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Full-text held externally
- PMID: 25336561
- UKPMCID: 25336561
- DOI: 10.1158/1055-9965.EPI-14-0532
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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; Gomez-Garcia, Encarna B; 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, Cecelia M; van Rensburg, Elizabeth J; Ding, Yuan Chun; Neuhausen, Susan L; Hansen, Thomas V O; Gerdes, Anne-Marie; Ejlertsen, Bent; Jønson, Lars; Osorio, Ana; Martinez-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; 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; Bressac-de Paillerets, Brigitte; 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; Piedmonte, Marion; Friedlander, Michael L; Rodriguez, Gustavo C; Copeland, Larry J; de la Hoya, Miguel; Perez Segura, Pedro; Nevanlinna, Heli; Aittomäki, Kristiina; van Os, Theo A M; Meijers-Heijboer, Hanne E J; Van der Hout, Annemarie H; Vreeswijk, Maaike P G; Hoogerbrugge, Nicoline; Ausems, Margreet G E M; Van Doorn, Helena C; CollĂ©e, J Margriet; Olah, Edith; DĂez, Orland; Blanco, Ignacio; Lazaro, Conxi; Brunet, Joan; FeliubadalĂł, LĂdia; 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; Zhang, Liying; Joseph, Vijai; Berger, Andreas; Singer, Christian F; Rappaport, Christine; Geschwantler Kaulich, Daphne; 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; Stenmark Askmalm, Marie; Borg, Ake; Kuchenbaecker, Karoline B; McGuffog, Lesley; Barrowdale, Daniel; Healey, Sue; Lee, Andrew; Pharoah, Paul D P; Chenevix-Trench, Georgia; Antoniou, Antonis C; Friedman, Eitan
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2014;.
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Full-text held externally
- PMID: 25336561
- UKPMCID: 25336561
- DOI: 10.1158/1055-9965.EPI-14-0532
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 non-genetic 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 0.005-1.000. 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.
Bibliographic metadata
- 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
- Gomez-Garcia, Encarna B
- 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, Cecelia M
- van Rensburg, Elizabeth J
- Ding, Yuan Chun
- Neuhausen, Susan L
- Hansen, Thomas V O
- Gerdes, Anne-Marie
- Ejlertsen, Bent
- Jønson, Lars
- Osorio, Ana
- Martinez-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
- 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
- Bressac-de Paillerets, Brigitte
- 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
- Piedmonte, Marion
- Friedlander, Michael L
- Rodriguez, Gustavo C
- Copeland, Larry J
- de la Hoya, Miguel
- Perez Segura, Pedro
- Nevanlinna, Heli
- Aittomäki, Kristiina
- van Os, Theo A M
- Meijers-Heijboer, Hanne E J
- Van der Hout, Annemarie H
- Vreeswijk, Maaike P G
- Hoogerbrugge, Nicoline
- Ausems, Margreet G E M
- Van Doorn, Helena C
- Collée, J Margriet
- Olah, Edith
- DĂez, Orland
- Blanco, Ignacio
- Lazaro, Conxi
- Brunet, Joan
- FeliubadalĂł, LĂdia
- 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
- Zhang, Liying
- Joseph, Vijai
- Berger, Andreas
- Singer, Christian F
- Rappaport, Christine
- Geschwantler Kaulich, Daphne
- 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
- Stenmark Askmalm, Marie
- Borg, Ake
- Kuchenbaecker, Karoline B
- McGuffog, Lesley
- Barrowdale, Daniel
- Healey, Sue
- Lee, Andrew
- Pharoah, Paul D P
- Chenevix-Trench, Georgia
- Antoniou, Antonis C
- Friedman, Eitan