Please use this identifier to cite or link to this item: https://hdl.handle.net/20.500.12530/25743
Title: Fine-Scale Mapping at 9p22.2 Identifies Candidate Causal Variants That Modify Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers.
Authors: 
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
Bojesen, Anders
Bonanni, Bernardo
Brewer, Carole
Caldes, Trinidad
Caligo, Maria A
Campbell, Ian
Chan, Salina B
Claes, Kathleen B M
Cohn, David E
Cook, Jackie
Daly, Mary B
Damiola, Francesca
Davidson, Rosemarie
Pauw, Antoine de
Delnatte, Capucine
Diez, Orland
Domchek, Susan M
Dumont, Martine
Durda, Katarzyna
Dworniczak, Bernd
Easton, Douglas F
Eccles, Diana
Edwinsdotter Ardnor, Christina
Eeles, Ros
Ejlertsen, Bent
Ellis, Steve
Evans, D Gareth
Feliubadalo, Lidia
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
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
Janavicius, Ramunas
Jaworska-Bieniek, Katarzyna
Jensen, Uffe Birk
John, Esther M
Vijai, Joseph
Karlan, Beth Y
Kast, Karin
Investigators, KConFab
Khan, Sofia
Kwong, Ava
Laitman, Yael
Lester, Jenny
Lesueur, Fabienne
Liljegren, Annelie
Lubinski, Jan
Mai, Phuong L
Manoukian, Siranoush
Mazoyer, Sylvie
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
Park, Sue Kyung
Paulsson-Karlsson, Ylva
Pedersen, Inge Sokilde
Peissel, Bernard
Peterlongo, Paolo
Pfeiler, Georg
Phelan, Catherine M
Piedmonte, Marion
Poppe, Bruce
Pujana, Miquel Angel
Radice, Paolo
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
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
van Rensburg, Elizabeth J
Varesco, Liliana
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
Antoniou, Antonis C
Mesh: 
Issue Date: 2016
Citation: PLoS ONE.2016;(11)7:e0158801
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 BRCA 2 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 2× 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 × 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.
PMID: 27463617
URI: https://hdl.handle.net/20.500.12530/25743
Rights: openAccess
Appears in Collections:Fundaciones e Institutos de Investigación > IIS H. U. Clínico San Carlos > Artículos

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