Genome-wide association study identifies novel breast cancer susceptibility loci by 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, Le Marchand Loic, 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, Schürmann Peter, Dörk 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 André, 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, Brauch Hiltrud, Hamann Ute, Ko Yon-Dschun, Spurdle Amanda B, Beesley Jonathan, Chen Xiaoqing, kConFab, AOCS Management Group, Mannermaa Arto, Kosma Veli-Matti, Kataja Vesa, Hartikainen Jaana, Day Nicholas E, Cox David R, Ponder Bruce A J in Nature (2007).

[PMID: 17529967] PubMed


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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