Genome-wide association study identifies novel breast cancer susceptibility loci.
Genome-wide association study identifies novel breast cancer susceptibility loci.
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DOI：
10.1038/nature05887
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发表时间：
2007-06-28
期刊：
影响因子：
64.8
通讯作者：
Ponder, Bruce A. J.
中科院分区：
文献类型：
--
作者：
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;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, Borge 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;Schuermann, Peter;Doerk, 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;Brauch, Hiltrud;Hamann, Ute;Ko, Yon-Dschun;Spurdle, Amanda B.;Beesley, Jonathan;Chen, Xiaoqing;Mannermaa, Arto;Kosma, Veli-Matti;Kataja, Vesa;Hartikainen, Jaana;Day, Nicholas E.;Cox, David R.;Ponder, Bruce A. J.
乳腺癌表现出家族聚集性，与疾病遗传易感性的差异一致。已知的易感基因占乳腺癌家族风险的不到25%，残留的遗传变异可能是由于赋予更多中等风险的变异所致。为了进一步确定易感等位基因，我们在4398例乳腺癌患者和4316名对照中进行了两阶段的全基因组关联研究，随后在第三阶段中，对22项研究中的21,860名病例和22,578名对照进行了30个单核苷酸多态(SNPs)的确认。在R2>；0.5中，我们使用了227,876个SNP，这些SNP估计与欧洲人中77%的已知常见SNPs相关。5个新的独立基因座上的SNP显示出与乳腺癌相关的强有力且一致的证据(P<；10−7)。其中四个含有可信的致病基因(FGFR2、TNRC9、MAP3K1和LSP1)。在第二阶段，1,792个SNP在P<；0.05水平上显著高于估计的1,343个SNPs，这表明通过这种方法可以识别出许多额外的常见易感等位基因。
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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影响因子：
30.8
作者：
de Bakker, PIW;Yelensky, R;Altshuler, D
通讯作者：
Altshuler, D
影响因子：
56.9
作者：
Hinds, DA;Stuve, LL;Cox, DR
通讯作者：
Cox, DR
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64.8
作者：
Erkko, Hannele;Xia, Bing;Winqvist, Robert
通讯作者：
Winqvist, Robert
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14.9
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Clamp, M
人类癌基因组中体细胞突变的模式。
影响因子：
64.8
作者：
Greenman, Christopher;Stephens, Philip;Smith, Raffaella;Dalgliesh, Gillian L.;Hunter, Christopher;Bignell, Graham;Davies, Helen;Teague, Jon;Butler, Adam;Edkins, Sarah;O'Meara, Sarah;Vastrik, Imre;Schmidt, Esther E.;Avis, Tim;Barthorpe, Syd;Bhamra, Gurpreet;Buck, Gemma;Choudhury, Bhudipa;Clements, Jody;Cole, Jennifer;Dicks, Ed;Forbes, Simon;Gray, Kris;Halliday, Kelly;Harrison, Rachel;Hills, Katy;Hinton, Jon;Jenkinson, Andy;Jones, David;Menzies, Andy;Mironenko, Tatiana;Perry, Janet;Raine, Keiran;Richardson, Dave;Shepherd, Rebecca;Small, Alexandra;Tofts, Calli;Varian, Jennifer;Webb, Tony;West, Sofie;Widaa, Sara;Yates, Andy;Cahill, Daniel P.;Louis, David N.;Goldstraw, Peter;Nicholson, Andrew G.;Brasseur, Francis;Looijenga, Leendert;Weber, Barbara L.;Chiew, Yoke-Eng;deFazio, Anna;Greaves, Mel F.;Green, Anthony R.;Campbell, Peter;Birney, Ewan;Easton, Douglas F.;Chenevix-Trench, Georgia;Tan, Min-Han;Khoo, Sok Kean;Teh, Bin Tean;Yuen, Siu Tsan;Leung, Suet Yi;Wooster, Richard;Futreal, P. Andrew;Stratton, Michael R.
通讯作者：
Stratton, Michael R.