Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/37294
Title: Genome-wide association study in BRCA1 mutation carriers identifies novel loci associated with breast and ovarian cancer risk.
Authors: Couch, F. J.
Wang, X.
McGuffog, L.
Lee, A.
Olswold, C.
Kuchenbaecker, K. B.
Soucy, P.
Fredericksen, Z.
Barrowdale, D.
Dennis, J.
Gaudet, M. M.
Dicks, E.
Kosel, M.
Healey, S.
Sinilnikova, O. M.
Lee, A.
Bacot, F.
Vincent, D.
Hogervorst, F. B.
Peock, S.
Stoppa-Lyonnet, D.
Jakubowska, A.
kConFab Investigators
Radice, P.
Schmutzler, R. K.
SWE-BRCA
Domchek, S. M.
Piedmonte, M.
Singer, C. F.
Friedman, E.
Thomassen, M.
Ontario Cancer Genetics Network
Hansen, T. V.
Neuhausen, S. L.
Szabo, C. I.
Blanco, I.
Greene, M. H.
Karlan, B. Y.
Garber, J.
Phelan, C. M.
Weitzel, J. N.
Montagna, M.
Olah, E.
Andrulis, I. L.
Godwin, A. K.
Yannoukakos, D.
Goldgar, D. E.
Caldes, T.
Nevanlinna, H.
Osorio, A.
Terry, M. B.
Daly, M. B.
van Rensburg, E. J.
Hamann, U.
Ramus, S. J.
Toland, A. E.
Caligo, M. A.
Olopade, O. I.
Tung, N.
Claes, K.
Beattie, M. S.
Southey, M. C.
Imyanitov, E. N.
Tischkowitz, M.
Janavicius, R.
John, E. M.
Kwong, A.
Diez, O.
Balmaña, J.
Barkardottir, R. B.
Arun, B. K.
Rennert, G.
Teo, S. H.
Ganz, P. A.
Campbell, I.
van der Hout, A. H.
van Deurzen, C. H.
Seynaeve, C.
Gómez Garcia, E. B.
van Leeuwen, F. E.
Meijers-Heijboer, H. E.
Gille, J. J.
Ausems, M. G.
Blok, M. J.
Ligtenberg, M. J.
Rookus, M. A.
Devilee, P.
Verhoef, S.
van Os, T. A.
Wijnen, J. T.
HEBON
EMBRACE
Frost, D.
Ellis, S.
Fineberg, E.
Platte, R.
Evans, D. G.
Izatt, L.
Eeles, R. A.
Adlard, J.
Eccles, D. M.
Cook, J.
Brewer, C.
Douglas, F.
Hodgson, S.
Morrison, P. J.
Side, L. E.
Donaldson, A.
Houghton, C.
Rogers, M. T.
Dorkins, H.
Eason, J.
Gregory, H.
McCann, E.
Murray, A.
Calender, A.
Hardouin, A.
Berthet, P.
Delnatte, C.
Nogues, C.
Lasset, C.
Houdayer, C.
Leroux, D.
Rouleau, E.
Prieur, F.
Damiola, F.
Sobol, H.
Coupier, I.
Venat-Bouvet, L.
Castera, L.
Gauthier-Villars, M.
Léoné, M.
Pujol, P.
Mazoyer, S.
Bignon, Y. J.
GEMO Study Collaborators
Złowocka-Perłowska, E.
Gronwald, J.
Lubinski, J.
Durda, K.
Jaworska, K.
Huzarski, T.
Spurdle, A. B.
Viel, A.
Peissel, B.
Bonanni, B.
Melloni, G.
Ottini, L.
Papi, L.
Varesco, L.
Tibiletti, M. G.
Peterlongo, P.
Volorio, S.
Manoukian, S.
Pensotti, V.
Arnold, N.
Engel, C.
Deissler, H.
Gadzicki, D.
Gehrig, A.
Kast, K.
Rhiem, K.
Meindl, A.
Niederacher, D.
Ditsch, N.
Plendl, H.
Preisler-Adams, S.
Engert, S.
Sutter, C.
Varon-Mateeva, R.
Wappenschmidt, B.
Weber, B. H.
Arver, B.
Stenmark-Askmalm, M.
Loman, N.
Rosenquist, R.
Einbeigi, Z.
Nathanson, K. L.
Rebbeck, T. R.
Blank, S. V.
Cohn, D. E.
Rodriguez, G. C.
Small, L.
Friedlander, M.
Bae-Jump, V. L.
Fink-Retter, A.
Rappaport, C.
Gschwantler-Kaulich, D.
Pfeiler, G.
Tea, M. K.
Lindor, N. M.
Kaufman, B.
Shimon Paluch, S.
Laitman, Y.
Skytte, A. B.
Gerdes, A. M.
Pedersen, I. S.
Moeller, S. T.
Kruse, T. A.
Jensen, U. B.
Vijai, J.
Sarrel, K.
Robson, M.
Kauff, N.
Mulligan, A. M.
Glendon, G.
Ozcelik, H.
Ejlertsen, B.
Nielsen, F. C.
Jønson, L.
Andersen, M. K.
Ding, Y. C.
Steele, L.
Foretova, L.
Teulé, A.
Lazaro, C.
Brunet, J.
Pujana, M. A.
Mai, P. L.
Loud, J. T.
Walsh, C.
Lester, J.
Orsulic, S.
Narod, S. A.
Herzog, J.
Sand, S. R.
Tognazzo, S.
Agata, S.
Vaszko, T.
Weaver, J.
Stavropoulou, A. V.
Buys, S. S.
Romero, A.
de la Hoya, M.
Aittomäki, K.
Muranen, T. A.
Duran, M.
Chung, W. K.
Lasa, A.
Dorfling, C. M.
Miron, A.
BCFR
Benitez, J.
Senter, L.
Huo, D.
Chan, S. B.
Sokolenko, A. P.
Chiquette, J.
Tihomirova, L.
Friebel, T. M.
Agnarsson, B. A.
Lu, K. H.
Lejbkowicz, F.
James, P. A.
Hall, P.
Dunning, A. M.
Tessier, D.
Cunningham, J.
Slager, S. L.
Wang, C.
Hart, S.
Stevens, K.
Simard, J.
Pastinen, T.
Pankratz, V. S.
Offit, K.
Easton, D. F.
Chenevix-Trench, G.
Antoniou, A. C.
CIMBA
First Published: 27-Mar-2013
Publisher: Public Library of Science
Citation: PLoS Genetics, 2013, 9 (3), e1003212
Abstract: 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(-8), 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(-8), HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4 × 10(-8), 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(-4)). 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.
DOI Link: 10.1371/journal.pgen.1003212
ISSN: 1553-7390
eISSN: 1553-7404
Links: http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1003212
http://hdl.handle.net/2381/37294
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © 2013 Couch et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Appears in Collections:Published Articles, Dept. of Cancer Studies and Molecular Medicine



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