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, Kerstin B. Meyer, Christopher A. Haiman, Laurence K. Kolonel, Brian E. Henderson, Loic Le Marchand, Paul BrennanSuleeporn 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, Ian W. Brock, 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 Giles, Chris Schroen, Christina Justenhoven, Hiltrud Brauch, Ute Hamann, Yon Dschun Ko, Amanda B. Spurdle, Jonathan Beesley, Xiaoqing Chen, Arto Mannermaa, Veli Matti Kosma, Vesa Kataja, Jaana Hartikainen, Nicholas E. Day, David R. Cox, Bruce A.J. Ponder, Craig Luccarini, Don Conroy, Mitul Shah, Hannah Munday, Clare Jordan, Barbara Perkins, Judy West, Karen Redman, Kristy Driver, Morteza Aghmesheh, David Amor, Lesley Andrews, Yoland Antill, Jane Armes, Shane Armitage, Leanne Arnold, Rosemary Balleine, Glenn Begley, John Beilby, Ian Bennett, Barbara Bennett, Geoffrey Berry, Anneke Blackburn, Meagan Brennan, Melissa Brown, Michael Buckley, Jo Burke, Phyllis Butow, Keith Byron, David Callen, Ian Campbell, Christine Clarke, Alison Colley, Dick Cotton, Jisheng Cui, Bronwyn Culling, Margaret Cummings, Sarah Jane Dawson, Joanne Dixon, Alexander Dobrovic, Tracy Dudding, Ted Edkins, Maurice Eisenbruch, Gelareh Farshid, Susan Fawcett, Michael Field, Frank Firgaira, Jean Fleming, John Forbes, Michael Friedlander, Clara Gaff, Mac Gardner, Mike Gattas, Peter George, Grantley Gill, Jack Goldblatt, Sian Greening, Scott Grist, Eric Haan, Marion Harris, Stewart Hart, Nick Hayward, John Hopper, Evelyn Humphrey, Mark Jenkins, Alison Jones, Rick Kefford, Judy Kirk, James Kollias, Sergey Kovalenko, Sunil Lakhani, Jennifer Leary, Jacqueline Lim, Geoff Lindeman, Lara Lipton, Liz Lobb, Mariette Maclurcan, Graham Mann, Deborah Marsh, Michael McKay, Sue Anne McLachlan, Bettina Meiser, Roger Milne, Gillian Mitchell, Beth Newman, Imelda O'Loughlin, Richard Osborne, Lester Peters, Kelly Phillips, Melanie Price, Jeanne Reeve, Tony Reeve, Robert Richards, Gina Rinehart, Bridget Robinson, Barney Rudzki, Elizabeth Salisbury, Joe Sambrook, Christobel Saunders, Clare Scott, Elizabeth Scott, Rodney Scott, Ram Seshadri, Andrew Shelling, Amanda Spurdle, Graeme Suthers, Donna Taylor, Christopher Tennant, Heather Thorne, Sharron Townshend, Kathy Tucker, Janet Tyler, Deon Venter, Jane Visvader, Ian Walpole, Robin Ward, Paul Waring, Bev Warner, Graham Warren, Elizabeth Watson, Rachael Williams, Judy Wilson, Ingrid Winship, Mary Ann Young, David Bowtell, David Bowtell, Adele Green, Anna DeFazio, Dorota Gertig, Penny Webb

Research output: Contribution to journalArticle

Abstract

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 (US)
Pages (from-to)1087-1093
Number of pages7
JournalNature
Volume447
Issue number7148
DOIs
StatePublished - Jun 28 2007

ASJC Scopus subject areas

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    Easton, D. F., Pooley, K. A., Dunning, A. M., Pharoah, P. D. P., Thompson, D., Ballinger, D. G., Struewing, J. P., Morrison, J., Field, H., Luben, R., Wareham, N., Ahmed, S., Healey, C. S., Bowman, R., Meyer, K. B., Haiman, C. A., Kolonel, L. K., Henderson, B. E., Le Marchand, L., ... Webb, P. (2007). Genome-wide association study identifies novel breast cancer susceptibility loci. Nature, 447(7148), 1087-1093. https://doi.org/10.1038/nature05887