2026-04-17T20:02:09Zhttps://recercat.cat/oai/request

oai:recercat.cat:2072/4787562025-10-27T12:46:12Zcom_2072_98col_2072_378192

00925njm 22002777a 4500 dc Couch, Ferguson J. author Wang, Xianshu author McGuffog, Lesley author Lee, Andrew J. author Olswold, Curtis L. author Kuchenbaecker, Karoline author Soucy, Penny author Fredericksen, Z. author Barrowdale, Daniel author Dennis, Joe G. author Gaudet, Mia M. author Dicks, Ed M. author Kosel, Matthew L. author Healey, Sue C. author Sinilnikova, Olga M. author Lee, Adam M. author Bacot, François author Vincent, Daniel author Hogervorst, Frans B. L. author Peock, Susan author Stoppa-Lyonnet, Dominique author Jakubowska, Anna author Radice, Paolo author Schmutzler, Rita Katharina author Domchek, Susan M. author Piedmonte, Marion R. author Singer, Christian Fridolin author Friedman, Eitan A. author Thomassen, Mads author Hansen, Thomas Van Overeem author Neuhausen, Susan L. author Szabo, Csilla I. author Blanco Guillermo, Ignacio author Greene, Mark H. author Karlan, Beth Y. author Garber, Judy Ellen author Phelan, Catherine M. author Weitzel, Jeffrey author Montagna, Marco author Olah, Edith author Andrulis, Irene L. L. author Godwin, Andrew K. author Yannoukakos, Drakoulis author Goldgar, David E. author Caldes, Trinidad author Nevanlinna, Heli A. author Osorio, Ana author Terry, Mary Beth Eth author Daly, Mary Beryl author van Rensburg, Elizabeth J. author Hamann, Ute author Ramus, Susan author Ewart Toland, Amanda author Caligo, Maria author Olopade, Olufunmilayo Ibironke author Tung, Nadine M. author Claes, Kathleen B. M. author Beattie, Mary Spanos author Southey, Melissa author Imyanitov, Evgeny N. author Tischkowitz, Marc D. author Janavicius, Ramūnas author John, Esther M. author Kwong, Ava author Diez, Orland author Balmaña Gelpí, Judith author Barkardottir, Rósa Björk author Arun, Banu K. author Rennert, Gad author Teo, Soo author Ganz, Patricia author Campbell, Ian author van der Hout, Annemarie H. author van Deurzen, Carolien H. M. author Seynaeve, Caroline M. author Gómez Garcia, Encarna B. author van Leeuwen, Flora Elizabeth author Meijers-Heijboer, Hanne E. J. author Gille, Johan author Ausems, Margreet G. E. M. author Blok, Marinus J. author Ligtenberg, Marjolijn J. L. author Rookus, Matti A. author Devilee, Peter P. author Verhoef, Senno author van Os, Theo A. M. author Wijnen, Juul Th. author Frost, Debra author Ellis, Steve D. author Fineberg, Elena author Platte, Radka author Evans, Gareth author Izatt, Louise author Eeles, Rosalind A. author Adlard, Julian author Eccles, Diana M author Cook, Jacqueline A. author Brewer, Carole M. author Douglas, Fiona S. author Hodgson, Shirley Victoria author Morrison, Pattrick author Side, Lucy E. author Donaldson, Alan author Houghton, Catherine author Rogers, Mark T. author Dorkins, Huw R. author Eason, Jacqueline author Gregory, Helen author McCann, Emma author Murray, Alex J. author Calender, Alain author Hardouin, Agnès author Berthet, Pascaline author Delnatte, Capucine author Nogues, Catherine author Lasset, Christine author Houdayer, Claude author Leroux, Dominique author Rouleau, Étienne L. author Prieur, Fabienne author Damiola, F. author Sobol, H. author Coupier, I. author Venat-Bouvet, L. author Castera, L. author Gauthier-Villars, M. author Léoné, M. author Pujol, P. author Mazoyer, S. author Bignon, Y.J. author Złowocka-Perłowska, E. author Gronwald, J. author Lubinski, J. author Durda, K. author Jaworska, K. author Huzarski, T. author Spurdle, A.B. author Peissel, B. author Bonanni, B. author Melloni, G. author Ottini, L. author Papi, L. author Varesco, L. author Tibiletti, M.G. author Peterlongo, P. author Volorio, S. author Manoukian, S. author Pensotti, V. author Arnold, N. author Engel, C. author Deissler, H. author Gadzicki, D. author Gehrig, A. author Kast, K. author Rhiem, K. author Meindl, A. author Niederacher, D. author Ditsch, N. author Plendl, H. author Preisler-Adams, S. author Engert, S. author Sutter, C. author Varon-Mateeva, R. author Wappenschmidt, B. author Weber, B.H.F. author Arver, B. author Stenmark-Askmalm, M. author Loman, N. author Rosenquist, R. author Einbeigi, Z. author Nathanson, K.L. author Rebbeck, T.R. author Blank, S.V. author Cohn, D.E. author Rodriguez, G.C. author Small, L. author Friedlander, M. author Bae-Jump, V.L. author Fink-Retter, A. author Rappaport, C. author Gschwantler-Kaulich, D. author Pfeiler, G. author Tea, M.K. author Lindor, N.M. author Kaufman, B. author Shimon Paluch, S. author Laitman, Y. author Skytte, A.B. author Gerdes, A.M. author Pedersen, I.S. author Moeller, S.T. author Kruse, T.A. author Jensen, U.B. author Vijai, J. author Sarrel, K. author Robson, M. author Kauff, N. author Mulligan, A.M. author Glendon, G. author Ozcelik, H. author Ejlertsen, B. author Nielsen, F.C. author Jønson, L. author Andersen, M.K. author Ding, Y.C. author Steele, L. author Foretova, L. author Teule, Alex author Lazaro Garcia, Conxi author Brunet, Joan author Pujana, Miguel Angel author Mai, P.L. author Loud, J.T. author Walsh, C. author Lester, J. author Orsulic, S. author Narod, Steven A author Herzog, J. author Sand, S.R. author Tognazzo, S. author Agata, Simona author Vaszkó, Tibor author Weaver, J. author Stavropoulou, A.V. author Buys, S.S. author Romero, A. author de la Hoya, M. author Aittomäki, K. author Muranen, T.A. author Duran, M. author Chung, W.K. author Lasa, Adriana author Dorfling, C.M. author Miron, A. author Benitez, J. author Senter, L. author Huo, D. author Chan, S.B. author Sokolenko, A.P. author Chiquette, J. author Tihomirova, L. author Friebel, T.M. author Agnarsson, Bjarni A author Lu, K.H. author Lejbkowicz, F. author James, Paul author Hall, P. author Dunning, A.M. author Tessier, Daniel C author Cunningham, Julie M. author Slager, S.L. author Wang, C. author Hart, S. author Stevens, Kristen author Simard, J. author Pastinen, T. author Pankratz, V.S. author Offit, K. author Easton, D.F. author Chenevix-Trench, G. author Antoniou, A.C. author Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia author 2013 BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7×10, HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4×10, HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4×10, HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific association. The 17q21.31 locus was also associated with ovarian cancer risk in 8,211 BRCA2 carriers (P = 2×10). These loci may lead to an improved understanding of the etiology of breast and ovarian tumors in BRCA1 carriers. Based on the joint distribution of the known BRCA1 breast cancer risk-modifying loci, we estimated that the breast cancer lifetime risks for the 5% of BRCA1 carriers at lowest risk are 28%-50% compared to 81%-100% for the 5% at highest risk. Similarly, based on the known ovarian cancer risk-modifying loci, the 5% of BRCA1 carriers at lowest risk have an estimated lifetime risk of developing ovarian cancer of 28% or lower, whereas the 5% at highest risk will have a risk of 63% or higher. Such differences in risk may have important implications for risk prediction and clinical management for BRCA1 carriers. © 2013 Couch et al. BRCA1 Protein BRCA2 Protein Breast Neoplasms Female Genetic Predisposition to Disease Genome-Wide Association Study Genotype Heterozygote Humans Middle Aged Mutation Ovarian Neoplasms Polymorphism, Single Nucleotide Prognosis Risk Factors Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk