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

Catherine M Phelan, Karoline B. Kuchenbaecker, Jonathan P. Tyrer, Siddhartha P. Kar, Kate Lawrenson, Stacey J Winham, Joe Dennis, Ailith Pirie, Marjorie J. Riggan, Ganna Chornokur, Madalene A. Earp, Paulo C. Lyra, Janet M. Lee, Simon Coetzee, Jonathan Beesley, Lesley McGuffog, Penny Soucy, Ed Dicks, Andrew Lee, Daniel BarrowdaleJulie Lecarpentier, Goska Leslie, Cora M. Aalfs, Katja K.H. Aben, Marcia Adams, Julian Adlard, Irene L Andrulis, Hoda Anton-Culver, Natalia Antonenkova, Gerasimos Aravantinos, Norbert Arnold, Banu K. Arun, Brita Arver, Jacopo Azzollini, Judith Balmaña, Susana N. Banerjee, Laure Barjhoux, Rosa B. Barkardottir, Yukie Tarumi Bean, Matthias W. Beckmann, Alicia Beeghly-Fadiel, Javier Benitez, Marina Bermisheva, Marcus Q. Bernardini, Michael J. Birrer, Line Bjorge, Amanda Black, Kenneth Blankstein, Marinus J. Blok, Clara Bodelon, Natalia Bogdanova, Anders Miki Bojesen, Bernardo Bonanni, Åke Borg, Angela R. Bradbury, James D Brenton, Carole Brewer, Louise Brinton, Per Broberg, Angela Brooks-Wilson, Fiona Bruinsma, Joan Brunet, Bruno Buecher, Ralf Butzow, Saundra S. Buys, Trinidad Caldes, Maria A. Caligo, Ian Campbell, Rikki Cannioto, Michael E. Carney, Terence Cescon, Salina B. Chan, Jenny Chang-Claude, Stephen J Chanock, Xiao Qing Chen, Yoke Eng Chiew, Jocelyne Chiquette, Wendy K. Chung, Kathleen B.M. Claes, Thomas Conner, Linda S. Cook, Jackie Cook, Daniel W. Cramer, Julie M. Cunningham, Aimee A. D'Aloisio, Mary B Daly, Francesca Damiola, Sakaeva Dina Damirovna, Agnieszka Dansonka-Mieszkowska, Fanny Dao, Rosemarie Davidson, Anna DeFazio, Capucine Delnatte, Kimberly F. Doheny, Orland Diez, Yuan Chun Ding, Jennifer Anne Doherty, Susan M. Domchek, Cecilia M. Dorfling, Thilo Dörk, Laure Dossus, Mercedes Duran, Matthias Dürst, Bernd Dworniczak, Diana M Eccles, Todd Edwards, Ros Eeles, Ursula Eilber, Bent Ejlertsen, Arif B Ekici, Steve Ellis, Mingajeva Elvira, Kevin H. Eng, Christoph Engel, D. Gareth Evans, Peter A. Fasching, Sarah Ferguson, Sandra Fert Ferrer, James M. Flanagan, Zachary C Fogarty, Renée T. Fortner, Florentia Fostira, William D Foulkes, George Fountzilas, Brooke L. Fridley, Tara M. Friebel, Eitan Friedman, Debra Frost, Patricia A. Ganz, Judy Garber, María J. García, Vanesa Garcia-Barberan, Andrea Gehrig, Aleksandra Gentry-Maharaj, Anne-Marie Gerdes, Graham G. Giles, Rosalind M Glasspool, Gord Glendon, Andrew K. Godwin, David E. Goldgar, Teodora Goranova, Martin Gore, Mark H. Greene, Jacek Gronwald, Stephen Gruber, Eric T Hahnen, Christopher A Haiman, Niclas Håkansson, Ute Hamann, Thomas V.O. Hansen, Patricia A. Harrington, Holly R. Harris, Jan Hauke, Alexander Hein, Alex Henderson, Michelle A T Hildebrandt, Peter Hillemanns, Shirley Hodgson, Claus K. Høgdall, Estrid Høgdall, Frans B.L. Hogervorst, Helene Holland, Maartje J Hooning, Karen Hosking, Ruea Yea Huang, Peter J. Hulick, Jillian Hung, David J. Hunter, David G Huntsman, Tomasz Huzarski, Evgeny N. Imyanitov, Claudine Janet Diana Isaacs, Edwin S. Iversen, Louise Izatt, Angel Izquierdo, Anna Jakubowska, Paul James, Ramunas Janavicius, Mats Jernetz, Allan Jensen, Uffe Birk Jensen, Esther M. John, Sharon E Johnatty, Michael E. Jones, Päivi Kannisto, Beth Y. Karlan, Anthony N Karnezis, Karin Kast, Catherine J. Kennedy, Elza Khusnutdinova, Lambertus A. Kiemeney, Johanna I. Kiiski, Sung Won Kim, Susanne Kruger Ruger Kjaer, Martin Köbel, Reidun K Kopperud, Torben A. Kruse, Jolanta Kupryjanczyk, Ava Kwong, Yael Laitman, Diether Lambrechts, Nerea Larrañaga, Melissa C. Larson, Conxi Lazaro, Nhu D. Le, Loic Le Marchand, Jong Won Lee, Shashikant B. Lele, Arto Leminen, Dominique Leroux, Jenny Lester, Fabienne Lesueur, Douglas A. Levine, Dong Liang, Clemens Liebrich, Jenna Lilyquist, Loren Lipworth, Jolanta Lissowska, Karen H. Lu, Jan Lubiński, Craig Luccarini, Lene Lundvall, Phuong L Mai, Gustavo Mendoza-Fandiño, Siranoush Manoukian, Leon F A G Massuger, Taymaa May, Sylvie Mazoyer, Jessica N. McAlpine, Valerie McGuire, John R McLaughlin, Iain A McNeish, Hanne Meijers-Heijboer, Alfons Meindl, Usha N Menon, Arjen R. Mensenkamp, Melissa A. Merritt, Roger L Milne, Gillian W E Mitchell, Francesmary Modugno, Joanna Moes-Sosnowska, Melissa Moffitt, Marco Montagna, Kirsten B Moysich, Anna Marie Mulligan, Jacob Musinsky, Katherine L Nathanson, Lotte Nedergaard, Roberta B Ness, Melissa C. Southey, HEBON Study, AOCS Study Group, EMBRACE Study, OPAL study group, kConFab Investigators, GEMO Study Collaborators

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Abstract

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.

Original languageEnglish
Pages (from-to)680-691
Number of pages12
JournalNature Genetics
Volume49
Issue number5
DOIs
Publication statusPublished - 1 May 2017

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