Genome-wide association study identifies novel breast cancer susceptibility loci

Easton, Douglas F., Pooley, Karen A., Dunning, Alison M., Pharoah, Paul D. P., Thompson, Deborah, Ballinger, Dennis G., Struewing, Jeffery P., Morrison, Jonathan, Field, Helen, Luben, Robert, Wareham, Nicholas, Ahmed, Shahana, Healey, Catherine S., Bowman, Richard, SEARCH collaborators, Meyer, Kerstin B., Haiman, Christopher A., Kolonel, Laurence K., Henderson, Brian E., Marchand, Loic Le, Brennan, Paul, Sangrajrang, Suleeporn, Gaborieau, Valerie, Odefrey, Fabrice, Shen, Chen-Yang, Wu, Pei-Ei, Wang, Hui-Chun, Eccles Diana, Evans, D. Gareth, Peto, Julian, Fletcher, Olivia, Johnson, Nichola, Seal, Sheila, Stratton, Michael R., Rahman, Nazneen, Chenevix-Trench, Georgia, Bojesen, Stig E., Nordestgaard, Børge G., Axelsson, Christen K., Garcia-Closas, Montserrat, Brinton, Louise, Chanock, Stephen, Lissowska, Jolanta, Peplonska, Beata, Nevanlinna, Heli, Fagerholm, Rainer, Eerola, Hannaleena, Kang, Daehee, Yoo, Keun-Young, Noh, Dong-Young, Ahn, Sei-Hyun, Hunter, David J., Hankinson, Susan E., Cox, David G., Hall, Per, Wedren, Sara, Liu, Jianjun, Low, Yen-Ling, Bogdanova, Natalia, Schurmann, Peter, Dork, Thilo, Tollenaar, Rob A. E. M., Jacobi, Catharina E., Devilee, Peter, Klijn, Jan G. M., Sigurdson, Alice J., Doody, Michele M., Alexander, Bruce H., Zhang, Jinghui, Cox, Angela, Brock, Ian W., MacPherson, Gordon, Reed, Malcolm W. R., Couch, Fergus J., Goode, Ellen L., Olson, Janet E., Meijers-Heijboer, Hanne, van den Ouweland, Ans, Uitterlinden, Andre´, Rivadeneira, Fernando, Milne, Roger L., Ribas, Gloria, Gonzalez-Neira, Anna, Benitez, Javier, Hopper, John L., McCredie, Margaret, Southey, Melissa, Giles, Graham G., Schroen, Chris, Justenhoven, Christina, kConFab, AOCS Management Group, Mannermaa, Arto, Kosma, Veli-Matti, Kataja, Vesa, Hartikainen, Jaana, Day, Nicholas E., Cox, David R., Ponder, Bruce A. J., Spurdle, Amanda B., Beesley, Jonathan, Brown, Melissa, Cummings, Margaret, Lakhani, Sunil, Armes, Jane and Ward, Robyn (2007) Genome-wide association study identifies novel breast cancer susceptibility loci. Nature, 447 7148: 1087-1093. doi:10.1038/nature05887

Author Easton, Douglas F.
Pooley, Karen A.
Dunning, Alison M.
Pharoah, Paul D. P.
Thompson, Deborah
Ballinger, Dennis G.
Struewing, Jeffery P.
Morrison, Jonathan
Field, Helen
Luben, Robert
Wareham, Nicholas
Ahmed, Shahana
Healey, Catherine S.
Bowman, Richard
SEARCH collaborators
Meyer, Kerstin B.
Haiman, Christopher A.
Kolonel, Laurence K.
Henderson, Brian E.
Marchand, Loic Le
Brennan, Paul
Sangrajrang, Suleeporn
Gaborieau, Valerie
Odefrey, Fabrice
Shen, Chen-Yang
Wu, Pei-Ei
Wang, Hui-Chun
Eccles Diana
Evans, D. Gareth
Peto, Julian
Fletcher, Olivia
Johnson, Nichola
Seal, Sheila
Stratton, Michael R.
Rahman, Nazneen
Chenevix-Trench, Georgia
Bojesen, Stig E.
Nordestgaard, Børge G.
Axelsson, Christen K.
Garcia-Closas, Montserrat
Brinton, Louise
Chanock, Stephen
Lissowska, Jolanta
Peplonska, Beata
Nevanlinna, Heli
Fagerholm, Rainer
Eerola, Hannaleena
Kang, Daehee
Yoo, Keun-Young
Noh, Dong-Young
Ahn, Sei-Hyun
Hunter, David J.
Hankinson, Susan E.
Cox, David G.
Hall, Per
Wedren, Sara
Liu, Jianjun
Low, Yen-Ling
Bogdanova, Natalia
Schurmann, Peter
Dork, Thilo
Tollenaar, Rob A. E. M.
Jacobi, Catharina E.
Devilee, Peter
Klijn, Jan G. M.
Sigurdson, Alice J.
Doody, Michele M.
Alexander, Bruce H.
Zhang, Jinghui
Cox, Angela
Brock, Ian W.
MacPherson, Gordon
Reed, Malcolm W. R.
Couch, Fergus J.
Goode, Ellen L.
Olson, Janet E.
Meijers-Heijboer, Hanne
van den Ouweland, Ans
Uitterlinden, Andre´
Rivadeneira, Fernando
Milne, Roger L.
Ribas, Gloria
Gonzalez-Neira, Anna
Benitez, Javier
Hopper, John L.
McCredie, Margaret
Southey, Melissa
Giles, Graham G.
Schroen, Chris
Justenhoven, Christina
AOCS Management Group
Mannermaa, Arto
Kosma, Veli-Matti
Kataja, Vesa
Hartikainen, Jaana
Day, Nicholas E.
Cox, David R.
Ponder, Bruce A. J.
Spurdle, Amanda B.
Beesley, Jonathan
Brown, Melissa
Cummings, Margaret
Lakhani, Sunil
Armes, Jane
Ward, Robyn
Title Genome-wide association study identifies novel breast cancer susceptibility loci
Journal name Nature   Check publisher's open access policy
ISSN 0028-0836
Publication date 2007-06-28
Sub-type Article (original research)
DOI 10.1038/nature05887
Volume 447
Issue 7148
Start page 1087
End page 1093
Total pages 9
Place of publication London, U.K.
Publisher Nature Publishing Group
Language eng
Subject 0304 Medicinal and Biomolecular Chemistry
1112 Oncology and Carcinogenesis
Formatted 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 r(2) > 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.
Keyword Growth factor receptor 2
Ovarian cancer
Brca2 mutations
Prostate cancer
Q-Index Code C1

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