Genome-wide association study identifies novel breast cancer susceptibility loci

• Published in: Nature Vol. 447; no. 7148; pp. 1087 - 1093
• Main Authors: Meyer, Kerstin B, Pharoah, Paul D. P, Kataja, Vesa, Haiman, Christopher A, Lissowska, Jolanta, Ko, Yon-Dschun, Hall, Per, Olson, Janet E, Beesley, Jonathan, Zhang, Jinghui, Fagerholm, Rainer, Cox, David G, Meijers-Heijboer, Hanne, Wang, Hui-Chun, Hankinson, Susan E, Field, Helen, Rahman, Nazneen, Le Marchand, Loic, Peplonska, Beata, Gaborieau, Valerie, Hunter, David J, Gonzalez-Neira, Anna, Chenevix-Trench, Georgia, Kang, Daehee, Dörk, Thilo, Jacobi, Catharina E, Bojesen, Stig E, Nordestgaard, Børge G, Alexander, Bruce H, Shen, Chen-Yang, Bogdanova, Natalia, Pooley, Karen A, Brock, Ian W, Goode, Ellen L, Healey, Catherine S, Stratton, Michael R, Cox, David R, Dunning, Alison M, Odefrey, Fabrice, Wu, Pei-Ei, Noh, Dong-Young, Morrison, Jonathan, Bowman, Richard, Cox, Angela, Fletcher, Olivia, Luben, Robert, Couch, Fergus J, Ballinger, Dennis G, Brennan, Paul, Peto, Julian, Tollenaar, Rob A. E. M, Hopper, John L, Easton, Douglas F, Seal, Sheila, Eerola, Hannaleena, Ponder, Bruce A. J, Hartikainen, Jaana, Reed, Malcolm W. R, Klijn, Jan G. M, Wareham, Nicholas, Kosma, Veli-Matti, Low, Yen-Ling, Doody, Michele M, Eccles, Diana, Brinton, Louise, Brauch, Hiltrud, Spurdle, Amanda B, Sigurdson, Alice J, Sangrajrang, Suleeporn, Hamann, Ute, Ahn, Sei-Hyun, Schürmann, Peter, Schroen, Chris, McCredie, Margaret, Evans, D. Gareth, Milne, Roger L, Nevanlinna, Heli, Devilee, Peter, Justenhoven, Christina, Thompson, Deborah, Mannermaa, Arto, Day, Nicholas E, Rivadeneira, Fernando, Kolonel, Laurence K, Benitez, Javier, Ribas, Gloria, Axelsson, Christen K, Giles, Graham G, Yoo, Keun-Young, Chen, Xiaoqing, Southey, Melissa, Uitterlinden, André, Liu, Jianjun, Johnson, Nichola, van den Ouweland, Ans, Chanock, Stephen, MacPherson, Gordon, Henderson, Brian E, Ahmed, Shahana, Wedren, Sara
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 28.06.2007; Nature Publishing Group
• Subjects: Alleles; Apoptosis Regulatory Proteins; Asia, Southeastern; Australia; Biological and medical sciences; Breast; Breast cancer; Breast Neoplasms - genetics; Cancer; Case-Control Studies; Control equipment; Europe - ethnology; Female; Genes; Genetic aspects; Genetic Predisposition to Disease - genetics; Genetic susceptibility; Genetics; Genome, Human - genetics; Genomics; Genotype; Gynecology. Andrology. Obstetrics; High Mobility Group Proteins; Humans; Loci; Mammary gland diseases; MAP Kinase Kinase Kinase 1 - genetics; Medical research; Medical sciences; Medicin och hälsovetenskap; Microfilament Proteins - genetics; North America; Nucleotides; Odds Ratio; Polymorphism; Polymorphism, Single Nucleotide - genetics; Receptor, Fibroblast Growth Factor, Type 2 - genetics; Receptors, Progesterone - genetics; Risk; Risk factors; Trans-Activators; Tumors; United Kingdom; Europe; Asia, Southeastern; Australia; North America; Human; Genetic variability; Genotype; Breast cancer; Malignant tumor; Epidemiology; Mammary gland diseases; Cancerology; Risk factor; Predisposition; Genetics; Single nucleotide polymorphism; Genome; Public health
• ISSN: 0028-0836; 1476-4687; 1476-4687; 1476-4679
• DOI: 10.1038/nature05887

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.