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

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.

DOI: 10.1038/ng.3826

Projects: GC-HBOC - German Consortium for Hereditary Breast and Ovarian Cancer

Publication type: Journal article

Journal: Nature genetics

Human Diseases: Hereditary breast ovarian cancer syndrome

Citation: Nat Genet 49(5):680-691

Date Published: 1st May 2017

Registered Mode: imported from a bibtex file

Authors: 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 Barrowdale, Julie 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 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 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 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 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 Glasspool, Gord Glendon, Andrew K. Godwin, David E. Goldgar, Teodora Goranova, Martin Gore, Mark H. Greene, Jacek Gronwald, Stephen Gruber, Eric 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 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 Johnatty, Michael E. Jones, Päivi Kannisto, Beth Y. Karlan, Anthony Karnezis, Karin Kast, Catherine J. Kennedy, Elza Khusnutdinova, Lambertus A. Kiemeney, Johanna I. Kiiski, Sung-Won Kim, Susanne K. 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 Lubinński, 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 McNeish, Hanne Meijers-Heijboer, Alfons Meindl, Usha Menon, Arjen R. Mensenkamp, Melissa A. Merritt, Roger L. Milne, Gillian 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, Susan L. Neuhausen, Heli Nevanlinna, Dieter Niederacher, Robert L. Nussbaum, Kunle Odunsi, Edith Olah, Olufunmilayo I. Olopade, Håkan Olsson, Curtis Olswold, David M. O’Malley, Kai-Ren Ong, N. Charlotte Onland-Moret, 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 E. Porteous, Fabienne Prieur, Darya Prokofyeva, Elizabeth Pugh, Miquel Angel Pujana, Pascal Pujol, 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, Priyanka Sharma, Tameka Shelford, Nadeem Siddiqui, Lucy E. Side, Weiva Sieh, Christian F. Singer, Hagay Sobol, Honglin Song, Melissa C. Southey, Amanda B. Spurdle, Zsofia Stadler, Doris Steinemann, Dominique Stoppa-Lyonnet, Lara E. Sucheston-Campbell, Grzegorz Sukiennicki, Rebecca Sutphen, Christian Sutter, Anthony J. Swerdlow, Csilla I. 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, Ana Vega, 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 L. Goode, Thomas A. Sellers, Simon A. Gayther, Antonis C. Antoniou, Paul D. P. Pharoah

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Phelan, C. M., Kuchenbaecker, K. B., Tyrer, J. P., Kar, S. P., Lawrenson, K., Winham, S. J., Dennis, J., Pirie, A., Riggan, M. J., Chornokur, G., Earp, M. A., Lyra, P. C., Jr, Lee, J. M., Coetzee, S., Beesley, J., McGuffog, L., Soucy, P., Dicks, E., Lee, A., … Pharoah, P. D. P. (2017). Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer. In Nature Genetics (Vol. 49, Issue 5, pp. 680–691). Springer Science and Business Media LLC. https://doi.org/10.1038/ng.3826
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