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Genome-wide association study identifies novel breast cancer susceptibility loci

Easton, Douglas F. and Pooley, Karen A. and Dunning, Alison M. and Pharoah, Paul D. P. and Thompson, Deborah and Ballinger, Dennis G. and Struewing, Jeffery P. and Morrison, Jonathan and Field, Helen and Luben, Robert and Wareham, Nicholas and Ahmed, Shahana and Healey, Catherine S. and Bowman, Richard and Meyer, Kerstin B. and Haiman, Christopher A. and Kolonel, Laurence K. and Henderson, Brian E. and Le Marchand, Loic and Brennan, Paul and Sangrajrang, Suleeporn and Gaborieau, Valerie and Odefrey, Fabrice and Shen, Chen-Yang and Wu, Pei-Ei and Wang, Hui-Chun and Eccles, Diana and Evans, D. Gareth and Peto, Julian and Fletcher, Olivia and Johnson, Nichola and Seal, Sheila and Stratton, Michael R. and Rahman, Nazneen and Chenevix-Trench, Georgia and Bojesen, Stig E. and Nordestgaard, Børge G. and Axelsson, Christen K. and Garcia-Closas, Montserrat and Brinton, Louise and Chanock, Stephen and Lissowska, Jolanta and Peplonska, Beata and Nevanlinna, Heli and Fagerholm, Rainer and Eerola, Hannaleena and Kang, Daehee and Yoo, Keun-Young and Noh, Dong-Young and Ahn, Sei-Hyun and Hunter, David J. and Hankinson, Susan E. and Cox, David G. and Hall, Per and Wedren, Sara and Liu, Jianjun and Low, Yen-Ling and Bogdanova, Natalia and Schu¨rmann, Peter and Do¨rk, Do¨rk and Tollenaar, Rob A. E. M. and Jacobi, Catharina E. and Devilee, Peter and Klijn, Jan G. M. and Sigurdson, Alice J. and Doody, Michele M. and Alexander, Bruce H. and Zhang, Jinghui and Cox, Angela and Brock, Ian W. and MacPherson, Gordon and Reed, Malcolm W. R. and Couch, Fergus J. and Goode, Ellen L. and Olson, Janet E. and Meijers-Heijboer, Hanne and van den Ouweland, Ans and Uitterlinden, Andre´ and Rivadeneira, Fernando and Milne, Roger L. and Ribas, Gloria and Gonzalez-Neira, Anna and Benitez, Javier and Hopper, John L. and McCredie, Margaret and Southey, Melissa and Giles, Graham G. and Schroen, Chris and Justenhoven, Christina and Brauch, Hiltrud and Hamann, Ute and Ko, Yon-Dschun and Spurdle, Amanda B. and Beesley, Jonathan and Chen, Xiaoqing and kConFab, _ and the SEARCH, collaborators and AOCS, Management Group and Mannermaa, Arto and Kosma, Veli-Matti and Kataja, Vesa and Hartikainen, Jaana and Day, Nicholas E. and Cox, David R. and Ponder, Bruce A. J. (2007) Genome-wide association study identifies novel breast cancer susceptibility loci. Nature, 447. pp. 1087-1093.

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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,1027). 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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Item Type: Article
Additional Information: Access to full text is subject to the publisher's access restrictions.
Uncontrolled Keywords: Breast cancer, genetic susceptibility, familial risk, plausible causative genes,
Subjects: Health > Public Health > Chronic Illness & Diseases > Cancer
Research
Research > Genetics and Race
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Depositing User: Users 141 not found.
Date Deposited: 02 Apr 2011
Last Modified: 13 May 2011 09:46
Link to this item (URI): http://health-equity.lib.umd.edu/id/eprint/707

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