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Large-scale genotyping identifies 41 new loci associated with breast cancer risk

2013; Nature Portfolio; Volume: 45; Issue: 4 Linguagem: Inglês

10.1038/ng.2563

1546-1718

Kyriaki Michailidou, Per Hall, Anna González‐Neira, Maya Ghoussaini, Joe Dennis, Roger L. Milne, Marjanka K. Schmidt, Jenny Chang‐Claude, Stig E. Bojesen, Manjeet K. Bolla, Qin Wang, Ed Dicks, Andrew Lee, Clare Turnbull, Nazneen Rahman, Olivia Fletcher, Julian Peto, Lorna J. Gibson, Isabel dos‐Santos‐Silva, Heli Nevanlinna, Taru Muranen, Kristiina Aittomäki, Carl Blomqvist, Kamila Czene, Astrid Irwanto, Jianjun Liu, Quinten Waisfisz, Hanne Meijers‐Heijboer, Muriel A. Adank, Rob B. van der Luijt, Rebecca Hein, Norbert Dahmen, L. Beckman, Alfons Meindl, Rita K. Schmutzler, Bertram Müller‐Myhsok, Peter Lichtner, John L. Hopper, Melissa C. Southey, Enes Makalic, Daniel F. Schmidt, André G. Uitterlinden, Albert Hofman, David J. Hunter, Stephen J. Chanock, Daniel Vincent, François Bacot, Daniel C. Tessier, Sander Canisius, Lodewyk F.A. Wessels, Christopher A. Haiman, Mitul Shah, Robert Luben, Judith Brown, Craig Luccarini, Nils Schoof, Keith Humphreys, Jingmei Li, Børge G. Nordestgaard, Sune F. Nielsen, Henrik Flyger, Fergus J. Couch, Xianshu Wang, Celine M. Vachon, Kristen N. Stevens, Diether Lambrechts, Matthieu Moisse, Robert Paridaens, Marie‐Rose Christiaens, Anja Rudolph, Stefan Nickels, Dieter Flesch‐Janys, Nichola Johnson, Zoe Aitken, Kirsimari Aaltonen, Tuomas Heikkinen, Annegien Broeks, Laura J. vanʼt Veer, C. Ellen van der Schoot, Pascal Guénel, Thérèse Truong, Pierre Laurent‐Puig, F. Ménégaux, Frederik Marmé, Andreas Schneeweiß, Christof Sohn, Barbara Burwinkel, M. Pilar Zamora, José Ignacio Arias Pérez, Guillermo Pita, M. Rosario Alonso, Angela Cox, Ian W. Brock, Simon S. Cross, Malcolm Reed, Elinor J. Sawyer, Ian Tomlinson, Michael J. Kerin, Nicola Miller, Brian E. Henderson, Fredrick R. Schumacher, Loı̈c Le Marchand, Irene L. Andrulis, Julia A. Knight, Gord Glendon, Anna Marie Mulligan, Annika Lindblom, Sara Margolin, Maartje J. Hooning, Antoinette Hollestelle, Ans M.W. van den Ouweland, Agnes Jager, Minh Bui, Jennifer Stone, Gillian S. Dite, Carmel Apicella, Helen Tsimiklis, Graham G. Giles, Gianluca Severi, Laura Baglietto, Peter A. Fasching, Lothar Haeberle, Arif B. Ekici, Matthias W. Beckmann, Hermann Brenner, Heiko Müller, Volker Arndt, Christa Stegmaier, Anthony J. Swerdlow, Alan Ashworth, Nick Orr, Michael E. Jones, Jonine D. Figueroa, Jolanta Lissowska, Louise A. Brinton, Mark S. Goldberg, France Labrèche, Martine Dumont, Robert Winqvist, Katri Pylkäs, Arja Jukkola‐Vuorinen, Mervi Grip, Hiltrud Brauch, Ute Hamann, Thomas Brüning, Paolo Radice, Paolo Peterlongo, Siranoush Manoukian, Bernardo Bonanni, Peter Devilee, Rob A.�E.�M. Tollenaar, Caroline Seynaeve, Christi J. van Asperen, Anna Jakubowska, Jan Lubiński, Katarzyna Jaworska, Katarzyna Durda, Graham J. Mann, Vesa Kataja, Veli-Matti Kosma, Jaana M. Hartikainen, Natalia Bogdanova, Natalia Antonenkova, Thilo Dörk, Vessela N. Kristensen, Hoda Anton‐Culver, Susan Slager, Amanda E. Toland, Stephen B. Edge, Florentia Fostira, Daehee Kang, Keun-Young Yoo, Dong‐Young Noh, Keitaro Matsuo, Hidemi Ito, Hiroji Iwata, Aiko Sueta, Anna H. Wu, Chiu-Chen Tseng, David Van Den Berg, Daniel O. Stram, Xiao‐Ou Shu, Wei Lu, Yu-Tang Gao, Hui Cai, Soo‐Hwang Teo, Cheng Har Yip, Sze Yee Phuah, Belinda K. Cornes, Mikael Hartman, Hui Miao, Wei Yen Lim, Jen-Hwei Sng, Kenneth Muir, Artitaya Lophatananon, Sarah Stewart‐Brown, Pornthep Siriwanarangsan, Chen‐Yang Shen, Chia-Ni Hsiung, Pei-Ei Wu, Shian-ling Ding, Suleeporn Sangrajrang, Valérie Gaborieau, Paul Brennan, James McKay, William J. Blot, Lisa B. Signorello, Qiuyin Cai, Wei Zheng, Sandra Deming-Halverson, Martha J. Shrubsole, Jirong Long, Jacques Simard, Montserrat García‐Closas, Paul D.P. Pharoah, Georgia Chenevix‐Trench, Alison M. Dunning, Javier Benı́tez, Douglas F. Easton,

Nutrition, Genetics, and Disease

Douglas Easton, Per Hall and colleagues report meta-analyses of genome-wide association studies for breast cancer, including 10,052 cases and 12,575 controls, followed by genotyping using the iCOGS array in an additional 52,675 cases and 49,436 controls from studies within the Breast Cancer Association Consortium (BCAC). They identify 41 loci newly associated with susceptibility to breast cancer. Breast cancer is the most common cancer among women. Common variants at 27 loci have been identified as associated with susceptibility to breast cancer, and these account for ∼9% of the familial risk of the disease. We report here a meta-analysis of 9 genome-wide association studies, including 10,052 breast cancer cases and 12,575 controls of European ancestry, from which we selected 29,807 SNPs for further genotyping. These SNPs were genotyped in 45,290 cases and 41,880 controls of European ancestry from 41 studies in the Breast Cancer Association Consortium (BCAC). The SNPs were genotyped as part of a collaborative genotyping experiment involving four consortia (Collaborative Oncological Gene-environment Study, COGS) and used a custom Illumina iSelect genotyping array, iCOGS, comprising more than 200,000 SNPs. We identified SNPs at 41 new breast cancer susceptibility loci at genome-wide significance (P < 5 × 10−8). Further analyses suggest that more than 1,000 additional loci are involved in breast cancer susceptibility.