Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/126827
Title: Fine-Scale Mapping at 9p22.2 Identifies Candidate Causal Variants That Modify Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers
Author: Vigorito, Elena
Kuchenbaecker, Karoline B.
Beesley, Jonathan
Adlard, Julian
Agnarsson, Bjarni A.
Andrulis, Irene L.
Arun, Banu K.
Barjhoux, Laure
Belotti, Muriel
Benitez, Javier
Berger, Andreas
Goldgar, David E.
Ganz, Patricia A.
Easton, Douglas F.
Eccles, Diana
Edwinsdotter Ardnor, Christina
Gehrig, Andrea
Eeles, Ros
Evans, D. Gareth
Feliubadaló i Elorza, Maria Lídia
Garber, Judy
Mazoyer, Sylvie
Gerdes, Anne-Marie
Hake, Christopher R.
Houdayer, Claude
Nathanson, Katherine L.
Hansen, Thomas V. O.
Hulick, Peter J.
Imyanitov, Evgeny N.
Mensenkamp, Arjen R.
Isaacs, Claudine
Neuhausen, Susan L.
Lester, Jenny
Izatt, Louise
Olopade, Olufunmilayo I.
Izquierdo i Font, Àngel Xavier
Paulsson-Karlsson, Ylva
Manoukian, Siranoush
Jacobs, Lauren
Phelan, Catherine M.
Jakubowska, Anna
Janavicius, Ramunas
Poppe, Bruce
Lesueur, Fabienne
Jaworska-Bieniek, Katarzyna
Jensen, Uffe Birk
Nevanlinna, Heli
John, Esther M.
Vijai, Joseph
Peissel, Bernard
Ong, Kai-ren
Karlan, Beth Y.
Kast, Karin
Pedersen, Inge Sokilde
Liljegren, Annelie
Khan, Sofia
Montagna, Marco
Kwong, Ava
Piedmonte, Marion
Laitman, Yael
Niederacher, Dieter
Osorio, Ana
Lubinski, Jan
Mai, Phuong L.
Meindl, Alfons
Olah, Edith
KConFab Investigators
Tognazzo, Silvia
Park, Sue Kyung
Peterlongo, Paolo
Pujana Genestar, M. Ángel
Vratimos, Athanassios
Pfeiler, Georg
Radice, Paolo
Rennert, Gad
Varesco, Liliana
Rodriguez, Gustavo C.
Weitzel, Jeffrey N.
Teixeira, Manuel R.
Rookus, Matti A.
Hamann, Ute
Ross, Eric A.
Couch, Fergus J.
Tihomirova, Laima
Schmutzler, Rita Katharina
Bojesen, Anders
Simard, Jacques
Singer, Christian F.
Brewer, Carole
Teo, Soo-Hwang
Slavin, Thomas P.
Soucy, Penny
McGuffog, Lesley
Southey, Melissa
Steinemann, Doris
Pharoah, Paul D. P.
Lindor, Noralane
Stoppa-Lyonnet, Dominique
Sukiennicki, Grzegorz
Offit, Kenneth
Terry, Mary Beth
Sutter, Christian
Varon-Mateeva, Raymonda
Szabo, Csilla I.
Bonanni, Bernardo
Tea, Muy-Kheng
Kirk, Judy
Ramus, Susan J.
Thomassen, Mads
Tibiletti, Maria Grazia
van Rensburg, Elizabeth J.
Toland, Amanda Ewart
Greene, Mark H.
Friedman, Eitan
Chenevix-Trench, Georgia
Caldes, Trinidad
Antoniou, Antonis C.
Fostira, Florentia
Caligo, Maria A.
Campbell, Ian
Frost, Debra
Chan, Salina B.
Garcia Barberan, Vanesa
Claes, Kathleen B. M.
Ejlertsen, Bent
Giraud, Sophie
Cohn, David E.
Healey, Sue
Cook, Jackie
Hogervorst, Frans B. L.
Daly, Mary B.
Damiola, Francesca
Davidson, Rosemarie
Gaddam, Pragna
Pauw, Antoine de
Ellis, Steve
Delnatte, Capucine
Gauthier-Villars, Marion
Díez Gibert, Orland
Domchek, Susan M.
Godwin, Andrew K.
Foulkes, William D.
Dumont, Martine
Durda, Katarzyna
Hodgson, Shirley
Dworniczak, Bernd
Keywords: Càncer d'ovari
Oncogens
Ovarian cancer
Oncogenes
Issue Date: 27-Jul-2016
Publisher: Public Library of Science (PLoS)
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.
Note: Reproducció del document publicat a: https://doi.org/10.1371/journal.pone.0158801
It is part of: PLoS One, 2016, vol. 11, num. 7, p. e0158801
URI: http://hdl.handle.net/2445/126827
Related resource: https://doi.org/10.1371/journal.pone.0158801
Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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