Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer

Roger L. Milne, Karoline B. Kuchenbaecker, Kyriaki Michailidou, Jonathan Beesley, Siddhartha Kar, Sara Lindström, Shirley Hui, Audrey Lemaçon, Penny Soucy, Joe Dennis, Xia Jiang, Asha Rostamianfar, Hilary Finucane, Manjeet K. Bolla, Lesley McGuffog, Qin Wang, Cora M. Aalfs, Investigators Abctctb, Marcia Adams, Julian AdlardSimona Agata, Shahana Ahmed, Habibul Ahsan, Kristiina Äki Aittom, Al Ejeh Fares, Jamie Allen, Christine B. Ambrosone, Christopher I. Amos, Irene L. Andrulis, Hoda Anton-Culver, Natalia N. Antonenkova, Volker Arndt, Norbert Arnold, Kristan J. Aronson, Bernd Auber, Paul L. Auer, Margreet G.M. Ausems, Jacopo Azzollini, Bacot François, Judith Nã Balma, Monica Barile, Laure Barjhoux, Rosa B. Barkardottir, Myrto Barrdahl, Daniel Barnes, Daniel Barrowdale, Caroline Baynes, Matthias W. Beckmann, Javier Benitez, Marina Bermisheva, Leslie Bernstein, Yves Jean Bignon, Kathleen R. Blazer, Marinus J. Blok, Carl Blomqvist, William Blot, Kristie Bobolis, Bram Boeckx, Natalia V. 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Goldgar, Anna González-Neira, Paul Goodfellow, Mark H. Greene, Grethe Alnæs I. Grenaker, Mervi Grip, Jacek Gronwald, Anne Grundy, Daphne Kaulich Gschwantler, Pascal Guénel, Qi Guo, Lothar Haeberle, Eric Hahnen, Christopher A. Haiman, Niclas Håkansson, Emily Hallberg, Ute Hamann, Nathalie Hamel, Susan Hankinson, Thomas V. Hansen, Patricia Harrington, Steven N. Hart, Jaana M. Hartikainen, Catherine S. Healey, Alexander Hein, Sonja Helbig, Alex Henderson, Jane Heyworth, Belynda Hicks, Peter Hillemanns, Shirley Hodgson, Frans B. Hogervorst, Antoinette Hollestelle, Maartje J. Hooning, Bob Hoover, John L. Hopper, Chunling Hu, Guanmengqian Huang, Peter J. Hulick, Keith Humphreys, David J. Hunter, Evgeny N. Imyanitov, Claudine Isaacs, Motoki Iwasaki, Louise Izatt, Anna Jakubowska, Paul James, Ramunas Janavicius, Wolfgang Janni, Uffe Birk Jensen, Esther M. 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McLaes, Flesch Janys Dieter, Daphne Gschwantler-Kaulich, Julie Lecarpentier, Andrew Lee, Eunjung Lee, Jong Lee Won, Min Hyuk Lee, Flavio Lejbkowicz, Fabienne Lesueur, Jingmei Li, Jenna Lilyquist, Anne Lincoln, Annika Lindblom, Jolanta Lissowska, Wing Yee Lo, Sibylle Loibl, Jirong Long, Jennifer T. Loud, Jan Lubinski, Craig Luccarini, Michael Lush, Robert J. MacInnis, Tom Maishman, Enes Makalic, Ivana Maleva Kostovska, Kathleen E. Malone, Manoukian Siranoush, Joann E. Manson, Sara Margolin, John W. Martens, Maria Elena Martinez, Keitaro Matsuo, Dimitrios Mavroudis, Sylvie Mazoyer, Catriona McLean, Hanne Meijers-Heijboer, Primitiva Menéndez, Jeffery Meyer, Hui Miao, Nicola Miller, Gillian Mitchell, Marco Montagna, Kenneth Muir, Anna Marie Mulligan, Claire Mulot, Sue Nadesan, Katherine L. Nathanson, Susan L. Neuhausen, Heli Nevanlinna, Ines Nevelsteen, Dieter Niederacher, Sune F. Nielsen, Børge G. Nordestgaard, Aaron Norman, Robert L. Nussbaum, Edith Olah, Olufunmilayo I. 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Scott, Sheila Seal, Leigha Senter, Caroline Seynaeve, Mitul Shah, Priyanka Sharma, Chen Yang Shen, Xin Sheng, Hermela Shimelis, Martha J. Shrubsole, Xiao Ou Shu, Lucy E. Side, Christian F. Singer, Christof Sohn, Melissa C. Southey, John J. Spinelli, Amanda B. Spurdle, Christa Stegmaier, Dominique Stoppa-Lyonnet, Grzegorz Sukiennicki, Harald Surowy, Christian Sutter, Anthony Swerdlow, Csilla I. Szabo, Rulla M. Tamimi, Yen Y. Tan, Jack A. Taylor, Maria Isabel Tejada, Maria Tengström, Soo H. Teo, Mary B. Terry, Daniel C. Tessier, Alex E. Teul, Kathrin Thöne, Darcy L. Thull, Maria Grazia Tibiletti, Laima Tihomirova, Marc Tischkowitz, Amanda E. Toland, Rob A.M. Tollenaar, Ian Tomlinson, Ling Tong, Diana Torres, Martine Tranchant, Thérèse Truong, Kathy Tucker, Nadine Tung, Jonathan Tyrer, Hans Ulrich Ulmer, Celine Vachon, Van Asperen J. Christi, David Van Den Berg, Ans M.Vanden Ouweland, Elizabeth J. 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Research output: Contribution to journalArticlepeer-review

119 Scopus citations

Abstract

Most common breast cancer susceptibility variants have been identified through genome-wide association studies (GWAS) of predominantly estrogen receptor (ER)-positive disease1. We conducted a GWAS using 21,468 ER-negative cases and 100,594 controls combined with 18,908 BRCA1 mutation carriers (9,414 with breast cancer), all of European origin. We identified independent associations at P < 5 × 10-8 with ten variants at nine new loci. At P < 0.05, we replicated associations with 10 of 11 variants previously reported in ER-negative disease or BRCA1 mutation carrier GWAS and observed consistent associations with ER-negative disease for 105 susceptibility variants identified by other studies. These 125 variants explain approximately 16% of the familial risk of this breast cancer subtype. There was high genetic correlation (0.72) between risk of ER-negative breast cancer and breast cancer risk for BRCA1 mutation carriers. These findings may lead to improved risk prediction and inform further fine-mapping and functional work to better understand the biological basis of ER-negative breast cancer.

Original languageEnglish (US)
Pages (from-to)1767-1778
Number of pages12
JournalNature Genetics
Volume49
Issue number12
DOIs
StatePublished - Dec 1 2017

ASJC Scopus subject areas

  • Genetics

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