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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-12

AUTHORS

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, ABCTB Investigators, Marcia Adams, Julian Adlard, Simona Agata, Shahana Ahmed, Habibul Ahsan, Kristiina Aittomäki, Fares Al-Ejeh, 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 E M Ausems, Jacopo Azzollini, François Bacot, Judith Balmaña, 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 Bogdanova, Anders Bojesen, Stig E Bojesen, Bernardo Bonanni, Anne-Lise Børresen-Dale, Aniko Bozsik, Angela R Bradbury, Judith S 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 S Buys, Jinyoung Byun, Qiuyin Cai, Trinidad Caldés, Maria A Caligo, Ian Campbell, Federico Canzian, Olivier Caron, Angel Carracedo, Brian D Carter, J Esteban Castelao, Laurent Castera, Virginie Caux-Moncoutier, Salina B Chan, Jenny Chang-Claude, Stephen J Chanock, Xiaoqing Chen, Ting-Yuan David Cheng, Jocelyne Chiquette, Hans Christiansen, Kathleen B M Claes, Christine L Clarke, Thomas Conner, Don M Conroy, Jackie Cook, Emilie Cordina-Duverger, Sten Cornelissen, Isabelle Coupier, Angela Cox, David G Cox, Simon S Cross, Katarina Cuk, Julie M Cunningham, Kamila Czene, Mary B Daly, Francesca Damiola, Hatef Darabi, Rosemarie Davidson, Kim De Leeneer, Peter Devilee, Ed Dicks, Orland Diez, Yuan Chun Ding, Nina Ditsch, Kimberly F Doheny, Susan M Domchek, Cecilia M Dorfling, Thilo Dörk, Isabel dos-Santos-Silva, Stéphane Dubois, Pierre-Antoine Dugué, Martine Dumont, Alison M Dunning, Lorraine Durcan, Miriam Dwek, Bernd Dworniczak, Diana Eccles, Ros Eeles, Hans Ehrencrona, Ursula Eilber, Bent Ejlertsen, Arif B Ekici, A Heather Eliassen, EMBRACE, Christoph Engel, Mikael Eriksson, Laura Fachal, Laurence Faivre, Peter A Fasching, Ulrike Faust, Jonine Figueroa, Dieter Flesch-Janys, Olivia Fletcher, Henrik Flyger, William D Foulkes, Eitan Friedman, Lin Fritschi, Debra Frost, Marike Gabrielson, Pragna Gaddam, Marilie D Gammon, Patricia A Ganz, Susan M Gapstur, Judy Garber, Vanesa Garcia-Barberan, José A García-Sáenz, Mia M Gaudet, Marion Gauthier-Villars, Andrea Gehrig, GEMO Study Collaborators, Vassilios Georgoulias, Anne-Marie Gerdes, Graham G Giles, Gord Glendon, Andrew K Godwin, Mark S Goldberg, David E Goldgar, Anna González-Neira, Paul Goodfellow, Mark H Greene, Grethe I Grenaker Alnæs, Mervi Grip, Jacek Gronwald, Anne Grundy, Daphne Gschwantler-Kaulich, Pascal Guénel, Qi Guo, Lothar Haeberle, Eric Hahnen, Christopher A Haiman, Niclas Håkansson, Emily Hallberg, Ute Hamann, Nathalie Hamel, Susan Hankinson, Thomas V O Hansen, Patricia Harrington, Steven N Hart, Jaana M Hartikainen, Catherine S Healey, HEBON, 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 John, Nichola Johnson, Kristine Jones, Michael Jones, Arja Jukkola-Vuorinen, Rudolf Kaaks, Maria Kabisch, Katarzyna Kaczmarek, Daehee Kang, Karin Kast, ConFab/AOCS Investigators, Renske Keeman, Michael J Kerin, Carolien M Kets, Machteld Keupers, Sofia Khan, Elza Khusnutdinova, Johanna I Kiiski, Sung-Won Kim, Julia A Knight, Irene Konstantopoulou, Veli-Matti Kosma, Vessela N Kristensen, Torben A 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 Won Lee, 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, Siranoush Manoukian, JoAnn E Manson, Sara Margolin, John W M Martens, Maria Elena 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 Marie Mulligan, Claire Mulot, Sue Nadesan, Katherine L Nathanson, NC Collaborators, Susan L Neuhausen, Heli Nevanlinna, Ines Nevelsteen, Dieter Niederacher, Sune F Nielsen, Børge G Nordestgaard, Aaron Norman, Robert L Nussbaum, Edith Olah, Olufunmilayo I Olopade, Janet E Olson, Curtis Olswold, Kai-ren Ong, Jan C Oosterwijk, Nick Orr, Ana Osorio, V Shane Pankratz, Laura Papi, Tjoung-Won Park-Simon, Ylva Paulsson-Karlsson, Rachel Lloyd, Inge Søkilde Pedersen, Bernard Peissel, Ana Peixoto, Jose I A Perez, Paolo Peterlongo, Julian Peto, Georg Pfeiler, Catherine M Phelan, Mila Pinchev, Dijana Plaseska-Karanfilska, Bruce Poppe, Mary E Porteous, Ross Prentice, Nadege Presneau, Darya Prokofieva, Elizabeth Pugh, Miquel Angel Pujana, Katri Pylkäs, Brigitte Rack, Paolo Radice, Nazneen Rahman, Johanna Rantala, Christine Rappaport-Fuerhauser, Gad Rennert, Hedy S Rennert, Valerie Rhenius, Kerstin Rhiem, Andrea Richardson, Gustavo C Rodriguez, Atocha Romero, Jane Romm, Matti A Rookus, Anja Rudolph, Thomas Ruediger, Emmanouil Saloustros, Joyce Sanders, Dale P Sandler, Suleeporn Sangrajrang, Elinor J Sawyer, Daniel F Schmidt, Minouk J Schoemaker, Fredrick Schumacher, Peter Schürmann, Lukas Schwentner, Christopher Scott, Rodney J 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 Teulé, Kathrin Thöne, Darcy L Thull, Maria Grazia Tibiletti, Laima Tihomirova, Marc Tischkowitz, Amanda E Toland, Rob A E M Tollenaar, Ian Tomlinson, Ling Tong, Diana Torres, Martine Tranchant, Thérèse Truong, Kathy Tucker, Nadine Tung, Jonathan Tyrer, Hans-Ulrich Ulmer, Celine Vachon, Christi J van Asperen, David Van Den Berg, Ans M W van den Ouweland, Elizabeth J 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 R Weinberg, Jeffrey N Weitzel, Camilla Wendt, Jelle Wesseling, Alice S Whittemore, Juul T Wijnen, Walter Willett, Robert Winqvist, Alicja Wolk, Anna H Wu, Lucy Xia, Xiaohong R Yang, Drakoulis Yannoukakos, Daniela Zaffaroni, Wei Zheng, Bin Zhu, Argyrios Ziogas, Elad Ziv, Kristin K Zorn, Manuela Gago-Dominguez, Arto Mannermaa, Håkan Olsson, Manuel R Teixeira, Jennifer Stone, Kenneth Offit, Laura Ottini, Sue K Park, Mads Thomassen, Per Hall, Alfons Meindl, Rita K Schmutzler, Arnaud Droit, Gary D Bader, Paul D P Pharoah, Fergus J Couch, Douglas F Easton, Peter Kraft, Georgia Chenevix-Trench, Montserrat García-Closas, Marjanka K Schmidt, Antonis C Antoniou, Jacques Simard

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. More... »

PAGES

1767

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  • Journal

    TITLE

    Nature Genetics

    ISSUE

    12

    VOLUME

    49

    Author Affiliations

  • University of Melbourne
  • Wellcome Sanger Institute
  • Cyprus Institute of Neurology and Genetics
  • QIMR Berghofer Medical Research Institute
  • University of Cambridge
  • Harvard University
  • University of Toronto
  • Université Laval
  • Massachusetts Institute of Technology
  • Academic Medical Center
  • Johns Hopkins University
  • Chapel Allerton Hospital
  • Istituto Oncologico Veneto
  • Roswell Park Cancer Institute
  • Dartmouth College
  • University of California, Irvine
  • German Cancer Research Center
  • Queen's University
  • Hannover Medical School
  • University of Wisconsin–Milwaukee
  • University Medical Center Utrecht
  • Istituto Nazionale dei Tumori
  • McGill University and Génome Québec Innovation Centre
  • Hospital Universitari Vall d'Hebron
  • European Institute of Oncology
  • Centre Léon Bérard
  • University of Iceland
  • Centre for Biomedical Network Research on Rare Diseases
  • Institute of Biochemistry and Genetics of Ufa Scientific Centre
  • City Of Hope National Medical Center
  • Maastricht University Medical Centre
  • International Epidemiology Institute
  • KU Leuven
  • Vejle Sygehus
  • University of Copenhagen
  • Oslo University Hospital
  • National Institute of Oncology
  • Karolinska Institute
  • Institut Gustave Roussy
  • Royal Devon and Exeter Hospital
  • National Cancer Institute
  • Lund University
  • Simon Fraser University
  • Institut Català d'Oncologia
  • Ruhr University Bochum
  • Huntsman Cancer Institute
  • Hospital Clínico San Carlos
  • Azienda Ospedaliera Universitaria Pisana
  • University of Santiago de Compostela
  • American Cancer Society
  • UniCancer Group
  • Institute Curie
  • University of California, San Francisco
  • University Cancer Center Hamburg
  • Hôpital du Saint-Sacrement
  • Ghent University
  • University of Sydney
  • Sheffield Children's Hospital
  • University of Paris-Sud
  • Antoni van Leeuwenhoek Hospital
  • Hôpital Arnaud De Villeneuve
  • University of Sheffield
  • Imperial College London
  • Mayo Clinic
  • Temple University Health System
  • University of Glasgow
  • Leiden University Medical Center
  • Ludwig Maximilian University of Munich
  • University of Pretoria
  • London School of Hygiene & Tropical Medicine
  • University of Southampton
  • University of Westminster
  • University of Münster
  • Royal Marsden NHS Foundation Trust
  • Skåne University Hospital
  • Leipzig University
  • Centre Georges François Leclerc
  • University of California Los Angeles
  • University of Tübingen
  • University of Edinburgh
  • University Medical Center Hamburg-Eppendorf
  • Institute of Cancer Research
  • McGill University
  • Tel Aviv University
  • Curtin University
  • Memorial Sloan Kettering Cancer Center
  • University of North Carolina at Chapel Hill
  • Dana–Farber Cancer Institute
  • University of Würzburg
  • University Hospital of Heraklion
  • Rigshospitalet
  • Mount Sinai Hospital
  • University of Kansas Medical Center
  • University of Utah
  • Spanish National Cancer Research Centre
  • National Institutes of Health
  • Pomeranian Medical University
  • Centre Hospitalier de l’Université de Montréal
  • Medical University of Vienna
  • University of Cologne
  • University of Southern California
  • University of Massachusetts Amherst
  • Kuopio University Hospital
  • University of Western Australia
  • University College London
  • Erasmus University Medical Center
  • NorthShore University HealthSystem
  • Institute of Oncology NN Petrov
  • Georgetown University Medical Center
  • National Cancer Centre
  • Guy's and St Thomas' NHS Foundation Trust
  • Peter MacCallum Cancer Centre
  • State Research Institute Centre for Innovative Medicine
  • University of Ulm
  • Aarhus University Hospital
  • Stanford University
  • Seoul National University
  • TU Dresden
  • National University of Ireland, Galway
  • Radboud University Nijmegen Medical Centre
  • Universitaire Ziekenhuizen Leuven
  • Bashkir State University
  • National Centre of Scientific Research Demokritos
  • University of Oslo
  • Odense University Hospital
  • Hong Kong Sanatorium and Hospital
  • Sheba Medical Center
  • Manchester University NHS Foundation Trust
  • University of Hawaii at Manoa
  • Asan Medical Center
  • Soonchunhyang University Hospital
  • Mayo Clinic
  • Centrum Onkologii Instytut
  • German Breast group
  • Macedonian Academy of Sciences and Arts
  • Fred Hutchinson Cancer Research Center
  • University of California, San Diego
  • Nagoya University
  • University of Lyon System
  • Alfred Hospital
  • VU University Medical Center
  • Hospital Monte Naranco
  • National University of Singapore
  • University of Warwick
  • University Health Network
  • Paris 12 Val de Marne University
  • University of New Mexico
  • University of Florence
  • Uppsala University
  • Aalborg Hospital
  • Portuguese Oncology Institute
  • Moffitt Cancer Center
  • Western General Hospital
  • University of Oulu
  • Karolinska University Hospital
  • Carmel Medical Center
  • Hospital Universitario Puerta de Hierro Majadahonda
  • Städtisches Klinikum Karlsruhe
  • National Institute of Environmental Health Sciences
  • National Cancer Institute of Thailand
  • Case Western Reserve University
  • King's College London
  • University of Newcastle Australia
  • The Ohio State University
  • Academia Sinica
  • Great Ormond Street Hospital for Children NHS Foundation Trust
  • University of British Columbia
  • Krebsregister Saarland
  • University Hospital Heidelberg
  • National Human Genome Research Institute
  • BioCruces Health research Institute
  • University of Eastern Finland
  • University Malaya Medical Centre
  • Columbia University
  • Ospedale di Circolo e Fondazione Macchi
  • Latvian Biomedical Research and Study Centre
  • Addenbrooke's Hospital
  • University of Oxford
  • Pontifical Xavierian University
  • Prince of Wales Hospital
  • Beth Israel Deaconess Medical Center
  • Ospedale San Martino
  • Charité
  • Centro di Riferimento Oncologico
  • Churchill Hospital
  • St. Jude Children's Research Hospital
  • University of Porto
  • Royal Women's Hospital
  • Sapienza University of Rome
  • Technical University Munich
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ng.3785

    DOI

    http://dx.doi.org/10.1038/ng.3785

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1092350084

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/29058716


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