Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

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.L., Peock S., Stoppa-Lyonnet D., Jakubowska A., Radice P., Schmutzler R.K., Domchek S.M., Piedmonte M., Singer C.F., Friedman E., Thomassen M., Hansen T.V.O., 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., Ewart Toland A., 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., Balmana 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.M., Seynaeve C., Gomez Garcia E.B., van Leeuwen F.E., Meijers-Heijboer H.E.J., Gille J.J.P., Ausems M.G.E.M., Blok M.J., Ligtenberg M.J.L., Rookus M.A., Devilee P., Verhoef S., van Os T.A.M., Wijnen J.T., 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., Leone M., Pujol P., Mazoyer S., Bignon Y.-J., Zlowocka-Perlowska 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.F., 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., Jonson L., Andersen M.K., Ding Y.C., Steele L., Foretova L., Teule 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., Aittomaki K., Muranen T.A., Duran M., Chung W.K., Lasa A., Dorfling C.M., Miron A., 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., Thorne H., Niedermayr E., Borg A., Olsson H., Jernstrom H., Henriksson K., Harbst K., Soller M., Loman N., Kristoffersson U., Ofverholm A., Nordling M., Karlsson P., Einbeigi Z., von Wachenfeldt A., Liljegren A., Lindblom A., Arver B., Bustinza G.B., Rantala J., Melin B., Ardnor C.E., Emanuelsson M., Ehrencrona H., Pigg M.H., Rosenquist R., Stenmark-Askmalm M., Liedgren S., Rookus M.A., Hogervorst F.B.L., Verhoef S., van Leeuwen F.E., Schmidt M.K., de Lange J., Collee J.M., van den Ouweland A.M.W., Hooning M.J., Seynaeve C., van Asperen C.J., Wijnen J.T., Tollenaar R.A., Devilee P., van Cronenburg T.C.T.E.F., Kets C.M., Mensenkamp A.R., Ausems M.G.E.M., van der Luijt R.B., Aalfs C.M., van Os T.A.M., Gille J.J.P., Waisfisz Q., Meijers-Heijboer H.E.J., Gomez-Garcia E.B., Blok M.J., Oosterwijk J.C., van der Hout H., Mourits M.J., de Bock G.H., Peock S., Frost D., Ellis S., Fineberg E., Platte R., Miedzybrodzka Z., Gregory H., Morrison P., Jeffers L., Cole T., Ong K.-R., Hoffman J., Donaldson A., James M., Tischkowitz M., Paterson J., Taylor A., Murray A., Rogers M.T., McCann E., Kennedy M.J., Barton D., Porteous M., Drummond S., Brewer C., Kivuva E., Searle A., Goodman S., Hill K., Davidson R., Murday V., Bradshaw N., Snadden L., Longmuir M., Watt C., Gibson S., Haque E., Tobias E., Duncan A., Izatt L., Jacobs C., Langman C., Dorkins H., Brady A., Melville A., Randhawa K., Barwell J., Adlard J., Serra-Feliu G., Ellis I., Houghton C., Evans D.G., Lalloo F., Taylor J., Side L., Male A., Berlin C., Eason J., Collier R., Douglas F., Claber O., Jobson I., Walker L., McLeod D., Halliday D., Durell S., Stayner B., Eeles R.A., Shanley S., Rahman N., Houlston R., Stormorken A., Bancroft E., Page E., Ardern-Jones A., Kohut K., Wiggins J., Castro E., Killick E., Martin S., Rea G., Kulkarni A., Cook J., Quarrell O., Bardsley C., Hodgson S., Goff S., Brice G., Winchester L., Eddy C., Tripathi V., Attard V., Lehmann A., Eccles D., Lucassen A., Crawford G., McBride D., Smalley S., Sinilnikova O., Mazoyer S., Damiola F., Barjhoux L., Verny-Pierre C., Giraud S., Leone M., Stoppa-Lyonnet D., Gauthier-Villars M., Buecher B., Houdayer C., Moncoutier V., Belotti M., Tirapo C., de Pauw A., Bressac-de-Paillerets B., Caron O., Bignon Y.-J., Uhrhammer N., Lasset C., Bonadona V., Handallou S., Hardouin A., Berthet P., Sobol H., Bourdon V., Noguchi T., Remenieras A., Eisinger F., Coupier I., Pujol P., Peyrat J.-P., Fournier J., Revillion F., Vennin P., Adenis C., Rouleau E., Lidereau R., Demange L., Nogues C., Muller D., Fricker J.-P., Barouk-Simonet E., Bonnet F., Bubien V., Sevenet N., Longy M., Toulas C., Guimbaud R., Gladieff L., Feillel V., Leroux D., Dreyfus H., Rebischung C., Peysselon M., Coron F., Faivre L., Prieur F., Lebrun M., Kientz C., Ferrer S.F., Frenay M., Venat-Bouvet L., Delnatte C., Mortemousque I., Coulet F., Colas C., Soubrier F., Sokolowska J., Bronner M., Lynch H.T., Snyder C.L., Angelakos M., Maskiell J. and Dite G. (2013) Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk. PLoS Genetics, 9 3: e1003212-1-e1003212-21. doi:10.1371/journal.pgen.1003212

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Author 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.L.
Peock S.
Stoppa-Lyonnet D.
Jakubowska A.
Radice P.
Schmutzler R.K.
Domchek S.M.
Piedmonte M.
Singer C.F.
Friedman E.
Thomassen M.
Hansen T.V.O.
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.
Ewart Toland A.
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.
Balmana 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.M.
Seynaeve C.
Gomez Garcia E.B.
van Leeuwen F.E.
Meijers-Heijboer H.E.J.
Gille J.J.P.
Ausems M.G.E.M.
Blok M.J.
Ligtenberg M.J.L.
Rookus M.A.
Devilee P.
Verhoef S.
van Os T.A.M.
Wijnen J.T.
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.
Leone M.
Pujol P.
Mazoyer S.
Bignon Y.-J.
Zlowocka-Perlowska 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.F.
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.
Jonson L.
Andersen M.K.
Ding Y.C.
Steele L.
Foretova L.
Teule 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.
Aittomaki K.
Muranen T.A.
Duran M.
Chung W.K.
Lasa A.
Dorfling C.M.
Miron A.
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.
Thorne H.
Niedermayr E.
Borg A.
Olsson H.
Jernstrom H.
Henriksson K.
Harbst K.
Soller M.
Loman N.
Kristoffersson U.
Ofverholm A.
Nordling M.
Karlsson P.
Einbeigi Z.
von Wachenfeldt A.
Liljegren A.
Lindblom A.
Arver B.
Bustinza G.B.
Rantala J.
Melin B.
Ardnor C.E.
Emanuelsson M.
Ehrencrona H.
Pigg M.H.
Rosenquist R.
Stenmark-Askmalm M.
Liedgren S.
Rookus M.A.
Hogervorst F.B.L.
Verhoef S.
van Leeuwen F.E.
Schmidt M.K.
de Lange J.
Collee J.M.
van den Ouweland A.M.W.
Hooning M.J.
Seynaeve C.
van Asperen C.J.
Wijnen J.T.
Tollenaar R.A.
Devilee P.
van Cronenburg T.C.T.E.F.
Kets C.M.
Mensenkamp A.R.
Ausems M.G.E.M.
van der Luijt R.B.
Aalfs C.M.
van Os T.A.M.
Gille J.J.P.
Waisfisz Q.
Meijers-Heijboer H.E.J.
Gomez-Garcia E.B.
Blok M.J.
Oosterwijk J.C.
van der Hout H.
Mourits M.J.
de Bock G.H.
Peock S.
Frost D.
Ellis S.
Fineberg E.
Platte R.
Miedzybrodzka Z.
Gregory H.
Morrison P.
Jeffers L.
Cole T.
Ong K.-R.
Hoffman J.
Donaldson A.
James M.
Tischkowitz M.
Paterson J.
Taylor A.
Murray A.
Rogers M.T.
McCann E.
Kennedy M.J.
Barton D.
Porteous M.
Drummond S.
Brewer C.
Kivuva E.
Searle A.
Goodman S.
Hill K.
Davidson R.
Murday V.
Bradshaw N.
Snadden L.
Longmuir M.
Watt C.
Gibson S.
Haque E.
Tobias E.
Duncan A.
Izatt L.
Jacobs C.
Langman C.
Dorkins H.
Brady A.
Melville A.
Randhawa K.
Barwell J.
Adlard J.
Serra-Feliu G.
Ellis I.
Houghton C.
Evans D.G.
Lalloo F.
Taylor J.
Side L.
Male A.
Berlin C.
Eason J.
Collier R.
Douglas F.
Claber O.
Jobson I.
Walker L.
McLeod D.
Halliday D.
Durell S.
Stayner B.
Eeles R.A.
Shanley S.
Rahman N.
Houlston R.
Stormorken A.
Bancroft E.
Page E.
Ardern-Jones A.
Kohut K.
Wiggins J.
Castro E.
Killick E.
Martin S.
Rea G.
Kulkarni A.
Cook J.
Quarrell O.
Bardsley C.
Hodgson S.
Goff S.
Brice G.
Winchester L.
Eddy C.
Tripathi V.
Attard V.
Lehmann A.
Eccles D.
Lucassen A.
Crawford G.
McBride D.
Smalley S.
Sinilnikova O.
Mazoyer S.
Damiola F.
Barjhoux L.
Verny-Pierre C.
Giraud S.
Leone M.
Stoppa-Lyonnet D.
Gauthier-Villars M.
Buecher B.
Houdayer C.
Moncoutier V.
Belotti M.
Tirapo C.
de Pauw A.
Bressac-de-Paillerets B.
Caron O.
Bignon Y.-J.
Uhrhammer N.
Lasset C.
Bonadona V.
Handallou S.
Hardouin A.
Berthet P.
Sobol H.
Bourdon V.
Noguchi T.
Remenieras A.
Eisinger F.
Coupier I.
Pujol P.
Peyrat J.-P.
Fournier J.
Revillion F.
Vennin P.
Adenis C.
Rouleau E.
Lidereau R.
Demange L.
Nogues C.
Muller D.
Fricker J.-P.
Barouk-Simonet E.
Bonnet F.
Bubien V.
Sevenet N.
Longy M.
Toulas C.
Guimbaud R.
Gladieff L.
Feillel V.
Leroux D.
Dreyfus H.
Rebischung C.
Peysselon M.
Coron F.
Faivre L.
Prieur F.
Lebrun M.
Kientz C.
Ferrer S.F.
Frenay M.
Venat-Bouvet L.
Delnatte C.
Mortemousque I.
Coulet F.
Colas C.
Soubrier F.
Sokolowska J.
Bronner M.
Lynch H.T.
Snyder C.L.
Angelakos M.
Maskiell J.
Dite G.
Title Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk
Journal name PLoS Genetics   Check publisher's open access policy
ISSN 1553-7390
1553-7404
Publication date 2013
Sub-type Article (original research)
DOI 10.1371/journal.pgen.1003212
Open Access Status DOI
Volume 9
Issue 3
Start page e1003212-1
End page e1003212-21
Total pages 21
Place of publication San Francisco, CA, U.S.A.
Publisher Public Library of Science
Collection year 2014
Language eng
Subject 1311 Genetics
1312 Molecular Biology
1105 Dentistry
1306 Cancer Research
2716 Genetics (clinical)
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.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Medicine Publications
 
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Created: Sun, 23 Feb 2014, 10:02:49 EST by Matthew Lamb on behalf of School of Medicine