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Antoniou AC , Spurdle AB , Sinilnikova OM , Healey S , Pooley KA , Schmutzler RK , Versmold B , Engel C , Meindl A , Arnold N , Hofmann W , Sutter C , Niederacher D , Deissler H , Caldes T , Kampjarvi K , Nevanlinna H , Simard J , Beesley J , Chen XQ , Neuhausen SL , Rebbeck TR , Wagner T , Lynch HT , Isaacs C , Weitzel J , Ganz PA , Daly MB , Tomlinson G , Olopade OI , Bium JL , Couch FJ , Peterlongo P , Manoukian S , Barile M , Radice P , Szabo CI , Pereira LHM , Greene MH , Rennert G , Leibkowicz F , Barnett-Griness O , Andrulis IL , Ozcelik H , Gerdes AM , Caligo MA , Laitman Y , Kaufman B , Milgrom R , Friedman E , Domchek SM , Nathanson KL , Osorio A , Llort G , Milne RL , Benitez J , Hamann U , Hogervorst FBL , Manders P , Ligtenberg MJL , van den Ouweland AMW , Peock S , Cook M , Platte R , Evans DG , Eeles R , Pichert G , Chu C , Eccles D , Davidson R , Douglas F , Godwin AK , Barjhoux L , Mazoyer S , Sobol H , Bourdon V , Eisinger F , Chompret A , Capoulade C , Paillerets BBD , Lenoir GM , Gauthier-Villars M , Houdayer C , Stoppa-Lyonnet D , Easton DF
Common breast cancer-predisposition alleles are associated with breast cancer risk in BRCA1 and BRCA2 mutation carriers
American Journal of Human Genetics. 2008 Apr;82(4) :937-948
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Abstract
Germline mutations in BRCA1 and BRCA2 confer high risks of breast cancer. However, evidence suggests that these risks are modified by other genetic or environmental factors that cluster in families. A recent genome-wide association study has shown that common alleles at single nucleotide polymorphisms (SNPs) in FGFR2 (rs2981582), TNRC9 (rs3803662), and MAP3K1 (rs889312) are associated with increased breast cancer risks in the general population. To investigate whether these loci are also associated with breast cancer risk in BRCA1 and BRCA2 mutation carriers, we genotyped these SNPs in a sample of 10,358 mutation carriers from 23 studies. The minor alleles of SNP rs2981582 and rs889312 were each associated with increased breast cancer risk in BRCA2 mutation carriers (per-allele hazard ratio [HR] = 1.32, 95% CI: 1.20-1.45, p(trend) = 1.7 x 10(-8) and HR = 1.12, 95% CI: 1.02-1.24, P-trend = 0.02) but not in BRCA1 carriers. rs3803662 was associated with increased breast canc!
Notes
Antoniou, Antonis C. Spurdle, Amanda B. Sinilnikova, Olga M. Healey, Sue Pooley, Karen A. Schmutzler, Rita K. Versmold, Beatrix Engel, Christoph Meindl, Alfons Arnold, Norbert Hofmann, Wera Sutter, Christian Niederacher, Dieter Deissler, Helmut Caldes, Trinidad Kampjarvi, Kati Nevanlinna, Heli Simard, Jacques Beesley, Jonathan Chen, Xiaoqing Neuhausen, Susan L. Rebbeck, Timothy R. Wagner, Theresa Lynch, Henry T. Isaacs, Claudine Weitzel, Jeffrey Ganz, Patricia A. Daly, Mary B. Tomlinson, Gail Olopade, Olufunmilayo I. Bium, Joanne L. Couch, Fergus J. Peterlongo, Paolo Manoukian, Siranoush Barile, Monica Radice, Paolo Szabo, Csilla I. Pereira, Lutecia H. Mateus Greene, Mark H. Rennert, Gad Leibkowicz, Flavio Barnett-Griness, Ofra Andrulis, Irene L. Ozcelik, Hilmi Gerdes, Anne-Marie Caligo, Maria A. Laitman, Yael Kaufman, Bella Milgrom, Roni Friedman, Eitan Domchek, Susan M. Nathanson, Katherine L. Osorio, Ana Llort, Gemma Milne, Roger L. Benitez, Javier Hamann, Ute Hogervorst, Frans B. L. Manders, Peggy Ligtenberg, Marjolijn J. L. van den Ouweland, Ans M. W. Peock, Susan Cook, Margaret Platte, Radka Evans, D. Gareth Eeles, Rosalind Pichert, Gabriella Chu, Carol Eccles, Diana Davidson, Rosemarie Douglas, Fiona Godwin, Andrew K. Barjhoux, Laure Mazoyer, Sylyie Sobol, Hagay Bourdon, Violaine Eisinger, Francois Chompret, Agnes Capoulade, Corinne Paillerets, Brigitte Bressac-de Lenoir, Gilbert M. Gauthier-Villars, Marion Houdayer, Claude Stoppa-Lyonnet, Dominique Easton, Douglas F. CELL PRESS