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Candidate Genetic Modifiers for Breast and Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers
- Peterlongo, Paolo;
- Chang-Claude, Jenny;
- Moysich, Kirsten B;
- Rudolph, Anja;
- Schmutzler, Rita K;
- Simard, Jacques;
- Soucy, Penny;
- Eeles, Rosalind A;
- Easton, Douglas F;
- Hamann, Ute;
- Wilkening, Stefan;
- Chen, Bowang;
- Rookus, Matti A;
- Schmidt, Marjanka K;
- van der Baan, Frederieke H;
- Spurdle, Amanda B;
- Walker, Logan C;
- Lose, Felicity;
- Maia, Ana-Teresa;
- Montagna, Marco;
- Matricardi, Laura;
- Lubinski, Jan;
- Jakubowska, Anna;
- Garcia, Encarna B Gómez;
- Olopade, Olufunmilayo I;
- Nussbaum, Robert L;
- Nathanson, Katherine L;
- Domchek, Susan M;
- Rebbeck, Timothy R;
- Arun, Banu K;
- Karlan, Beth Y;
- Orsulic, Sandra;
- Lester, Jenny;
- Chung, Wendy K;
- Miron, Alex;
- Southey, Melissa C;
- Goldgar, David E;
- Buys, Saundra S;
- Janavicius, Ramunas;
- Dorfling, Cecilia M;
- van Rensburg, Elizabeth J;
- Ding, Yuan Chun;
- Neuhausen, Susan L;
- Hansen, Thomas VO;
- Gerdes, Anne-Marie;
- Ejlertsen, Bent;
- Jønson, Lars;
- Osorio, Ana;
- Martínez-Bouzas, Cristina;
- Benitez, Javier;
- Conway, Edye E;
- Blazer, Kathleen R;
- Weitzel, Jeffrey N;
- Manoukian, Siranoush;
- Peissel, Bernard;
- Zaffaroni, Daniela;
- Scuvera, Giulietta;
- Barile, Monica;
- Ficarazzi, Filomena;
- Mariette, Frederique;
- Fortuzzi, Stefano;
- Viel, Alessandra;
- Giannini, Giuseppe;
- Papi, Laura;
- Martayan, Aline;
- Tibiletti, Maria Grazia;
- Radice, Paolo;
- Vratimos, Athanassios;
- Fostira, Florentia;
- Garber, Judy E;
- Donaldson, Alan;
- Brewer, Carole;
- Foo, Claire;
- Evans, D Gareth R;
- Frost, Debra;
- Eccles, Diana;
- Brady, Angela;
- Cook, Jackie;
- Tischkowitz, Marc;
- Adlard, Julian;
- Barwell, Julian;
- Walker, Lisa;
- Izatt, Louise;
- Side, Lucy E;
- Kennedy, M John;
- Rogers, Mark T;
- Porteous, Mary E;
- Morrison, Patrick J;
- Platte, Radka;
- Davidson, Rosemarie;
- Hodgson, Shirley V;
- Ellis, Steve;
- Cole, Trevor;
- behalf of EMBRACE, on;
- Godwin, Andrew K;
- Claes, Kathleen;
- Van Maerken, Tom;
- Meindl, Alfons;
- Gehrig, Andrea;
- Sutter, Christian;
- Engel, Christoph;
- Niederacher, Dieter;
- Steinemann, Doris;
- Plendl, Hansjoerg;
- Kast, Karin;
- Rhiem, Kerstin;
- Ditsch, Nina;
- Arnold, Norbert;
- Varon-Mateeva, Raymonda;
- Wappenschmidt, Barbara;
- Wang-Gohrke, Shan;
- Paillerets, Brigitte Bressac-de;
- Buecher, Bruno;
- Delnatte, Capucine;
- Houdayer, Claude;
- Stoppa-Lyonnet, Dominique;
- Damiola, Francesca;
- Coupier, Isabelle;
- Barjhoux, Laure;
- Venat-Bouvet, Laurence;
- Golmard, Lisa;
- Boutry-Kryza, Nadia;
- Sinilnikova, Olga M;
- Caron, Olivier;
- Pujol, Pascal;
- Mazoyer, Sylvie;
- Belotti, Muriel;
- Collaborators, on behalf of GEMO Study;
- Piedmonte, Marion;
- Friedlander, Michael L;
- Rodriguez, Gustavo C;
- Copeland, Larry J;
- de la Hoya, Miguel;
- Segura, Pedro Perez;
- Nevanlinna, Heli;
- Aittomäki, Kristiina;
- van Os, Theo AM;
- Meijers-Heijboer, Hanne EJ;
- van der Hout, Annemarie H;
- Vreeswijk, Maaike PG;
- Hoogerbrugge, Nicoline;
- Ausems, Margreet GEM;
- van Doorn, Helena C;
- Collée, J Margriet;
- behalf of HEBON, on;
- Olah, Edith;
- Diez, Orland;
- Blanco, Ignacio;
- Lazaro, Conxi;
- Brunet, Joan;
- Feliubadalo, Lidia;
- Cybulski, Cezary;
- Gronwald, Jacek;
- Durda, Katarzyna;
- Jaworska-Bieniek, Katarzyna;
- Sukiennicki, Grzegorz;
- Arason, Adalgeir;
- Chiquette, Jocelyne;
- Teixeira, Manuel R;
- Olswold, Curtis;
- Couch, Fergus J;
- Lindor, Noralane M;
- Wang, Xianshu;
- Szabo, Csilla I;
- Offit, Kenneth;
- Corines, Marina;
- Jacobs, Lauren;
- Robson, Mark E;
- Zhang, Liying;
- Joseph, Vijai;
- Berger, Andreas;
- Singer, Christian F;
- Rappaport, Christine;
- Kaulich, Daphne Geschwantler;
- Pfeiler, Georg;
- Tea, Muy-Kheng M;
- Phelan, Catherine M;
- Greene, Mark H;
- Mai, Phuong L;
- Rennert, Gad;
- Mulligan, Anna Marie;
- Glendon, Gord;
- Tchatchou, Sandrine;
- Andrulis, Irene L;
- Toland, Amanda Ewart;
- Bojesen, Anders;
- Pedersen, Inge Sokilde;
- Thomassen, Mads;
- Jensen, Uffe Birk;
- Laitman, Yael;
- Rantala, Johanna;
- von Wachenfeldt, Anna;
- Ehrencrona, Hans;
- Askmalm, Marie Stenmark;
- Borg, Åke;
- Kuchenbaecker, Karoline B;
- McGuffog, Lesley;
- Barrowdale, Daniel;
- Healey, Sue;
- Lee, Andrew;
- Pharoah, Paul DP;
- Chenevix-Trench, Georgia;
- Investigators, on behalf of KConFab;
- Antoniou, Antonis C;
- Friedman, Eitan
- et al.
Published Web Location
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4294951/pdf/nihms644448.pdfNo data is associated with this publication.
Abstract
Background
BRCA1 and BRCA2 mutation carriers are at substantially increased risk for developing breast and ovarian cancer. The incomplete penetrance coupled with the variable age at diagnosis in carriers of the same mutation suggests the existence of genetic and nongenetic modifying factors. In this study, we evaluated the putative role of variants in many candidate modifier genes.Methods
Genotyping data from 15,252 BRCA1 and 8,211 BRCA2 mutation carriers, for known variants (n = 3,248) located within or around 445 candidate genes, were available through the iCOGS custom-designed array. Breast and ovarian cancer association analysis was performed within a retrospective cohort approach.Results
The observed P values of association ranged between 0.005 and 1.000. None of the variants was significantly associated with breast or ovarian cancer risk in either BRCA1 or BRCA2 mutation carriers, after multiple testing adjustments.Conclusion
There is little evidence that any of the evaluated candidate variants act as modifiers of breast and/or ovarian cancer risk in BRCA1 or BRCA2 mutation carriers.Impact
Genome-wide association studies have been more successful at identifying genetic modifiers of BRCA1/2 penetrance than candidate gene studies.Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.