Vigorito, Elena, Kuchenbaecker, Karoline B., Beesley, Jonathan ORCID: 0000-0003-1942-325X, Adlard, Julian ORCID: 0000-0002-1693-0435, Agnarsson, Bjarni A., Andrulis, Irene L., Arun, Banu K., Barjhoux, Laure, Belotti, Muriel, Benitez, Javier, Berger, Andreas, Bojesen, Anders ORCID: 0000-0003-4289-8595, Bonanni, Bernardo, Brewer, Carole, Caldes, Trinidad, Caligo, Maria A., Campbell, Ian ORCID: 0000-0002-7773-4155, Chan, Salina B., Claes, Kathleen B. M., Cohn, David E., Cook, Jackie, Daly, Mary B., Damiola, Francesca ORCID: 0000-0002-0238-1252, Davidson, Rosemarie, de Pauw, Antoine, Delnatte, Capucine, Diez, Orland, Domchek, Susan M., Dumont, Martine, Durda, Katarzyna, Dworniczak, Bernd, Easton, Douglas F., Eccles, Diana ORCID: 0000-0002-9935-3169, Ardnor, Christina Edwinsdotter, Eeles, Ros, Ejlertsen, Bent, Ellis, Steve, Evans, D. Gareth, Feliubadalo, Lidia ORCID: 0000-0002-1736-0112, Fostira, Florentia, Foulkes, William D., Friedman, Eitan, Frost, Debra, Gaddam, Pragna, Ganz, Patricia A., Garber, Judy, Garcia-Barberan, Vanesa, Gauthier-Villars, Marion, Gehrig, Andrea, Gerdes, Anne-Marie ORCID: 0000-0002-0328-3320, Giraud, Sophie, Godwin, Andrew K., Goldgar, David E., Hake, Christopher R., Hansen, Thomas V. O., Healey, Sue, Hodgson, Shirley, Hogervorst, Frans B. L., Houdayer, Claude, Hulick, Peter J., Imyanitov, Evgeny N., Isaacs, Claudine, Izatt, Louise, Izquierdo, Angel, Jacobs, Lauren, Jakubowska, Anna ORCID: 0000-0002-5650-0501, Janavicius, Ramunas, Jaworska-Bieniek, Katarzyna, Jensen, Uffe Birk ORCID: 0000-0002-6205-6355, John, Esther M., Vijai, Joseph, Karlan, Beth Y., Kast, Karin, Khan, Sofia ORCID: 0000-0003-4185-8882, Kwong, Ava ORCID: 0000-0002-6968-9489, Laitman, Yael, Lester, Jenny, Lesueur, Fabienne ORCID: 0000-0001-7404-4549, Liljegren, Annelie, Lubinski, Jan ORCID: 0000-0003-2931-3003, Mai, Phuong L., Manoukian, Siranoush, Mazoyer, Sylvie ORCID: 0000-0002-2135-0160, Meindl, Alfons, Mensenkamp, Arjen R., Montagna, Marco, Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Niederacher, Dieter, Olah, Edith, Olopade, Olufunmilayo I., Ong, Kai-ren, Osorio, Ana ORCID: 0000-0001-8124-3984, Park, Sue Kyung, Paulsson-Karlsson, Ylva, Pedersen, Inge Sokilde ORCID: 0000-0002-9902-8040, Peissel, Bernard ORCID: 0000-0001-9233-3571, Peterlongo, Paolo ORCID: 0000-0001-6951-6855, Pfeiler, Georg, Phelan, Catherine M., Piedmonte, Marion, Poppe, Bruce, Angel Pujana, Miquel, Radice, Paolo ORCID: 0000-0001-6298-4111, Rennert, Gad, Rodriguez, Gustavo C., Rookus, Matti A., Ross, Eric A., Schmutzler, Rita Katharina, Simard, Jacques, Singer, Christian F., Slavin, Thomas P., Soucy, Penny, Southey, Melissa ORCID: 0000-0002-6313-9005, Steinemann, Doris, Stoppa-Lyonnet, Dominique, Sukiennicki, Grzegorz, Sutter, Christian, Szabo, Csilla I., Tea, Muy-Kheng, Teixeira, Manuel R., Teo, Soo-Hwang, Terry, Mary Beth, Thomassen, Mads, Tibiletti, Maria Grazia, Tihomirova, Laima, Tognazzo, Silvia ORCID: 0000-0002-6260-1261, van Rensburg, Elizabeth J., Varesco, Liliana ORCID: 0000-0003-4871-6668, Varon-Mateeva, Raymonda, Vratimos, Athanassios, Weitzel, Jeffrey N., McGuffog, Lesley, Kirk, Judy, Toland, Amanda Ewart, Hamann, Ute, Lindor, Noralane, Ramus, Susan J., Greene, Mark H., Couch, Fergus J., Offit, Kenneth, Pharoah, Paul D. P., Chenevix-Trench, Georgia ORCID: 0000-0002-1878-2587 and Antoniou, Antonis C. (2016). Fine-Scale Mapping at 9p22.2 Identifies Candidate Causal Variants That Modify Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers. PLoS One, 11 (7). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1932-6203

Full text not available from this repository.

Abstract

Population-based genome wide association studies have identified a locus at 9p22.2 associated with ovarian cancer risk, which also modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. We conducted fine-scale mapping at 9p22.2 to identify potential causal variants in BRCA1 and BRCA2 mutation carriers. Genotype data were available for 15,252 (2,462 ovarian cancer cases) BRCA1 and 8,211 (631 ovarian cancer cases) BRCA2 mutation carriers. Following genotype imputation, ovarian cancer associations were assessed for 4,873 and 5,020 SNPs in BRCA1 and BRCA2 mutation carriers respectively, within a retrospective cohort analytical framework. In BRCA1 mutation carriers one set of eight correlated candidate causal variants for ovarian cancer risk modification was identified (top SNP rs10124837, HR: 0.73, 95% CI: 0.68 to 0.79, p-value 2x 10-16). These variants were located up to 20 kb upstream of BNC2. In BRCA2 mutation carriers one region, up to 45 kb upstream of BNC2, and containing 100 correlated SNPs was identified as candidate causal (top SNP rs62543585, HR: 0.69, 95% CI: 0.59 to 0.80, p-value 1.0 x 10-6). The candidate causal in BRCA1 mutation carriers did not include the strongest associated variant at this locus in the general population. In sum, we identified a set of candidate causal variants in a region that encompasses the BNC2 transcription start site. The ovarian cancer association at 9p22.2 may be mediated by different variants in BRCA1 mutation carriers and in the general population. Thus, potentially different mechanisms may underlie ovarian cancer risk for mutation carriers and the general population.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Vigorito, ElenaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kuchenbaecker, Karoline B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Beesley, JonathanUNSPECIFIEDorcid.org/0000-0003-1942-325XUNSPECIFIED
Adlard, JulianUNSPECIFIEDorcid.org/0000-0002-1693-0435UNSPECIFIED
Agnarsson, Bjarni A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Andrulis, Irene L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Arun, Banu K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Barjhoux, LaureUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Belotti, MurielUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Benitez, JavierUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Berger, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bojesen, AndersUNSPECIFIEDorcid.org/0000-0003-4289-8595UNSPECIFIED
Bonanni, BernardoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brewer, CaroleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Caldes, TrinidadUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Caligo, Maria A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Campbell, IanUNSPECIFIEDorcid.org/0000-0002-7773-4155UNSPECIFIED
Chan, Salina B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Claes, Kathleen B. M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cohn, David E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cook, JackieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Daly, Mary B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Damiola, FrancescaUNSPECIFIEDorcid.org/0000-0002-0238-1252UNSPECIFIED
Davidson, RosemarieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
de Pauw, AntoineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Delnatte, CapucineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Diez, OrlandUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Domchek, Susan M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dumont, MartineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Durda, KatarzynaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dworniczak, BerndUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Easton, Douglas F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eccles, DianaUNSPECIFIEDorcid.org/0000-0002-9935-3169UNSPECIFIED
Ardnor, Christina EdwinsdotterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eeles, RosUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ejlertsen, BentUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ellis, SteveUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Evans, D. GarethUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Feliubadalo, LidiaUNSPECIFIEDorcid.org/0000-0002-1736-0112UNSPECIFIED
Fostira, FlorentiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Foulkes, William D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Friedman, EitanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Frost, DebraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gaddam, PragnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ganz, Patricia A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Garber, JudyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Garcia-Barberan, VanesaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gauthier-Villars, MarionUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gehrig, AndreaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gerdes, Anne-MarieUNSPECIFIEDorcid.org/0000-0002-0328-3320UNSPECIFIED
Giraud, SophieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Godwin, Andrew K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Goldgar, David E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hake, Christopher R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hansen, Thomas V. O.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Healey, SueUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hodgson, ShirleyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hogervorst, Frans B. L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Houdayer, ClaudeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hulick, Peter J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Imyanitov, Evgeny N.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Isaacs, ClaudineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Izatt, LouiseUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Izquierdo, AngelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jacobs, LaurenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jakubowska, AnnaUNSPECIFIEDorcid.org/0000-0002-5650-0501UNSPECIFIED
Janavicius, RamunasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jaworska-Bieniek, KatarzynaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jensen, Uffe BirkUNSPECIFIEDorcid.org/0000-0002-6205-6355UNSPECIFIED
John, Esther M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vijai, JosephUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Karlan, Beth Y.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kast, KarinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Khan, SofiaUNSPECIFIEDorcid.org/0000-0003-4185-8882UNSPECIFIED
Kwong, AvaUNSPECIFIEDorcid.org/0000-0002-6968-9489UNSPECIFIED
Laitman, YaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lester, JennyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lesueur, FabienneUNSPECIFIEDorcid.org/0000-0001-7404-4549UNSPECIFIED
Liljegren, AnnelieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lubinski, JanUNSPECIFIEDorcid.org/0000-0003-2931-3003UNSPECIFIED
Mai, Phuong L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Manoukian, SiranoushUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mazoyer, SylvieUNSPECIFIEDorcid.org/0000-0002-2135-0160UNSPECIFIED
Meindl, AlfonsUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mensenkamp, Arjen R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Montagna, MarcoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nathanson, Katherine L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Neuhausen, Susan L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nevanlinna, HeliUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Niederacher, DieterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Olah, EdithUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Olopade, Olufunmilayo I.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ong, Kai-renUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Osorio, AnaUNSPECIFIEDorcid.org/0000-0001-8124-3984UNSPECIFIED
Park, Sue KyungUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Paulsson-Karlsson, YlvaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pedersen, Inge SokildeUNSPECIFIEDorcid.org/0000-0002-9902-8040UNSPECIFIED
Peissel, BernardUNSPECIFIEDorcid.org/0000-0001-9233-3571UNSPECIFIED
Peterlongo, PaoloUNSPECIFIEDorcid.org/0000-0001-6951-6855UNSPECIFIED
Pfeiler, GeorgUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Phelan, Catherine M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Piedmonte, MarionUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Poppe, BruceUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Angel Pujana, MiquelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Radice, PaoloUNSPECIFIEDorcid.org/0000-0001-6298-4111UNSPECIFIED
Rennert, GadUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rodriguez, Gustavo C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rookus, Matti A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ross, Eric A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schmutzler, Rita KatharinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Simard, JacquesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Singer, Christian F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Slavin, Thomas P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Soucy, PennyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Southey, MelissaUNSPECIFIEDorcid.org/0000-0002-6313-9005UNSPECIFIED
Steinemann, DorisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stoppa-Lyonnet, DominiqueUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sukiennicki, GrzegorzUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sutter, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Szabo, Csilla I.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tea, Muy-KhengUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Teixeira, Manuel R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Teo, Soo-HwangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Terry, Mary BethUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thomassen, MadsUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tibiletti, Maria GraziaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tihomirova, LaimaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tognazzo, SilviaUNSPECIFIEDorcid.org/0000-0002-6260-1261UNSPECIFIED
van Rensburg, Elizabeth J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Varesco, LilianaUNSPECIFIEDorcid.org/0000-0003-4871-6668UNSPECIFIED
Varon-Mateeva, RaymondaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vratimos, AthanassiosUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weitzel, Jeffrey N.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
McGuffog, LesleyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kirk, JudyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Toland, Amanda EwartUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hamann, UteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lindor, NoralaneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ramus, Susan J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Greene, Mark H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Couch, Fergus J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Offit, KennethUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pharoah, Paul D. P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chenevix-Trench, GeorgiaUNSPECIFIEDorcid.org/0000-0002-1878-2587UNSPECIFIED
Antoniou, Antonis C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-269522
DOI: 10.1371/journal.pone.0158801
Journal or Publication Title: PLoS One
Volume: 11
Number: 7
Date: 2016
Publisher: PUBLIC LIBRARY SCIENCE
Place of Publication: SAN FRANCISCO
ISSN: 1932-6203
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; BREAST; INVESTIGATORS; CONSORTIUM; PATHOLOGY; CENTLEINMultiple languages
Multidisciplinary SciencesMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/26952

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