Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer.
Journal: Nature Genetics
Published:
Abstract
Most common breast cancer susceptibility variants have been identified through genome-wide association studies (GWAS) of predominantly estrogen receptor (ER)-positive disease. 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.
Authors
Roger Milne, Karoline Kuchenbaecker, Kyriaki Michailidou, Jonathan Beesley, Siddhartha Kar, Sara Lindström, Shirley Hui, Audrey Lemaçon, Penny Soucy, Joe Dennis, Xia Jiang, Asha Rostamianfar, Hilary Finucane, Manjeet Bolla, Lesley Mcguffog, Qin Wang, Cora Aalfs, Julian Adlard, Simona Agata, Shahana Ahmed, Habibul Ahsan, Kristiina Aittomäki, Fares Al Ejeh, Jamie Allen, Christine Ambrosone, Christopher Amos, Irene Andrulis, Hoda Anton Culver, Natalia Antonenkova, Volker Arndt, Norbert Arnold, Kristan Aronson, Bernd Auber, Paul Auer, Margreet G E Ausems, Jacopo Azzollini, François Bacot, Judith Balmaña, Monica Barile, Laure Barjhoux, Rosa Barkardottir, Myrto Barrdahl, Daniel Barnes, Daniel Barrowdale, Caroline Baynes, Matthias Beckmann, Javier Benitez, Marina Bermisheva, Leslie Bernstein, Yves-jean Bignon, Kathleen Blazer, Marinus Blok, Carl Blomqvist, William Blot, Kristie Bobolis, Bram Boeckx, Natalia Bogdanova, Anders Bojesen, Stig Bojesen, Bernardo Bonanni, Anne-lise Børresen Dale, Aniko Bozsik, Angela Bradbury, Judith Brand, Hiltrud Brauch, Hermann Brenner, Brigitte Bressac De Paillerets, Carole Brewer, Louise Brinton, Per Broberg, Angela Brooks Wilson, Joan Brunet, Thomas Brüning, Barbara Burwinkel, Saundra Buys, Jinyoung Byun, Qiuyin Cai, Trinidad Caldés, Maria Caligo, Ian Campbell, Federico Canzian, Olivier Caron, Angel Carracedo, Brian Carter, J Castelao, Laurent Castera, Virginie Caux Moncoutier, Salina Chan, Jenny Chang Claude, Stephen Chanock, Xiaoqing Chen, Ting-yuan Cheng, Jocelyne Chiquette, Hans Christiansen, Kathleen B Claes, Christine Clarke, Thomas Conner, Don Conroy, Jackie Cook, Emilie Cordina Duverger, Sten Cornelissen, Isabelle Coupier, Angela Cox, David Cox, Simon Cross, Katarina Cuk, Julie Cunningham, Kamila Czene, Mary Daly, Francesca Damiola, Hatef Darabi, Rosemarie Davidson, Kim De Leeneer, Peter Devilee, Ed Dicks, Orland Diez, Yuan Ding, Nina Ditsch, Kimberly Doheny, Susan Domchek, Cecilia Dorfling, Thilo Dörk, Isabel Dos Santos Silva, Stéphane Dubois, Pierre-antoine Dugué, Martine Dumont, Alison Dunning, Lorraine Durcan, Miriam Dwek, Bernd Dworniczak, Diana Eccles, Ros Eeles, Hans Ehrencrona, Ursula Eilber, Bent Ejlertsen, Arif Ekici, A Eliassen, Christoph Engel, Laura Fachal, Laurence Faivre, Peter Fasching, Ulrike Faust, Jonine Figueroa, Dieter Flesch Janys, Olivia Fletcher, Henrik Flyger, William Foulkes, Eitan Friedman, Lin Fritschi, Debra Frost, Marike Gabrielson, Pragna Gaddam, Marilie Gammon, Patricia Ganz, Susan Gapstur, Judy Garber, Vanesa Garcia Barberan, José García Sáenz, Mia Gaudet, Marion Gauthier Villars, Andrea Gehrig, Vassilios Georgoulias, Anne-marie Gerdes, Gord Glendon, Andrew Godwin, Mark Goldberg, David Goldgar, Anna González Neira, Paul Goodfellow, Mark Greene, Grethe Alnæs, Mervi Grip, Jacek Gronwald, Anne Grundy, Daphne Gschwantler Kaulich, Pascal Guénel, Qi Guo, Lothar Haeberle, Eric Hahnen, Christopher Haiman, Niclas Håkansson, Emily Hallberg, Ute Hamann, Nathalie Hamel, Susan Hankinson, Thomas Hansen, Patricia Harrington, Steven Hart, Jaana Hartikainen, Catherine Healey, Alexander Hein, Sonja Helbig, Alex Henderson, Belynda Hicks, Peter Hillemanns, Shirley Hodgson, Frans Hogervorst, Antoinette Hollestelle, Maartje Hooning, Bob Hoover, John Hopper, Chunling Hu, Guanmengqian Huang, Peter Hulick, Keith Humphreys, David Hunter, Evgeny Imyanitov, Claudine Isaacs, Motoki Iwasaki, Louise Izatt, Anna Jakubowska, Paul James, Ramunas Janavicius, Wolfgang Janni, Uffe Jensen, Esther John, Nichola Johnson, Kristine Jones, Michael Jones, Arja Jukkola Vuorinen, Rudolf Kaaks, Maria Kabisch, Katarzyna Kaczmarek, Daehee Kang, Karin Kast, Renske Keeman, Michael Kerin, Carolien Kets, Machteld Keupers, Elza Khusnutdinova, Johanna Kiiski, Sung-won Kim, Julia Knight, Irene Konstantopoulou, Veli-matti Kosma, Vessela Kristensen, Torben Kruse, Ava Kwong, Anne-vibeke Lænkholm, Yael Laitman, Fiona Lalloo, Diether Lambrechts, Keren Landsman, Christine Lasset, Conxi Lazaro, Loic Le Marchand, Julie Lecarpentier, Andrew Lee, Eunjung Lee, Jong Lee, Min Lee, Flavio Lejbkowicz, Fabienne Lesueur, Jingmei Li, Jenna Lilyquist, Anne Lincoln, Annika Lindblom, Jolanta Lissowska, Wing-yee Lo, Sibylle Loibl, Jirong Long, Jennifer Loud, Jan Lubinski, Craig Luccarini, Michael Lush, Robert Macinnis, Tom Maishman, Enes Makalic, Ivana Kostovska, Kathleen Malone, Siranoush Manoukian, Joann Manson, Sara Margolin, John W Martens, Maria Martinez, Keitaro Matsuo, Dimitrios Mavroudis, Sylvie Mazoyer, Catriona Mclean, Hanne Meijers Heijboer, Primitiva Menéndez, Jeffery Meyer, Hui Miao, Austin Miller, Nicola Miller, Gillian Mitchell, Marco Montagna, Kenneth Muir, Anna Mulligan, Claire Mulot, Sue Nadesan, Katherine Nathanson, Susan Neuhausen, Heli Nevanlinna, Ines Nevelsteen, Dieter Niederacher, Sune Nielsen, Aaron Norman, Robert Nussbaum, Edith Olah, Olufunmilayo Olopade, Janet Olson, Curtis Olswold, Kai-ren Ong, Jan Oosterwijk, Nick Orr, Ana Osorio, V Pankratz, Laura Papi, Tjoung-won Park Simon, Ylva Paulsson Karlsson, Rachel Lloyd, Inge Pedersen, Bernard Peissel, Ana Peixoto, Jose Perez, Paolo Peterlongo, Julian Peto, Georg Pfeiler, Catherine Phelan, Mila Pinchev, Dijana Plaseska Karanfilska, Bruce Poppe, Mary Porteous, Ross Prentice, Nadege Presneau, Darya Prokofieva, Elizabeth Pugh, Miquel Pujana, Katri Pylkäs, Brigitte Rack, Paolo Radice, Nazneen Rahman, Johanna Rantala, Christine Rappaport Fuerhauser, Gad Rennert, Hedy Rennert, Valerie Rhenius, Kerstin Rhiem, Andrea Richardson, Gustavo Rodriguez, Atocha Romero, Jane Romm, Matti Rookus, Anja Rudolph, Thomas Ruediger, Emmanouil Saloustros, Joyce Sanders, Dale Sandler, Suleeporn Sangrajrang, Elinor Sawyer, Daniel Schmidt, Minouk Schoemaker, Fredrick Schumacher, Peter Schürmann, Lukas Schwentner, Christopher Scott, Rodney Scott, Sheila Seal, Leigha Senter, Caroline Seynaeve, Mitul Shah, Priyanka Sharma, Chen-yang Shen, Xin Sheng, Hermela Shimelis, Martha Shrubsole, Xiao-ou Shu, Lucy Side, Christian Singer, Christof Sohn, Melissa Southey, John Spinelli, Amanda Spurdle, Christa Stegmaier, Dominique Stoppa Lyonnet, Grzegorz Sukiennicki, Harald Surowy, Christian Sutter, Anthony Swerdlow, Csilla Szabo, Rulla Tamimi, Yen Tan, Jack Taylor, Maria-isabel Tejada, Maria Tengström, Soo Teo, Mary Terry, Daniel Tessier, Alex Teulé, Kathrin Thöne, Darcy Thull, Maria Tibiletti, Laima Tihomirova, Marc Tischkowitz, Amanda Toland, Rob A E Tollenaar, Ian Tomlinson, Ling Tong, Diana Torres, Martine Tranchant, Thérèse Truong, Kathy Tucker, Nadine Tung, Jonathan Tyrer, Hans-ulrich Ulmer, Celine Vachon, Christi Van Asperen, David Van Den Berg, Ans M Van Den Ouweland, Elizabeth Van Rensburg, Liliana Varesco, Raymonda Varon Mateeva, Ana Vega, Alessandra Viel, Joseph Vijai, Daniel Vincent, Jason Vollenweider, Lisa Walker, Zhaoming Wang, Shan Wang Gohrke, Barbara Wappenschmidt, Clarice Weinberg, Jeffrey Weitzel, Camilla Wendt, Jelle Wesseling, Alice Whittemore, Juul Wijnen, Walter Willett, Robert Winqvist, Alicja Wolk, Anna Wu, Lucy Xia, Xiaohong Yang, Drakoulis Yannoukakos, Daniela Zaffaroni, Wei Zheng, Bin Zhu, Argyrios Ziogas, Elad Ziv, Kristin Zorn, Manuela Gago Dominguez, Arto Mannermaa, Håkan Olsson, Manuel Teixeira, Jennifer Stone, Kenneth Offit, Laura Ottini, Sue Park, Mads Thomassen, Per Hall, Alfons Meindl, Rita Schmutzler, Arnaud Droit, Gary Bader, Paul D Pharoah, Fergus Couch, Douglas Easton, Peter Kraft, Georgia Chenevix Trench, Montserrat García Closas, Marjanka Schmidt, Antonis Antoniou, Jacques Simard
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