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Genome-wide association analysis identifies three new breast cancer susceptibility loci

2012; Nature Portfolio; Volume: 44; Issue: 3 Linguagem: Inglês

10.1038/ng.1049

1546-1718

Maya Ghoussaini, Olivia Fletcher, Kyriaki Michailidou, Clare Turnbull, Marjanka K. Schmidt, Ed Dicks, Joe Dennis, Qin Wang, Manjeet K. Humphreys, Craig Luccarini, Caroline Baynes, Don Conroy, Melanie Maranian, Shahana Ahmed, Kristy Driver, Nichola Johnson, Nick Orr, Isabel dos‐Santos‐Silva, Quinten Waisfisz, Hanne Meijers‐Heijboer, André G. Uitterlinden, Fernando Rivadeneira, Per Hall, Kamila Czene, Astrid Irwanto, Jianjun Liu, Heli Nevanlinna, Kristiina Aittomäki, Carl Blomqvist, Alfons Meindl, Rita K. Schmutzler, Bertram Müller‐Myhsok, Peter Lichtner, Jenny Chang‐Claude, Rebecca Hein, Stefan Nickels, Dieter Flesch‐Janys, Helen Tsimiklis, Enes Makalic, Daniel F. Schmidt, Minh Bui, John L. Hopper, Carmel Apicella, Daniel J. Park, Melissa C. Southey, David J. Hunter, Stephen J. Chanock, Annegien Broeks, Senno Verhoef, Frans B.L. Hogervorst, Peter A. Fasching, Michael P. Lux, Matthias W. Beckmann, Arif B. Ekici, Elinor J. Sawyer, Ian Tomlinson, Michael J. Kerin, Frederik Marmé, Andreas Schneeweiß, Christof Sohn, Barbara Burwinkel, Pascal Guénel, Thérèse Truong, Emilie Cordina‐Duverger, F. Ménégaux, Stig E. Bojesen, Børge G. Nordestgaard, Sune F. Nielsen, Henrik Flyger, Roger L. Milne, M. Rosario Alonso, Anna González‐Neira, Javier Benı́tez, Hoda Anton‐Culver, Argyrios Ziogas, Leslie Bernstein, Christina Clarke Dur, Hermann Brenner, Heiko Müller, Volker Arndt, Christa Stegmaier, Christina Justenhoven, Hiltrud Brauch, Thomas Brüning, Shan Wang‐Gohrke, Ursula Eilber, Thilo Dörk, Peter Schürmann, Michael Bremer, Peter Hillemanns, Natalia Bogdanova, Natalia Antonenkova, Yuriy Rogov, Johann H. Karstens, Marina Bermisheva, Darya Prokofieva, Э. К. Хуснутдинова, Annika Lindblom, Sara Margolin, Graham J. Mann, Vesa Kataja, Veli‐Matti Kosma, Jaana M. Hartikainen, Diether Lambrechts, Betül T. Yesilyurt, Giuseppe Floris, Karin Leunen, Siranoush Manoukian, Bernardo Bonanni, Stefano Fortuzzi, Paolo Peterlongo, Fergus J. Couch, Xianshu Wang, Kristen N. Stevens, Adam Lee, Graham G. Giles, Laura Baglietto, Gianluca Severi, Catriona McLean, Grethe Grenaker Alnæs, Vessela N. Kristensen, Anne-Lise Børrensen-Dale, Esther M. John, Alexander Miron, Robert Winqvist, Katri Pylkäs, Arja Jukkola‐Vuorinen, Saila Kauppila, Irene L. Andrulis, Gord Glendon, Anna Marie Mulligan, Peter Devilee, C. J. van Asperen, Rob A.�E.�M. Tollenaar, Caroline Seynaeve, Jonine D. Figueroa, Montserrat García‐Closas, Louise A. Brinton, Jolanta Lissowska, Maartje J. Hooning, Antoinette Hollestelle, Rogier A. Oldenburg, Ans M.W. van den Ouweland, Angela Cox, Malcolm Reed, Mitul Shah, Anna Jakubowska, Jan Lubiński, Katarzyna Jaworska, Katarzyna Durda, Michael E. Jones, Minouk J. Schoemaker, Alan Ashworth, Anthony J. Swerdlow, Jonathan Beesley, Xiaohong Chen, Kenneth Muir, Artitaya Lophatananon, Suthee Rattanamongkongul, Arkom Chaiwerawattana, Daehee Kang, Keun-Young Yoo, Dong‐Young Noh, Chen‐Yang Shen, Jyh‐Cherng Yu, Pei‐Ei Wu, Chia‐Ni Hsiung, Annie Perkins, Ruth Swann, Louiza S. Velentzis, Diana Eccles, William Tapper, Susan M. Gerty, Nikki Graham, Bruce A.J. Ponder, Georgia Chenevix‐Trench, Paul D.P. Pharoah, Mark Lathrop, Alison M. Dunning, Nazneen Rahman, Julian Peto, Douglas F. Easton,

Genetic factors in colorectal cancer

Breast cancer is the most common cancer among women. To date, 22 common breast cancer susceptibility loci have been identified accounting for ∼8% of the heritability of the disease. We attempted to replicate 72 promising associations from two independent genome-wide association studies (GWAS) in ∼70,000 cases and ∼68,000 controls from 41 case-control studies and 9 breast cancer GWAS. We identified three new breast cancer risk loci at 12p11 (rs10771399; P = 2.7 × 10(-35)), 12q24 (rs1292011; P = 4.3 × 10(-19)) and 21q21 (rs2823093; P = 1.1 × 10(-12)). rs10771399 was associated with similar relative risks for both estrogen receptor (ER)-negative and ER-positive breast cancer, whereas the other two loci were associated only with ER-positive disease. Two of the loci lie in regions that contain strong plausible candidate genes: PTHLH (12p11) has a crucial role in mammary gland development and the establishment of bone metastasis in breast cancer, and NRIP1 (21q21) encodes an ER cofactor and has a role in the regulation of breast cancer cell growth.