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Newly discovered breast cancer susceptibility loci on 3p24 and 17q23.2

2009; Nature Portfolio; Volume: 41; Issue: 5 Linguagem: Inglês

10.1038/ng.354

1546-1718

Shahana Ahmed, Gilles Thomas, Maya Ghoussaini, Catherine S. Healey, Manjeet K. Humphreys, Radka Platte, Jonathan J. Morrison, Melanie Maranian, Karen A. Pooley, Robert Luben, Diana Eccles, D. Gareth Evans, Olivia Fletcher, Nichola Johnson, Isabel dos‐Santos‐Silva, Julian Peto, Michael R. Stratton, Nazneen Rahman, Kevin B. Jacobs, Ross L. Prentice, Garnet L. Anderson, Aleksandar Rajkovic, J. David Curb, Regina G. Ziegler, Christine D. Berg, Saundra S. Buys, Catherine A. McCarty, Heather Spencer Feigelson, Eugenia E. Calle, Michael J. Thun, W. Ryan Diver, Stig E. Bojesen, Børge G. Nordestgaard, Henrik Flyger, Thilo Dörk, Peter Schürmann, Peter Hillemanns, Johann H. Karstens, Natalia Bogdanova, Natalia Antonenkova, Iosif V. Zalutsky, Marina Bermisheva, С.А. Федорова, Э. К. Хуснутдинова, Daehee Kang, Keun-Young Yoo, Dong‐Young Noh, Sei-Hyun Ahn, Peter Devilee, Christi J. van Asperen, Robert A.E.M. Tollenaar, Caroline Seynaeve, Montserrat García‐Closas, Jolanta Lissowska, Louise A. Brinton, Beata Pepłońska, Heli Nevanlinna, Tuomas Heikkinen, Kristiina Aittomäki, Carl Blomqvist, John L. Hopper, Melissa C. Southey, Letitia Smith, Amanda B. Spurdle, Marjanka K. Schmidt, Annegien Broeks, Richard R van Hien, Sten Cornelissen, Roger L. Milne, Glòria Ribas, Anna González‐Neira, Javier Benı́tez, Rita K. Schmutzler, Barbara Burwinkel, Claus R. Bartram, Alfons Meindl, Hiltrud Brauch, Christina Justenhoven, Ute Hamann, Jenny Chang‐Claude, Rebecca Hein, Shan Wang‐Gohrke, Annika Lindblom, Sara Margolin, Graham J. Mann, Veli-Matti Kosma, Vesa Kataja, Janet E. Olson, Xianshu Wang, Zachary Fredericksen, Graham G. Giles, Gianluca Severi, Laura Baglietto, Dallas R. English, Susan E. Hankinson, David G. Cox, Peter Kraft, Lars J. Vatten, Kristian Hveem, Merethe Kumle, Alice J. Sigurdson, Michele M. Doody, Parveen Bhatti, Bruce H. Alexander, Maartje J. Hooning, Ans M.W. van den Ouweland, Rogier A. Oldenburg, Mieke Schutte, Per Hall, Kamila Czene, Jianjun Liu, Yuqing Li, Angela Cox, Graeme Elliott, Ian W. Brock, Malcolm Reed, Chen‐Yang Shen, Jyh-Cherng Yu, Giu-Cheng Hsu, Shou-Tung Chen, Hoda Anton‐Culver, Argyrios Ziogas, Irene L. Andrulis, Julia A. Knight, Jonathan Beesley, Ellen L. Goode, Fergus J. Couch, Georgia Chenevix‐Trench, Robert N. Hoover, Bruce A.J. Ponder, David J. Hunter, Paul D.P. Pharoah, Alison M. Dunning, Stephen J. Chanock, Douglas F. Easton,

Genomics and Chromatin Dynamics

Douglas Easton and colleagues report results of a large multistage genome-wide association study of breast cancer. The study identifies two new breast cancer risk loci on chromosomes 3p24 and 17q23.2. Genome-wide association studies (GWAS) have identified seven breast cancer susceptibility loci, but these explain only a small fraction of the familial risk of the disease. Five of these loci were identified through a two-stage GWAS involving 390 familial cases and 364 controls in the first stage, and 3,990 cases and 3,916 controls in the second stage1. To identify additional loci, we tested over 800 promising associations from this GWAS in a further two stages involving 37,012 cases and 40,069 controls from 33 studies in the CGEMS collaboration and Breast Cancer Association Consortium. We found strong evidence for additional susceptibility loci on 3p (rs4973768: per-allele OR = 1.11, 95% CI = 1.08–1.13, P = 4.1 × 10−23) and 17q (rs6504950: per-allele OR = 0.95, 95% CI = 0.92–0.97, P = 1.4 × 10−8). Potential causative genes include SLC4A7 and NEK10 on 3p and COX11 on 17q.