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Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer

2016; Nature Portfolio; Volume: 7; Issue: 1 Linguagem: Inglês

10.1038/ncomms11375

2041-1723

Fergus J. Couch, Karoline Kuchenbaecker, Kyriaki Michailidou, Gustavo Mendoza-Fandiño, Silje Nord, Janna Lilyquist, Curtis Olswold, Emily Hallberg, Simona Agata, Habibul Ahsan, Kristiina Aittomäki, Christine B. Ambrosone, Irene L. Andrulis, Hoda Anton‐Culver, Volker Arndt, Banu K. Arun, Brita Arver, Monica Barile, Rósa B. Barkardóttir, Daniel Barrowdale, Lars Beckmann, Matthias W. Beckmann, Javier Benı́tez, Stephanie V. Blank, Carl Blomqvist, Natalia Bogdanova, Stig E. Bojesen, Manjeet K. Bolla, Bernardo Bonanni, Hiltrud Brauch, Hermann Brenner, Barbara Burwinkel, Saundra S. Buys, Trinidad Caldés, Maria A. Caligo, Federico Canzian, Jane Carpenter, Jenny Chang‐Claude, Stephen J. Chanock, Wendy K. Chung, Kathleen Claes, Angela Cox, Simon S. Cross, Julie M. Cunningham, Kamila Czene, Mary B. Daly, Francesca Damiola, Hatef Darabi, Miguel de la Hoya, Peter Devilee, Orland Dı́ez, Yuan Chun Ding, Riccardo Dolcetti, Susan M. Domchek, Cecilia M. Dorfling, Isabel dos‐Santos‐Silva, Martine Dumont, Alison M. Dunning, Diana Eccles, Hans Ehrencrona, Arif B. Ekici, Heather Eliassen, Ian O. Ellis, Peter A. Fasching, Jonine D. Figueroa, Dieter Flesch‐Janys, Asta Försti, Florentia Fostira, William D. Foulkes, Tara M. Friebel, Eitan Friedman, Debra Frost, Marike Gabrielson, Marilie D. Gammon, Patricia A. Ganz, Susan M. Gapstur, Judy E. Garber, Mia M. Gaudet, Simon A. Gayther, Anne–Marie Gerdes, Maya Ghoussaini, Graham G. Giles, Gord Glendon, Andrew K. Godwin, Mark S. Goldberg, David E. Goldgar, Anna González‐Neira, Mark H. Greene, Jacek Gronwald, Pascal Guénel, Marc J. Gunter, Lothar Haeberle, Christopher A. Haiman, Ute Hamann, Thomas van Overeem Hansen, Steven N. Hart, Sue Healey, Tuomas Heikkinen, Brian E. Henderson, Josef Herzog, Frans B.L. Hogervorst, Antoinette Hollestelle, Maartje J. Hooning, Robert N. Hoover, John L. Hopper, Keith Humphreys, David J. Hunter, Tomasz Huzarski, Evgeny N. Imyanitov, Claudine Isaacs, Anna Jakubowska, Paul A. James, Ramūnas Janavičius, Uffe Birk Jensen, Esther M. John, Michael E. Jones, Maria Kabisch, Siddhartha Kar, Beth Y. Karlan, Sofia Khan, Kay‐Tee Khaw, Muhammad G. Kibriya, Julia A. Knight, Yon‐Dschun Ko, Irene Konstantopoulou, Veli-Matti Kosma, Vessela N. Kristensen, Ava Kwong, Yael Laitman, Diether Lambrechts, Conxi Lázaro, Eunjung Lee, Loı̈c Le Marchand, Jenny Lester, Annika Lindblom, Noralane M. Lindor, Sara Lindström, Jianjun Liu, Jirong Long, Jan Lubiński, L. Phuong, Enes Makalic, Kathleen E. Malone, Graham J. Mann, Siranoush Manoukian, Sara Margolin, Frederik Marmé, John W.M. Martens, Lesley McGuffog, Alfons Meindl, Austin Miller, Roger L. Milne, Penelope Miron, Marco Montagna, Sylvie Mazoyer, Anna Marie Mulligan, Taru Muranen, Katherine L. Nathanson, Susan L. Neuhausen, Heli Nevanlinna, Børge G. Nordestgaard, Robert L. Nussbaum, Kenneth Offit, Edith Oláh, Olufunmilayo I. Olopade, Janet E. Olson, Ana Osório, Sue K. Park, Petra H. Peeters, Bernard Peissel, Paolo Peterlongo, Julian Peto, Catherine M. Phelan, Robert Pilarski, Bruce Poppe, Katri Pylkäs, Paolo Radice, Nazneen Rahman, Johanna Rantala, Christine Rappaport, Gad Rennert, Andrea Richardson, Mark E. Robson, Isabelle Romieu, Anja Rudolph, Emiel J. Rutgers, María‐José Sánchez, Regina M. Santella, Elinor J. Sawyer, Daniel F. Schmidt, Marjanka K. Schmidt, Rita K. Schmutzler, Fredrick R. Schumacher, Rodney J. Scott, Leigha Senter, Priyanka Sharma, Jacques Simard, Christian F. Singer, Olga M. Sinilnikova, Penny Soucy, Melissa C. Southey, Doris Steinemann, Marie Stenmark‐Askmalm, Dominique Stoppa‐Lyonnet, Anthony J. Swerdlow, Csilla I. Szabo, Rulla M. Tamimi, William Tapper, Manuel R. Teixeira, Soo‐Hwang Teo, Mary Beth Terry, Mads Thomassen, Deborah J. Thompson, Laima Tihomirova, Amanda E. Toland, Robert A.E.M. Tollenaar, Ian Tomlinson, Thérèse Truong, Helen Tsimiklis, Àlex Teulé, ­Rosario ­Tumino, Nadine Tung, Clare Turnbull, Giske Ursin, Carolien H. M. van Deurzen, Elizabeth J. van Rensburg, Raymonda Varon-Mateeva, Zhaoming Wang, Shan Wang‐Gohrke, Elisabete Weiderpass, Jeffrey N. Weitzel, Alice S. Whittemore, Hans Wildiers, Robert Winqvist, Xiaohong R. Yang, Drakoulis Yannoukakos, Song Yao, M. Pilar Zamora, Wei Zheng, Per Hall, Peter Kraft, Celine M. Vachon, Susan Slager, Georgia Chenevix‐Trench, Paul D.P. Pharoah, Álvaro N.A. Monteiro, Montserrat García‐Closas, Douglas F. Easton, Antonis C. Antoniou,

Genomics and Chromatin Dynamics

Abstract Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations ( P <5 × 10 −8 ) with oestrogen receptor (ER)-negative breast cancer and BRCA1 -associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci, we performed a meta-analysis of 11 genome-wide association studies (GWAS) consisting of 4,939 ER-negative cases and 14,352 controls, combined with 7,333 ER-negative cases and 42,468 controls and 15,252 BRCA1 mutation carriers genotyped on the iCOGS array. We identify four previously unidentified loci including two loci at 13q22 near KLF5 , a 2p23.2 locus near WDR43 and a 2q33 locus near PPIL3 that display genome-wide significant associations with ER-negative breast cancer. In addition, 19 known breast cancer risk loci have genome-wide significant associations and 40 had moderate associations ( P <0.05) with ER-negative disease. Using functional and eQTL studies we implicate TRMT61B and WDR43 at 2p23.2 and PPIL3 at 2q33 in ER-negative breast cancer aetiology. All ER-negative loci combined account for ∼11% of familial relative risk for ER-negative disease and may contribute to improved ER-negative and BRCA1 breast cancer risk prediction.