Nature Research, Nature Genetics, 5(41), p. 585-590, 2009
DOI: 10.1038/ng.354
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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. Shahana Ahmed1,87, Gilles Thomas2,87, Maya Ghoussaini1,87, Catherine S Healey1,87, Manjeet K Humphreys3,87, Radka Platte1, Jonathan Morrison3, Melanie Maranian1, Karen A Pooley3, Robert Luben4, Diana Eccles5, D Gareth Evans6, Olivia Fletcher7,8, Nichola Johnson7, Isabel dos Santos Silva8, Julian Peto8,9, Michael R Stratton10, Nazneen Rahman11, Kevin Jacobs2,12,13, Ross Prentice14, Garnet L Anderson14, Aleksandar Rajkovic15, J David Curb16, Regina G Ziegler2, Christine D Berg17, Saundra S Buys18, Catherine A McCarty19, Heather Spencer Feigelson20, Eugenia E Calle20, Michael J Thun20, W Ryan Diver20, Stig Bojesen21,22, Børge G Nordestgaard21,22, Henrik Flyger23, Thilo Dörk24, Peter Schürmann24, Peter Hillemanns24, Johann H Karstens25, Natalia V Bogdanova24,25,26, Natalia N Antonenkova26, Iosif V Zalutsky26, Marina Bermisheva24,27, Sardana Fedorova28, Elza Khusnutdinova27, SEARCH1,3, Daehee Kang29, Keun-Young Yoo29, Dong Young Noh29, Sei-Hyun Ahn29, Peter Devilee30,31, Christi J van Asperen32, R A E M Tollenaar33, Caroline Seynaeve34, Montserrat Garcia-Closas2, Jolanta Lissowska35, Louise Brinton36, Beata Peplonska37, Heli Nevanlinna38, Tuomas Heikkinen38, Kristiina Aittomäki39, Carl Blomqvist40, John L Hopper41, Melissa C Southey42, Letitia Smith43, Amanda B Spurdle43, Marjanka K Schmidt44, Annegien Broeks44, Richard R van Hien44, Sten Cornelissen44, Roger L Milne45, Gloria Ribas46, Anna González-Neira47, Javier Benitez46,47, Rita K Schmutzler48, Barbara Burwinkel49,50, Claus R Bartram51, Alfons Meindl52, Hiltrud Brauch53,54, Christina Justenhoven53,54, Ute Hamann55, The GENICA Consortium53,54, Jenny Chang-Claude56, Rebecca Hein56, Shan Wang-Gohrke57, Annika Lindblom58, Sara Margolin59, Arto Mannermaa60,61, Veli-Matti Kosma60,61, Vesa Kataja62,63, Janet E Olson64, Xianshu Wang64, Zachary Fredericksen64, Graham G Giles41,65, Gianluca Severi41,65, Laura Baglietto41,65, Dallas R English41,65, Susan E Hankinson66, David G Cox66, Peter Kraft67, Lars J Vatten68, Kristian Hveem68, Merethe Kumle69, Alice Sigurdson2, Michele Doody2, Parveen Bhatti2, Bruce H Alexander70, Maartje J Hooning71, Ans M W van den Ouweland72, Rogier A Oldenburg72, Mieke Schutte71, Per Hall73, Kamila Czene73, Jianjun Liu74, Yuqing Li74, Angela Cox75, Graeme Elliott75, Ian Brock75, Malcolm W R Reed76, Chen-Yang Shen77,78, Jyh-Cherng Yu79, Giu-Cheng Hsu79, Shou-Tung Chen80, Hoda Anton-Culver81, Argyrios Ziogas81, Irene L Andrulis82,83, Julia A Knight82, kConFab84, Australian Ovarian Cancer Study Group43,84, Jonathan Beesley43, Ellen L Goode64, Fergus Couch64, Georgia Chenevix-Trench43, Robert N Hoover2, Bruce A J Ponder1,85, David J Hunter66,67, Paul D P Pharoah1,3, Alison M Dunning1, Stephen J Chanock86 & Douglas F Easton3