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Genome-wide association study identifies novel breast cancer susceptibility loci. 2007
Douglas F Easton, and
Karen A Pooley, and
Alison M Dunning, and
Paul D P Pharoah, and
Deborah Thompson, and
Dennis G Ballinger, and
Jeffery P Struewing, and
Jonathan Morrison, and
Helen Field, and
Robert Luben, and
Nicholas Wareham, and
Shahana Ahmed, and
Catherine S Healey, and
Richard Bowman, and
, and
Kerstin B Meyer, and
Christopher A Haiman, and
Laurence K Kolonel, and
Brian E Henderson, and
Loic Le Marchand, and
Paul Brennan, and
Suleeporn Sangrajrang, and
Valerie Gaborieau, and
Fabrice Odefrey, and
Chen-Yang Shen, and
Pei-Ei Wu, and
Hui-Chun Wang, and
Diana Eccles, and
D Gareth Evans, and
Julian Peto, and
Olivia Fletcher, and
Nichola Johnson, and
Sheila Seal, and
Michael R Stratton, and
Nazneen Rahman, and
Georgia Chenevix-Trench, and
Stig E Bojesen, and
Børge G Nordestgaard, and
Christen K Axelsson, and
Montserrat Garcia-Closas, and
Louise Brinton, and
Stephen Chanock, and
Jolanta Lissowska, and
Beata Peplonska, and
Heli Nevanlinna, and
Rainer Fagerholm, and
Hannaleena Eerola, and
Daehee Kang, and
Keun-Young Yoo, and
Dong-Young Noh, and
Sei-Hyun Ahn, and
David J Hunter, and
Susan E Hankinson, and
David G Cox, and
Per Hall, and
Sara Wedren, and
Jianjun Liu, and
Yen-Ling Low, and
Natalia Bogdanova, and
Peter Schürmann, and
Thilo Dörk, and
Rob A E M Tollenaar, and
Catharina E Jacobi, and
Peter Devilee, and
Jan G M Klijn, and
Alice J Sigurdson, and
Michele M Doody, and
Bruce H Alexander, and
Jinghui Zhang, and
Angela Cox, and
Ian W Brock, and
Gordon MacPherson, and
Malcolm W R Reed, and
Fergus J Couch, and
Ellen L Goode, and
Janet E Olson, and
Hanne Meijers-Heijboer, and
Ans van den Ouweland, and
André Uitterlinden, and
Fernando Rivadeneira, and
Roger L Milne, and
Gloria Ribas, and
Anna Gonzalez-Neira, and
Javier Benitez, and
John L Hopper, and
Margaret McCredie, and
Melissa Southey, and
Graham G Giles, and
Chris Schroen, and
Christina Justenhoven, and
Hiltrud Brauch, and
Ute Hamann, and
Yon-Dschun Ko, and
Amanda B Spurdle, and
Jonathan Beesley, and
Xiaoqing Chen, and
, and
, and
Arto Mannermaa, and
Veli-Matti Kosma, and
Vesa Kataja, and
Jaana Hartikainen, and
Nicholas E Day, and
David R Cox, and
Bruce A J Ponder
CR-UK Genetic Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK. d.easton@srl.cam.ac.uk
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.
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Keun-Young Yoo, and
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Alice J Sigurdson, and
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Jinghui Zhang, and
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Malcolm W R Reed, and
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Janet E Olson, and
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Ans van den Ouweland, and
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Jonathan Morrison, and
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Robert Luben, and
Nicholas Wareham, and
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Richard Bowman, and
, and
Kerstin B Meyer, and
Christopher A Haiman, and
Laurence K Kolonel, and
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Paul Brennan, and
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Olivia Fletcher, and
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Nazneen Rahman, and
Georgia Chenevix-Trench, and
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Ans van den Ouweland, and
André Uitterlinden, and
Fernando Rivadeneira, and
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Anna Gonzalez-Neira, and
Javier Benitez, and
John L Hopper, and
Margaret McCredie, and
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Chris Schroen, and
Christina Justenhoven, and
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Xiaoqing Chen, and
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Helen Field, and
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Nicholas Wareham, and
Shahana Ahmed, and
Catherine S Healey, and
Richard Bowman, and
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Kerstin B Meyer, and
Christopher A Haiman, and
Laurence K Kolonel, and
Brian E Henderson, and
Loic Le Marchand, and
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Suleeporn Sangrajrang, and
Valerie Gaborieau, and
Fabrice Odefrey, and
Chen-Yang Shen, and
Pei-Ei Wu, and
Hui-Chun Wang, and
Diana Eccles, and
D Gareth Evans, and
Julian Peto, and
Olivia Fletcher, and
Nichola Johnson, and
Sheila Seal, and
Michael R Stratton, and
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Georgia Chenevix-Trench, and
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Børge G Nordestgaard, and
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Montserrat Garcia-Closas, and
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Beata Peplonska, and
Heli Nevanlinna, and
Rainer Fagerholm, and
Hannaleena Eerola, and
Daehee Kang, and
Keun-Young Yoo, and
Dong-Young Noh, and
Sei-Hyun Ahn, and
David J Hunter, and
Susan E Hankinson, and
David G Cox, and
Per Hall, and
Sara Wedren, and
Jianjun Liu, and
Yen-Ling Low, and
Natalia Bogdanova, and
Peter Schürmann, and
Thilo Dörk, and
Rob A E M Tollenaar, and
Catharina E Jacobi, and
Peter Devilee, and
Jan G M Klijn, and
Alice J Sigurdson, and
Michele M Doody, and
Bruce H Alexander, and
Jinghui Zhang, and
Angela Cox, and
Ian W Brock, and
Gordon MacPherson, and
Malcolm W R Reed, and
Fergus J Couch, and
Ellen L Goode, and
Janet E Olson, and
Hanne Meijers-Heijboer, and
Ans van den Ouweland, and
André Uitterlinden, and
Fernando Rivadeneira, and
Roger L Milne, and
Gloria Ribas, and
Anna Gonzalez-Neira, and
Javier Benitez, and
John L Hopper, and
Margaret McCredie, and
Melissa Southey, and
Graham G Giles, and
Chris Schroen, and
Christina Justenhoven, and
Hiltrud Brauch, and
Ute Hamann, and
Yon-Dschun Ko, and
Amanda B Spurdle, and
Jonathan Beesley, and
Xiaoqing Chen, and
, and
, and
Arto Mannermaa, and
Veli-Matti Kosma, and
Vesa Kataja, and
Jaana Hartikainen, and
Nicholas E Day, and
David R Cox, and
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