Genome-wide association study identifies novel breast cancer susceptibility loci

Douglas F. Easton, Karen A. Pooley, Alison M. Dunning, Paul D.P. Pharoah, Deborah Thompson, Dennis G. Ballinger, Jeffery P. Struewing, Jonathan Morrison, Helen Field, Robert Luben, Nicholas Wareham, Shahana Ahmed, Catherine S. Healey, Richard Bowman, The SEARCH Collaborators, Kerstin B. Meyer, Christopher A. Haiman, Laurence K. Kolonel, Brian E. Henderson, Loic Le MarchandPaul Brennan, Suleeporn Sangrajrang, Valerie Gaborieau, Fabrice Odefrey, Chen-Yang Shen, Pei-Ei Wu, Hui-Chun Wang, Diana Eccles, D. Gareth Evans, Julian Peto, Olivia Fletcher, Nichola Johnson, Sheila Seal, Michael R. Stratton, Nazneen Rahman, Georgia Chenevix-Trench, Stig E. Bojesen, Børge G. Nordestgaard, Christen K. Axelsson, Montserrat Garcia-Closas, Louise Brinton, Stephen Chanock, Jolanta Lissowska, Beata Peplonska, Heli Nevanlinna, Rainer Fagerholm, Hannaleena Eerola, Daehee Kang, Keun-Young Yoo, Dong-Young Noh, Sei-Hyun Ahn, David J. Hunter, Susan E. Hankinson, David G. Cox, Per Hall, Sara Wedren, Jianjun Liu, Yen-Ling Low, Natalia Bogdanova, Peter Schürmann, Thilo Dörk, Rob A.E.M. Tollenaar, Catharina E. Jacobi, Peter Devilee, Jan G.M. Klijn, Alice J. Sigurdson, Michele M. Doody, Bruce H. Alexander, Jinghui Zhang, Angela Cox, Gordon MacPherson, Malcolm W.R. Reed, Fergus J. Couch, Ellen L. Goode, Janet E. Olson, Hanne Meijers-Heijboer, Ans Van Den Ouweland, André Uitterlinden, Fernando Rivadeneira, Roger L. Milne, Gloria Ribas, Anna Gonzalez-Neira, Javier Benitez, John L. Hopper, Margaret McCredie, Melissa Southey, Graham G. Giles, Chris Schroen, Christina Justenhoven, Hiltrud Brauch, Ute Hamann, Yon-Dschun Ko, Amanda B. Spurdle, Jonathan Beesley, Xiaoqing Chen, kConFab, AOCS Management Group, Arto Mannermaa, Veli Matti Kosma, Vesa Kataja, Jaana Hartikainen, Nicholas E. Day, David R. Cox, Bruce A.J. Ponder, Frank Firgaira, Scott Grist, Eric Haan, Ram Seshadri

Research output: Contribution to journalArticlepeer-review

1849 Citations (Scopus)


Breast cancer exhibits familial aggregation, consistent with variation in genetic susceptibility to the disease. Known susceptibility genes account for less than 25% of the familial risk of breast cancer, and the residual genetic variance is likely to be due to variants conferring more moderate risks. To identify further susceptibility alleles, we conducted a two-stage genome-wide association study in 4,398 breast cancer cases and 4,316 controls, followed by a third stage in which 30 single nucleotide polymorphisms (SNPs) were tested for confirmation in 21,860 cases and 22,578 controls from 22 studies. We used 227,876 SNPs that were estimated to correlate with 77% of known common SNPs in Europeans at r2> 0.5. SNPs in five novel independent loci exhibited strong and consistent evidence of association with breast cancer (P < 10-7). Four of these contain plausible causative genes (FGFR2, TNRC9, MAP3K1 and LSP1). At the second stage, 1,792 SNPs were significant at the P < 0.05 level compared with an estimated 1,343 that would be expected by chance, indicating that many additional common susceptibility alleles may be identifiable by this approach.

Original languageEnglish
Pages (from-to)1087-1093
Number of pages7
Publication statusPublished - 28 Jun 2007
Externally publishedYes


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