟨hal-01778538⟩