Genome-wide association study in BRCA1 mutation carriers identifies Novel Loci associated with breast and ovarian cancer risk

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dc.contributor.author Couch, Fergus J.
dc.contributor.author Wang, Xianshu
dc.contributor.author McGuffog, Lesley
dc.contributor.author Lee, Andrew
dc.contributor.author Olswold, Curtis
dc.contributor.author Kuchenbaecker, Karoline B.
dc.contributor.author Soucy, Penny
dc.contributor.author Fredericksen, Zachary
dc.contributor.author Barrowdale, Daniel
dc.contributor.author Dennis, Joe
dc.contributor.author Gaudet, Mia M.
dc.contributor.author Dicks, Ed
dc.contributor.author Kosel, Matthew
dc.contributor.author Healey, Sue
dc.contributor.author Sinilnikova, Olga M.
dc.contributor.author Lee, Adam
dc.contributor.author Bacot, Francois
dc.contributor.author Vincent, Daniel
dc.contributor.author Hogervorst, Frans B.L.
dc.contributor.author Peock, Susan
dc.contributor.author Stoppa-Lyonnet, Dominique
dc.contributor.author Jakubowska, Anna
dc.contributor.author kConFab Investigators (Kathleen, Cuningham)
dc.contributor.author Radice, Paolo
dc.contributor.author Schmutzler, Rita Katharina
dc.contributor.author Domchek, Susan M.
dc.contributor.author Piedmonte, Marion
dc.contributor.author Singer, Christian F.
dc.contributor.author Friedman, Eitan
dc.contributor.author Thomassen, Mads
dc.contributor.author Ontario Cancer Genetics Network
dc.contributor.author Hansen, Thomas V.O.
dc.contributor.author Neuhausen, Susan L.
dc.contributor.author Szabo, Csilla I.
dc.contributor.author Blanco, Ignacio
dc.contributor.author Greene, Mark H.
dc.contributor.author Karlan, Beth Y.
dc.contributor.author Garber, Judy
dc.contributor.author Phelan, Catherine M.
dc.contributor.author Weitzel, Jeffrey N.
dc.contributor.author Montagna, Marco
dc.contributor.author Olah, Edith
dc.contributor.author Andrulis, Irene L.
dc.contributor.author Godwin, Andrew K.
dc.contributor.author Yannoukakos, Drakoulis
dc.contributor.author Goldgar, David E.
dc.contributor.author Caldes, Trinidad
dc.contributor.author Nevanlinna, Heli
dc.contributor.author Osorio, Ana
dc.contributor.author Terry, Mary Beth
dc.contributor.author Daly, Mary B.
dc.contributor.author Hamann, Ute
dc.contributor.author Ramus, Susan J.
dc.contributor.author Toland, Amanda Ewart
dc.contributor.author Caligo, Maria A.
dc.contributor.author Olopade, Olufunmilayo I.
dc.contributor.author Tung, Nadine
dc.contributor.author Claes, Kathleen
dc.contributor.author Beattie, Mary S.
dc.contributor.author Southey, Melissa C.
dc.contributor.author Imyanitov, Evgeny N.
dc.contributor.author Tischkowitz, Marc
dc.contributor.author Janavicius, Ramunas
dc.contributor.author John, Esther M.
dc.contributor.author Kwong, Ava
dc.contributor.author Diez, Orland
dc.contributor.author Balmana, Judith
dc.contributor.author Barkardottir, Rosa B.
dc.contributor.author Arun, Banu K.
dc.contributor.author Rennert, Gad
dc.contributor.author Teo, Soo-Hwang
dc.contributor.author Ganz, Patricia A.
dc.contributor.author Campbell, Ian G.
dc.contributor.author Van der Hout, Annemarie H.
dc.contributor.author Van Deurzen, Carolien H.M.
dc.contributor.author Seynaeve, Caroline
dc.contributor.author Gomez Garcia, Encarna B.
dc.contributor.author Van Leeuwen, Flora E.
dc.contributor.author Meijers-Heijboer, Hanne E.J.
dc.contributor.author Gille, Johannes J.P.
dc.contributor.author Ausems, Margreet G.E.M.
dc.contributor.author Blok, Marinus J.
dc.contributor.author Ligtenberg, Marjolijn J.L.
dc.contributor.author Rookus, Matti A.
dc.contributor.author Devilee, Peter
dc.contributor.author Verhoef, Senno
dc.contributor.author Van Os, Theo A.M.
dc.contributor.author Wijnen, Juul T.
dc.contributor.author Frost, Debra
dc.contributor.author Ellis, Steve
dc.contributor.author Fineberg, Elena
dc.contributor.author Platte, Radka
dc.contributor.author Evans, D. Gareth
dc.contributor.author Izatt, Louise
dc.contributor.author Eeles, Rosalind A.
dc.contributor.author Adlard, Julian
dc.contributor.author Eccles, Diana M.
dc.contributor.author Cook, Jackie
dc.contributor.author Brewer, Carole
dc.contributor.author Douglas, Fiona
dc.contributor.author Hodgson, Shirley
dc.contributor.author Morrison, Patrick J.
dc.contributor.author Side, Lucy E.
dc.contributor.author Donaldson, Alan
dc.contributor.author Houghton, Catherine
dc.contributor.author Rogers, Mark T.
dc.contributor.author Dorkins, Huw
dc.contributor.author Eason, Jacqueline
dc.contributor.author Gregory, Helen
dc.contributor.author McCann, Emma
dc.contributor.author Calender, Alain
dc.contributor.author Hardouin, Agnes
dc.contributor.author Berthet, Pascaline
dc.contributor.author Delnatte, Capucine
dc.contributor.author Nogues, Catherine
dc.contributor.author Lasset, Christine
dc.contributor.author Houdayer, Claude
dc.contributor.author Leroux, Dominique
dc.contributor.author Rouleau, Etienne
dc.contributor.author Prieur, Fabienne
dc.contributor.author Damiola, Francesca
dc.contributor.author Sobol, Hagay
dc.contributor.author Coupier, Isabelle
dc.contributor.author Venat-Bouvet, Laurence
dc.contributor.author Castera, Laurent
dc.contributor.author Gauthier-Villars, Marion
dc.contributor.author Leone, Melanie
dc.contributor.author Pujol, Pascal
dc.contributor.author Mazoyer, Sylvie
dc.contributor.author Bignon, Yves-Jean
dc.contributor.author Złowocka-Perlowska, Elz bieta
dc.contributor.author Gronwald, Jacek
dc.contributor.author Lubinski, Jan
dc.contributor.author Durda, Katarzyna
dc.contributor.author Jaworska, Katarzyna
dc.contributor.author Huzarski, Tomasz
dc.contributor.author Spurdle, Amanda B.
dc.contributor.author Viel, Alessandra
dc.contributor.author Peissel, Bernard
dc.contributor.author Bonanni, Bernardo
dc.contributor.author Melloni, Giulia
dc.contributor.author Ottini, Laura
dc.contributor.author Papi, Laura
dc.contributor.author Varesco, Liliana
dc.contributor.author Tibiletti, Maria Grazia
dc.contributor.author Peterlongo, Paolo
dc.contributor.author Volorio, Sara
dc.contributor.author Manoukian, Siranoush
dc.contributor.author Pensotti, Valeria
dc.contributor.author Arnold, Norbert
dc.contributor.author Engel, Christoph
dc.contributor.author Deissler, Helmut
dc.contributor.author Gadzicki, Dorothea
dc.contributor.author Gehrig, Andrea
dc.contributor.author Kast, Karin
dc.contributor.author Rhiem, Kerstin
dc.contributor.author Meindl, Alfons
dc.contributor.author Niederacher, Dieter
dc.contributor.author Ditsch, Nina
dc.contributor.author Plendl, Hansjoerg
dc.contributor.author Preisler-Adams, Sabine
dc.contributor.author Engert, Stefanie
dc.contributor.author Sutter, Christian
dc.contributor.author Varon-Mateeva, Raymonda
dc.contributor.author Wappenschmidt, Barbara
dc.contributor.author Weber, Bernhard H.F
dc.contributor.author Arver, Brita
dc.contributor.author Stenmark-Askmalm, Marie
dc.contributor.author Loman, Niklas
dc.contributor.author Rosenquist, Richard
dc.contributor.author Einbeigi, Zakaria
dc.contributor.author Nathanson, Katherine L.
dc.contributor.author Rebbeck, Timothy R.
dc.contributor.author Blank, Stephanie V.
dc.contributor.author Cohn, David E.
dc.contributor.author Rodriguez, Gustavo C.
dc.contributor.author Small, Laurie
dc.contributor.author Friedlander, Michael
dc.contributor.author Bae-Jump, Victoria L.
dc.contributor.author Fink-Retter, Anneliese
dc.contributor.author Rappaport, Christine
dc.contributor.author Gschwantler-Kaulich, Daphne
dc.contributor.author Pfeiler, Georg
dc.contributor.author Tea, Muy-Kheng M.
dc.contributor.author Lindor, Noralane M.
dc.contributor.author Kaufman, Bella
dc.contributor.author Paluch, Shani Shimon
dc.contributor.author Laitman, Yael
dc.contributor.author Skytte, Anne-Bine
dc.contributor.author Gerdes, Anne-Marie
dc.contributor.author Pedersen, Inge Sokilde
dc.contributor.author Moeller, Sanne Traasdahl
dc.contributor.author Kruse, Torben A.
dc.contributor.author Jensen, Uffe Birk
dc.contributor.author Vijai, Joseph
dc.contributor.author Sarrel, Kara
dc.contributor.author Robson, Mark
dc.contributor.author Kauff, Noah
dc.contributor.author Mulligan, Anna Marie
dc.contributor.author Glendon, Gord
dc.contributor.author Ozcelik, Hilmi
dc.contributor.author Ejlertsen, Bent
dc.contributor.author Nielsen, Finn C.
dc.contributor.author Jonson, Lars
dc.contributor.author Andersen, Mette K.
dc.contributor.author Ding, Yuan Chun
dc.contributor.author Steele, Linda
dc.contributor.author Foretova, Lenka
dc.contributor.author Teule, Alex
dc.contributor.author Lazaro, Conxi
dc.contributor.author Brunet, Joan
dc.contributor.author Pujana, Miquel Angel
dc.contributor.author Mai, Phuong L.
dc.contributor.author Loud, Jennifer T.
dc.contributor.author Walsh, Christine
dc.contributor.author Lester, Jenny
dc.contributor.author Orsulic, Sandra
dc.contributor.author Narod, Steven A.
dc.contributor.author Herzog, Josef
dc.contributor.author Sand, Sharon R.
dc.contributor.author Tognazzo, Silvia
dc.contributor.author Agata, Simona
dc.contributor.author Vaszko, Tibor
dc.contributor.author Weaver, Joellen
dc.contributor.author Stavropoulou, Alexandra V.
dc.contributor.author Buys, Saundra S.
dc.contributor.author Romero, Atocha
dc.contributor.author De la Hoya, Miguel
dc.contributor.author Aittomaki, Kristiina
dc.contributor.author Muranen, Taru A.
dc.contributor.author Duran, Mercedes
dc.contributor.author Chung, Wendy K.
dc.contributor.author Lasa, Adriana
dc.contributor.author Miron, Alexander
dc.contributor.author Benitez, Javier
dc.contributor.author Senter, Leigha
dc.contributor.author Huo, Dezheng
dc.contributor.author Chan, Salina B.
dc.contributor.author Sokolenko, Anna P.
dc.contributor.author Chiquette, Jocelyne
dc.contributor.author Tihomirova, Laima
dc.contributor.author Friebel, Tara M.
dc.contributor.author Agnarsson, Bjarni A.
dc.contributor.author Lu, Karen H.
dc.contributor.author Lejbkowicz, Flavio
dc.contributor.author James, Paul A.
dc.contributor.author Hall, Per
dc.contributor.author Dunning, Alison M.
dc.contributor.author Tessier, Daniel C.
dc.contributor.author Cunningham, J.M. (Julie)
dc.contributor.author Slager, Susan L.
dc.contributor.author Wang, Chen
dc.contributor.author Hart, Steven
dc.contributor.author Stevens, Kristen
dc.contributor.author Simard, Jacques
dc.contributor.author Pastinen, Tomi
dc.contributor.author Pankratz, Vernon S.
dc.contributor.author Offit, Kenneth
dc.contributor.author Easton, Douglas F.
dc.contributor.author Georgia, Chenevix-Trench
dc.contributor.author Antoniou, Antonis C.
dc.contributor.author GEMO Study Collaborators
dc.contributor.author SWE-BRCA (Swedish Breast Cancer Study)
dc.contributor.author Ontario Cancer Genetics Network
dc.contributor.author HEBON (Hereditary Breast and Ovarian Cancer Research Group Netherlands)
dc.contributor.author EMBRACE (Epidemiological Study of Familial Breast Cancer)
dc.contributor.author BCFR (Breast Cancer Family Registry)
dc.contributor.author Murray, Alex
dc.contributor.editor Hunter, Kent W.
dc.contributor.upauthor Dorfling, Cecilia Maria
dc.contributor.upauthor Jansen van Rensburg, Elizabeth
dc.date.accessioned 2013-06-20T11:25:46Z
dc.date.available 2013-06-20T11:25:46Z
dc.date.issued 2013-03-27
dc.description BRCA1 mutation carriers have increased and variable risks of breast and ovarian cancer. To identify modifiers of breast and ovarian cancer risk in this population, a multistage GWAS of 14,351 BRCA1 mutation carriers was performed. Loci 1q32 and TCF7L2 at 10q25.3 were associated with breast cancer risk, and two loci at 4q32.2 and 17q21.31 were associated with ovarian cancer risk. The 4q32.3 ovarian cancer locus was not associated with ovarian cancer risk in the general population or in BRCA2 carriers and is the first indication of a BRCA1-specific risk locus for either breast or ovarian cancer. Furthermore, modeling the influence of these modifiers on cumulative risk of breast and ovarian cancer in BRCA1 mutation carriers for the first time showed that a wide range of individual absolute risks of each cancer can be estimated. These differences suggest that genetic risk modifiers may be incorporated into the clinical management of BRCA1 mutation carriers. en_US
dc.description Conceived and designed the experiments: Fergus J Couch, Douglas F Easton, Georgia Chenevix-Trench, Kenneth Offit, Antonis C Antoniou. Performed the experiments: Fergus J Couch, Julie Cunningham, Xianshu Wang, Curtis Olswold, Matthew Kosel, Adam Lee, Mia M Gaudet, Kenneth Offit, Franc¸ois Bacot, Daniel Vincent, Daniel Tessier. Analyzed the data: Antonis C Antoniou, Karoline B Kuchenbaecker, Lesley McGuffog, Daniel Barrowdale, Andrew Lee, Joe Dennis, Ed Dicks, Vernon S Pankratz, Zachary Fredericksen, Curtis Olswold, Matthew Kosel. Contributed reagents/materials/analysis tools: Penny Soucy, Kristen Stevens, Jacques Simard, Tomi Pastinen, Sue Healey, Olga M Sinilnikova, Andrew Lee. Wrote the manuscript: Fergus J Couch, Douglas F Easton, Antonis C Antoniou. Collected data and samples and provided critical review of the manuscript: Fergus J Couch, Xianshu Wang, Lesley McGuffog, Curtis Olswold, Karoline B Kuchenbaecker, Penny Soucy, Zachary Fredericksen, Daniel Barrowdale, Joe Dennis, Mia M Gaudet, Ed Dicks, Matthew Kosel, Olga M Sinilnikova, Franc¸ois Bacot, Daniel Vincent, Frans BL Hogervorst, Susan Peock, Dominique Stoppa-Lyonnet, Anna Jakubowska, Paolo Radice, Rita Katharina Schmutzler, Susan M Domchek, Marion Piedmonte, Christian F Singer, Thomas v O Hansen, Susan L Neuhausen, Csilla I Szabo, Ignacio Blanco, Mark H Greene, Beth Y Karlan, CatherineM Phelan, Jeffrey NWeitzel, Marco Montagna, Edith Olah, Irene L Andrulis, Andrew K Godwin, Drakoulis Yannoukakos, David E Goldgar, Trinidad Caldes, Heli Nevanlinna, Ana Osorio, Mary Beth Terry, Mary B Daly, Elizabeth J van Rensburg, Ute Hamann, Susan J Ramus, Amanda Ewart Toland, Maria A Caligo, Olufunmilayo I Olopade, Nadine Tung, Kathleen Claes, Mary S Beattie, Melissa C Southey, Evgeny N Imyanitov, Ramunas Janavicius, Esther M John, Ava Kwong, Orland Diez, Rosa B Barkardottir, Banu K Arun, Gad Rennert, Soo-Hwang Teo, Patricia A Ganz, Annemarie H van der Hout, Carolien HM van Deurzen, Encarna B Go´mez Garcia, Flora E van Leeuwen, Hanne EJ Meijers-Heijboer, Johannes JP Gille, Margreet GEM Ausems, Marinus J Blok, Marjolijn JL Ligtenberg, Matti A Rookus, Peter Devilee, Theo AM van Os, Juul T Wijnen, Debra Frost, Radka Platte, D Gareth Evans, Louise Izatt, Rosalind A Eeles, Julian Adlard, Diana M Eccles, Carole Brewer, Patrick J Morrison, Lucy E Side, Alan Donaldson, Mark T Rogers, Jacqueline Eason, Helen Gregory, Emma McCann, Alain Calender, Agne`s Hardouin, Pascaline Berthet, Capucine Delnatte, Catherine Nogues, Dominique Leroux, Etienne Rouleau, Fabienne Prieur, Hagay Sobol, Laurence Venat-Bouvet, Laurent Castera, Marion Gauthier- Villars, Me´lanie Le´one´, Yves-Jean Bignon, Elz_bieta Złowocka-Perłowska, Katarzyna Durda, Katarzyna Jaworska, Tomasz Huzarski, Alessandra Viel, Bernard Peissel, Bernardo Bonanni, Giulia Melloni, Laura Ottini, Laura Papi, Liliana Varesco, Maria Grazia Tibiletti, Valeria Pensotti, Norbert Arnold, Christoph Engel, Dorothea Gadzicki, Andrea Gehrig, Karin Kast, Kerstin Rhiem, Dieter Niederacher, Nina Ditsch, Hansjoerg Plendl, Sabine Preisler-Adams, Raymonda Varon-Mateeva, Barbara Wappenschmidt, Bernhard H F Weber, Brita Arver, Marie Stenmark- Askmalm, Richard Rosenquist, Zakaria Einbeigi, Katherine L Nathanson, Timothy R Rebbeck, Stephanie V Blank, David E Cohn, Gustavo C Rodriguez, Michael Friedlander, Victoria L Bae-Jump, Anneliese Fink- Retter, Christine Rappaport, Daphne Gschwantler Kaulich, Georg Pfeiler, Muy-Kheng Tea, Bella Kaufman, Shani Shimon Paluch, Yael Laitman, Anne-Marie Gerdes, Inge Sokilde Pedersen, Sanne Traasdahl Moeller, Torben A Kruse, Uffe Birk Jensen, Joseph Vijai, Mark Robson, Noah Kauff, Anna Marie Mulligan, Gord Glendon, Hilmi Ozcelik, Bent Ejlertsen, Finn C Nielsen, Lars Jønson, Mette K Andersen, Yuan Chun Ding, Lenka Foretova, Alex Teule´, Miquel Angel Pujana, Phuong L Mai, Jennifer T Loud, Sandra Orsulic, Steven A Narod, Josef Herzog, Sharon R Sand, Silvia Tognazzo, Simona Agata, Tibor Vaszko, Joellen Weaver, Alexandra V Stavropoulou, Saundra S Buys, Atocha Romero, Miguel de la Hoya, Kristiina Aittoma¨ ki, Taru A Muranen, Mercedes Duran, Wendy K Chung, Cecilia M Dorfling, Dezheng Huo, Salina B Chan, Anna P Sokolenko, Laima Tihomirova, Tara M Friebel, Bjarni A Agnarsson, Karen H Lu, Flavio Lejbkowicz, Paul A James, Per Hall, Alison M Dunning, Daniel Tessier, Susan L Slager, Jacques Simard, Tomi Pastinen, Vernon S Pankratz, Kenneth Offit, Douglas F Easton, Georgia Chenevix- Trench, Antonis C Antoniou, Andrew Lee, Adam Lee, Adriana Lasa, Alexander Miron, Caroline Seynaeve, Christian Sutter, Eitan Friedman, Elena Fineberg, Christine Lasset, Amanda B Spurdle, Anne-Bine Skytte, Alfons Meindl, Claude Houdayer, Fiona Douglas Francesca Damiola, Catherine Houghton, Alex Murray, Jan Lubinski, Conxi Lazaro, Christine Walsh, Chen Wang, Jenny Lester, Huw Dorkins, Helmut Deissler, Ian Campbell, Isabelle Coupier, Judith Balman˜a, Joan Brunet, Javier Benitez, Jackie Cook, Jocelyne Chiquette, Judy Garber, Jacek Gronwald, Kara Sarrel, Kristen Stevens, Laurie Small, Leigha Senter, Linda Steele, Mads Thomassen, Marc Tischkowitz, Niklas Loman, Noralane M Lindor, Pascal Pujol, Paolo Peterlongo, Steve Ellis, Stefanie Engert, Sue Healey, Shirley Hodgson, Steven Hart, Sylvie Mazoyer, Siranoush, Manoukian, Senno Verhoef, Sara Volorio. en_US
dc.description.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 = 2.761028, HR = 1.14, 95% CI: 1.09–1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.461028, HR = 1.27, 95% CI: 1.17–1.38) and 4q32.3 (rs4691139, P = 3.461028, 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 = 261024). 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. en_US
dc.description.librarian am2013 en_US
dc.description.sponsorship The study was supported by NIH grant CA128978, an NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), a U.S. Department of Defense Ovarian Cancer Idea award (W81XWH-10-1-0341), grants from the Breast Cancer Research Foundation and the Komen Foundation for the Cure; Cancer Research UK grants C12292/A11174 and C1287/A10118; the European Commission’s Seventh Framework Programme grant agreement 223175 (HEALTH-F2-2009-223175). Breast Cancer Family Registry Studies (BCFR): supported by the National Cancer Institute, National Institutes of Health under RFA # CA-06-503 and through cooperative agreements with members of the Breast Cancer Family Registry (BCFR) and Principal Investigators, including Cancer Care Ontario (U01 CA69467), Cancer Prevention Institute of California (U01 CA69417), Columbia University (U01 CA69398), Fox Chase Cancer Center (U01 CA69631), Huntsman Cancer Institute (U01 CA69446), and University of Melbourne (U01 CA69638). The Australian BCFR was also supported by the National Health and Medical Research Council of Australia, the New South Wales Cancer Council, the Victorian Health Promotion Foundation (Australia), and the Victorian Breast Cancer Research Consortium. Melissa C. Southey is a NHMRC Senior Research Fellow and a Victorian Breast Cancer Research Consortium Group Leader. Carriers at FCCC were also identified with support from National Institutes of Health grants P01 CA16094 and R01 CA22435. The New York BCFR was also supported by National Institutes of Health grants P30 CA13696 and P30 ES009089. The Utah BCFR was also supported by the National Center for Research Resources and the National Center for Advancing Translational Sciences, NIH grant UL1 RR025764, and by Award Number P30 CA042014 from the National Cancer Institute. Baltic Familial Breast Ovarian Cancer Consortium (BFBOCC): BFBOCC is partly supported by Lithuania (BFBOCC-LT), Research Council of Lithuania grant LIG-19/2010, and Hereditary Cancer Association (Paveldimo ve˙zˇio asociacija). Latvia (BFBOCC-LV) is partly supported by LSC grant 10.0010.08 and in part by a grant from the ESF Nr.2009/0220/1DP/1.1.1.2.0/09/APIA/VIAA/016. BRCA-gene mutations and breast cancer in South African women (BMBSA): BMBSA was supported by grants from the Cancer Association of South Africa (CANSA) to Elizabeth J. van Rensburg. Beckman Research Institute of the City of Hope (BRICOH): Susan L. Neuhausen was partially supported by the Morris and Horowitz Families Endowed Professorship. BRICOH was supported by NIH R01CA74415 and NIH P30 CA033752. Copenhagen Breast Cancer Study (CBCS): The CBCS study was supported by the NEYE Foundation. Spanish National Cancer Centre (CNIO): This work was partially supported by Spanish Association against Cancer (AECC08), RTICC 06/0020/1060, FISPI08/1120, Mutua Madrilen˜ a Foundation (FMMA) and SAF2010-20493. City of Hope Cancer Center (COH): The City of Hope Clinical Cancer Genetics Community Research Network is supported by Award Number RC4A153828 (PI: Jeffrey N. Weitzel) from the National Cancer Institute and the Office of the Director, National Institutes of Health. CONsorzio Studi ITaliani sui Tumori Ereditari Alla Mammella (CONSIT TEAM): CONSIT TEAM was funded by grants from Fondazione Italiana per la Ricerca sul Cancro (Special Project ‘‘Hereditary tumors’’), Italian Association for Cancer Research (AIRC, IG 8713), Italian Minitry of Health (Extraordinary National Cancer Program 2006, ‘‘Alleanza contro il Cancro’’ and ‘‘Progetto Tumori Femminili), Italian Ministry of Education, University and Research (Prin 2008) Centro di Ascolto Donne Operate al Seno (CAOS) association and by funds from Italian citizens who allocated the 561000 share of their tax payment in support of the Fondazione IRCCS Istituto Nazionale Tumori, according to Italian laws (INT-Institutional strategic projects ‘561000’). German Cancer Research Center (DKFZ): The DKFZ study was supported by the DKFZ. The Hereditary Breast and Ovarian Cancer Research Group Netherlands (HEBON): HEBON is supported by the Dutch Cancer Society grants NKI1998-1854, NKI2004-3088, NKI2007-3756, the NWO grant 91109024, the Pink Ribbon grant 110005, and the BBMRI grant CP46/ NWO. Epidemiological study of BRCA1 & BRCA2 mutation carriers (EMBRACE): EMBRACE is supported by Cancer Research UK Grants C1287/A10118 and C1287/ A11990. D. Gareth Evans and Fiona Lalloo are supported by an NIHR grant to the Biomedical Research Centre, Manchester. The Investigators at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust are supported by an NIHR grant to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. Rosalind A. Eeles and Elizabeth Bancroft are supported by Cancer Research UK Grant C5047/A8385. Fox Chase Cancer Canter (FCCC): The authors acknowledge support from The University of Kansas Cancer Center and the Kansas Bioscience Authority Eminent Scholar Program. Andrew K. Godwin was funded by 5U01CA113916, R01CA140323, and by the Chancellors Distinguished Chair in Biomedical Sciences Professorship. German Consortium of Hereditary Breast and Ovarian Cancer (GC-HBOC): The German Consortium of Hereditary Breast and Ovarian Cancer (GCHBOC) is supported by the German Cancer Aid (grant no 109076, Rita K. Schmutzler) and by the Center for Molecular Medicine Cologne (CMMC). Genetic Modifiers of cancer risk in BRCA1/2 mutation carriers (GEMO): The GEMO study was supported by the Ligue National Contre le Cancer; the Association ‘‘Le cancer du sein, parlons-en!’’ Award and the Canadian Institutes of Health Research for the ‘‘CIHR Team in Familial Risks of Breast Cancer’’ program. Gynecologic Oncology Group (GOG): This study was supported by National Cancer Institute grants to the Gynecologic Oncology Group (GOG) Administrative Office and Tissue Bank (CA 27469), Statistical and Data Center (CA 37517), and GOG’s Cancer Prevention and Control Committtee (CA 101165). Drs. Mark H. Greene and Phuong L. Mai were supported by funding from the Intramural Research Program, NCI, NIH. Hospital Clinico San Carlos (HCSC): HCSC was supported by RETICC 06/0020/0021, FIS research grant 09/00859, Instituto de Salud Carlos III, Spanish Ministry of Economy and Competitivity, and the European Regional Development Fund (ERDF). Helsinki Breast Cancer Study (HEBCS): The HEBCS was financially supported by the Helsinki University Central Hospital Research Fund, Academy of Finland (132473), the Finnish Cancer Society, the Nordic Cancer Union, and the Sigrid Juselius Foundation. Study of Genetic Mutations in Breast and Ovarian Cancer patients in Hong Kong and Asia (HRBCP): HRBCP is supported by The Hong Kong Hereditary Breast Cancer Family Registry and the Dr. Ellen Li Charitable Foundation, Hong Kong. Molecular Genetic Studies of Breast and Ovarian Cancer in Hungary (HUNBOCS): HUNBOCS was supported by Hungarian Research Grant KTIA-OTKA CK-80745 and the Norwegian EEA Financial Mechanism HU0115/NA/2008-3/O¨ P-9. Institut Catala` d’Oncologia (ICO): The ICO study was supported by the Asociacio´n Espan˜ ola Contra el Ca´ncer, Spanish Health Research Foundation, Ramo´n Areces Foundation, Carlos III Health Institute, Catalan Health Institute, and Autonomous Government of Catalonia and contract grant numbers: ISCIIIRETIC RD06/0020/1051, PI09/02483, PI10/ 01422, PI10/00748, 2009SGR290, and 2009SGR283. International Hereditary Cancer Centre (IHCC): Supported by the Polish Foundation of Science. Katarzyna Jaworska is a fellow of International PhD program, Postgraduate School of Molecular Medicine, Warsaw Medical University. Iceland Landspitali–University Hospital (ILUH): The ILUH group was supported by the Icelandic Association ‘‘Walking for Breast Cancer Research’’ and by the Landspitali University Hospital Research Fund. INterdisciplinary HEalth Research Internal Team BReast CAncer susceptibility (INHERIT): INHERIT work was supported by the Canadian Institutes of Health Research for the ‘‘CIHR Team in Familial Risks of Breast Cancer’’ program, the Canadian Breast Cancer Research Alliance grant 019511 and the Ministry of Economic Development, Innovation and Export Trade grant PSR-SIIRI-701. Jacques Simard is Chairholder of the Canada Research Chair in Oncogenetics. Istituto Oncologico Veneto (IOVHBOCS): The IOVHBOCS study was supported by Ministero dell’Istruzione, dell’Universita` e della Ricerca and Ministero della Salute (‘‘Progetto Tumori Femminili’’ and RFPS 2006-5-341353,ACC2/R6.9’’). Kathleen Cuningham Consortium for Research into Familial Breast Cancer (kConFab): kConFab is supported by grants from the National Breast Cancer Foundation and the National Health and Medical Research Council (NHMRC) and by the Queensland Cancer Fund; the Cancer Councils of New South Wales, Victoria, Tasmania, and South Australia; and the Cancer Foundation of Western Australia. Amanda B. Spurdle is an NHMRC Senior Research Fellow. The Clinical Follow Up Study was funded from 2001–2009 by NHMRC and currently by the National Breast Cancer Foundation and Cancer Australia #628333. Mayo Clinic (MAYO): MAYO is supported by NIH grant CA128978, an NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), a U.S. Department of Defence Ovarian Cancer Idea award (W81XWH-10-1-0341) and grants from the Breast Cancer Research Foundation and the Komen Foundation for the Cure. McGill University (MCGILL): The McGill Study was supported by Jewish General Hospital Weekend to End Breast Cancer, Quebec Ministry of Economic Development, Innovation, and Export Trade. Memorial Sloan-Kettering Cancer Center (MSKCC): The MSKCC study was supported by Breast Cancer Research Foundation, Niehaus Clinical Cancer Genetics Initiative, Andrew Sabin Family Foundation, and Lymphoma Foundation. Modifier Study of Quantitative Effects on Disease (MODSQUAD): MODSQUAD was supported by the European Regional Development Fund and the State Budget of the Czech Republic (RECAMO, CZ.1.05/2.1.00/03.0101). Women’s College Research Institute, Toronto (NAROD): NAROD was supported by NIH grant: 1R01 CA149429-01. National Cancer Institute (NCI): Drs. Mark H. Greene and Phuong L. Mai were supported by the Intramural Research Program of the US National Cancer Institute, NIH, and by support services contracts NO2-CP-11019-50 and N02-CP-65504 with Westat, Rockville, MD. National Israeli Cancer Control Center (NICCC): NICCC is supported by Clalit Health Services in Israel. Some of its activities are supported by the Israel Cancer Association and the Breast Cancer Research Foundation (BCRF), NY. N. N. Petrov Institute of Oncology (NNPIO): The NNPIO study has been supported by the Russian Foundation for Basic Research (grants 11-04-00227, 12-04-00928, and 12-04-01490), the Federal Agency for Science and Innovations, Russia (contract 02.740.11.0780), and through a Royal Society International Joint grant (JP090615). The Ohio State University Comprehensive Cancer Center (OSU-CCG): OSUCCG is supported by the Ohio State University Comprehensive Cancer Center. South East Asian Breast Cancer Association Study (SEABASS): SEABASS is supported by the Ministry of Science, Technology and Innovation, Ministry of Higher Education (UM.C/HlR/MOHE/06) and Cancer Research Initiatives Foundation. Sheba Medical Centre (SMC): The SMC study was partially funded through a grant by the Israel Cancer Association and the funding for the Israeli Inherited Breast Cancer Consortium. Swedish Breast Cancer Study (SWE-BRCA): SWE-BRCA collaborators are supported by the Swedish Cancer Society. The University of Chicago Center for Clinical Cancer Genetics and Global Health (UCHICAGO): UCHICAGO is supported by grants from the US National Cancer Institute (NIH/NCI) and by the Ralph and Marion Falk Medical Research Trust, the Entertainment Industry Fund National Women’s Cancer Research Alliance, and the Breast Cancer Research Foundation. University of California Los Angeles (UCLA): The UCLA study was supported by the Jonsson Comprehensive Cancer Center Foundation and the Breast Cancer Research Foundation. University of California San Francisco (UCSF): The UCSF study was supported by the UCSF Cancer Risk Program and the Helen Diller Family Comprehensive Cancer Center. United Kingdom Familial Ovarian Cancer Registries (UKFOCR): UKFOCR was supported by a project grant from CRUK to Paul Pharoah. University of Pennsylvania (UPENN): The UPENN study was supported by the National Institutes of Health (NIH) (R01-CA102776 and R01-CA083855), Breast Cancer Research Foundation, Rooney Family Foundation, Susan G. Komen Foundation for the Cure, and the Macdonald Family Foundation. Victorian Familial Cancer Trials Group (VFCTG): The VFCTG study was supported by the Victorian Cancer Agency, Cancer Australia, and National Breast Cancer Foundation. Women’s Cancer Research Initiative (WCRI): The WCRI at the Samuel Oschin Comprehensive Cancer Institute, Cedars Sinai Medical Center, Los Angeles, is funded by the American Cancer Society Early Detection Professorship (SIOP-06- 258-01-COUN). en_US
dc.description.uri http://www.plosgenetics.org en_US
dc.identifier.citation Couch FJ, Wang X, McGuffog L, Lee A, Olswold C, et al. (2013) Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk. PLoS Genet 9(3): e1003212. DOI: 10.1371/journal.pgen.1003212 en_US
dc.identifier.issn 1553-7390
dc.identifier.other 10.1371/journal.pgen.1003212
dc.identifier.uri http://hdl.handle.net/2263/21666
dc.language.iso en en_US
dc.publisher Public Library of Science en_US
dc.rights © 2013 Couch et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License en_US
dc.subject Cancer en_US
dc.subject Breast cancer en_US
dc.subject Ovarian cancer en_US
dc.title Genome-wide association study in BRCA1 mutation carriers identifies Novel Loci associated with breast and ovarian cancer risk en_US
dc.type Article en_US


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