Abstract
| Original language | English |
|---|---|
| Article number | e1003212 |
| Pages (from-to) | e1003212 |
| Journal | PLOS Genetics |
| Volume | 9 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 2013 |
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In: PLOS Genetics, Vol. 9, No. 3, e1003212, 2013, p. e1003212.
Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - Genome-wide association study in BRCA1 mutation carriers identifies novel loci associated with breast and ovarian cancer risk
AU - Couch, Fergus J.
AU - Wang, Xianshu
AU - McGuffog, Lesley
AU - Lee, Andrew
AU - Olswold, Curtis
AU - Kuchenbaecker, Karoline B.
AU - Soucy, Penny
AU - Fredericksen, Zachary
AU - Barrowdale, Daniel
AU - Dennis, Joe
AU - Gaudet, Mia M.
AU - Dicks, Ed
AU - Kosel, Matthew
AU - Healey, Sue
AU - Sinilnikova, Olga M.
AU - Lee, Adam
AU - Bacot, François
AU - Vincent, Daniel
AU - Hogervorst, Frans B. L.
AU - Peock, Susan
AU - Stoppa-Lyonnet, Dominique
AU - Jakubowska, Anna
AU - Radice, Paolo
AU - Schmutzler, Rita Katharina
AU - Domchek, Susan M.
AU - Piedmonte, Marion
AU - Singer, Christian F.
AU - Friedman, Eitan
AU - Thomassen, Mads
AU - Hansen, Thomas V. O.
AU - Neuhausen, Susan L.
AU - Szabo, Csilla I.
AU - Blanco, Ignacio
AU - Greene, Mark H.
AU - Karlan, Beth Y.
AU - Garber, Judy
AU - Phelan, Catherine M.
AU - Weitzel, Jeffrey N.
AU - Montagna, Marco
AU - Olah, Edith
AU - Andrulis, Irene L.
AU - Godwin, Andrew K.
AU - Yannoukakos, Drakoulis
AU - Goldgar, David E.
AU - Caldes, Trinidad
AU - Nevanlinna, Heli
AU - Osorio, Ana
AU - Terry, Mary Beth
AU - Daly, Mary B.
AU - van Rensburg, Elizabeth J.
AU - Hamann, Ute
AU - Ramus, Susan J.
AU - Toland, Amanda Ewart
AU - Caligo, Maria A.
AU - Olopade, Olufunmilayo I.
AU - Tung, Nadine
AU - Claes, Kathleen
AU - Beattie, Mary S.
AU - Southey, Melissa C.
AU - Imyanitov, Evgeny N.
AU - Tischkowitz, Marc
AU - Janavicius, Ramunas
AU - John, Esther M.
AU - Kwong, Ava
AU - Diez, Orland
AU - Balmaña, Judith
AU - Barkardottir, Rosa B.
AU - Arun, Banu K.
AU - Rennert, Gad
AU - teo, Soo-Hwang
AU - Ganz, Patricia A.
AU - Campbell, Ian
AU - van der Hout, Annemarie H.
AU - van Deurzen, Carolien H. M.
AU - Seynaeve, Caroline
AU - Gómez Garcia, Encarna B.
AU - van Leeuwen, Flora E.
AU - Meijers-Heijboer, Hanne E. J.
AU - Gille, Johannes J. P.
AU - Ausems, Margreet G. E. M.
AU - Blok, Marinus J.
AU - Ligtenberg, Marjolijn J. L.
AU - Rookus, Matti A.
AU - Devilee, Peter
AU - Verhoef, Senno
AU - van Os, Theo A. M.
AU - Wijnen, Juul T.
AU - Frost, Debra
AU - Ellis, Steve
AU - Fineberg, Elena
AU - Platte, Radka
AU - Evans, D. Gareth
AU - Izatt, Louise
AU - Eeles, Rosalind A.
AU - Adlard, Julian
AU - Eccles, Diana M.
AU - Cook, Jackie
AU - Brewer, Carole
AU - Douglas, Fiona
AU - Hodgson, Shirley
AU - Morrison, Patrick J.
AU - Side, Lucy E.
AU - Donaldson, Alan
AU - Houghton, Catherine
AU - Rogers, Mark T.
AU - Dorkins, Huw
AU - Eason, Jacqueline
AU - Gregory, Helen
AU - McCann, Emma
AU - Murray, Alex
AU - Calender, Alain
AU - Hardouin, Agnès
AU - Berthet, Pascaline
AU - Delnatte, Capucine
AU - Nogues, Catherine
AU - Lasset, Christine
AU - Houdayer, Claude
AU - Leroux, Dominique
AU - Rouleau, Etienne
AU - Prieur, Fabienne
AU - Damiola, Francesca
AU - Sobol, Hagay
AU - Coupier, Isabelle
AU - Venat-Bouvet, Laurence
AU - Castera, Laurent
AU - Gauthier-Villars, Marion
AU - Léoné, Mélanie
AU - Pujol, Pascal
AU - Mazoyer, Sylvie
AU - Bignon, Yves-Jean
AU - Złowocka-Perłowska, Elżbieta
AU - Gronwald, Jacek
AU - Lubinski, Jan
AU - Durda, Katarzyna
AU - Jaworska, Katarzyna
AU - Huzarski, Tomasz
AU - Spurdle, Amanda B.
AU - Viel, Alessandra
AU - Peissel, Bernard
AU - Bonanni, Bernardo
AU - Melloni, Giulia
AU - Ottini, Laura
AU - Papi, Laura
AU - Varesco, Liliana
AU - Tibiletti, Maria Grazia
AU - Peterlongo, Paolo
AU - Volorio, Sara
AU - Manoukian, Siranoush
AU - Pensotti, Valeria
AU - Arnold, Norbert
AU - Engel, Christoph
AU - Deissler, Helmut
AU - Gadzicki, Dorothea
AU - Gehrig, Andrea
AU - Kast, Karin
AU - Rhiem, Kerstin
AU - Meindl, Alfons
AU - Niederacher, Dieter
AU - Ditsch, Nina
AU - Plendl, Hansjoerg
AU - Preisler-Adams, Sabine
AU - Engert, Stefanie
AU - Sutter, Christian
AU - Varon-Mateeva, Raymonda
AU - Wappenschmidt, Barbara
AU - Weber, Bernhard H. F.
AU - Arver, Brita
AU - Stenmark-Askmalm, Marie
AU - Loman, Niklas
AU - Rosenquist, Richard
AU - Einbeigi, Zakaria
AU - Nathanson, Katherine L.
AU - Rebbeck, Timothy R.
AU - Blank, Stephanie V.
AU - Cohn, David E.
AU - Rodriguez, Gustavo C.
AU - Small, Laurie
AU - Friedlander, Michael
AU - Bae-Jump, Victoria L.
AU - Fink-Retter, Anneliese
AU - Rappaport, Christine
AU - Gschwantler-Kaulich, Daphne
AU - Pfeiler, Georg
AU - tea, Muy-Kheng
AU - Lindor, Noralane M.
AU - Kaufman, Bella
AU - Shimon Paluch, Shani
AU - Laitman, Yael
AU - Skytte, Anne-Bine
AU - Gerdes, Anne-Marie
AU - Pedersen, Inge Sokilde
AU - Moeller, Sanne Traasdahl
AU - Kruse, Torben A.
AU - Jensen, Uffe Birk
AU - Vijai, Joseph
AU - Sarrel, Kara
AU - Robson, Mark
AU - Kauff, Noah
AU - Mulligan, Anna Marie
AU - Glendon, Gord
AU - Ozcelik, Hilmi
AU - Ejlertsen, Bent
AU - Nielsen, Finn C.
AU - Jønson, Lars
AU - Andersen, Mette K.
AU - Ding, Yuan Chun
AU - Steele, Linda
AU - Foretova, Lenka
AU - Teulé, Alex
AU - Lazaro, Conxi
AU - Brunet, Joan
AU - Pujana, Miquel Angel
AU - Mai, Phuong L.
AU - Loud, Jennifer T.
AU - Walsh, Christine
AU - Lester, Jenny
AU - Orsulic, Sandra
AU - Narod, Steven A.
AU - Herzog, Josef
AU - Sand, Sharon R.
AU - Tognazzo, Silvia
AU - Agata, Simona
AU - Vaszko, Tibor
AU - Weaver, Joellen
AU - Stavropoulou, Alexandra V.
AU - Buys, Saundra S.
AU - Romero, Atocha
AU - de la Hoya, Miguel
AU - Aittomäki, Kristiina
AU - Muranen, Taru A.
AU - Duran, Mercedes
AU - Chung, Wendy K.
AU - Lasa, Adriana
AU - Dorfling, Cecilia M.
AU - Miron, Alexander
AU - Benitez, Javier
AU - Senter, Leigha
AU - Huo, Dezheng
AU - Chan, Salina B.
AU - Sokolenko, Anna P.
AU - Chiquette, Jocelyne
AU - Tihomirova, Laima
AU - Friebel, Tara M.
AU - Agnarsson, Bjarni A.
AU - Lu, Karen H.
AU - Lejbkowicz, Flavio
AU - James, Paul A.
AU - Hall, Per
AU - Dunning, Alison M.
AU - Tessier, Daniel
AU - Cunningham, Julie
AU - Slager, Susan L.
AU - Wang, Chen
AU - Hart, Steven
AU - Stevens, Kristen
AU - Simard, Jacques
AU - Pastinen, Tomi
AU - Pankratz, Vernon S.
AU - Offit, Kenneth
AU - Easton, Douglas F.
AU - Chenevix-Trench, Georgia
AU - Antoniou, Antonis C.
PY - 2013
Y1 - 2013
N2 - BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7 × 10(-8), HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4 × 10(-8), HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4 × 10(-8), HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific association. The 17q21.31 locus was also associated with ovarian cancer risk in 8,211 BRCA2 carriers (P = 2×10(-4)). These loci may lead to an improved understanding of the etiology of breast and ovarian tumors in BRCA1 carriers. Based on the joint distribution of the known BRCA1 breast cancer risk-modifying loci, we estimated that the breast cancer lifetime risks for the 5% of BRCA1 carriers at lowest risk are 28%-50% compared to 81%-100% for the 5% at highest risk. Similarly, based on the known ovarian cancer risk-modifying loci, the 5% of BRCA1 carriers at lowest risk have an estimated lifetime risk of developing ovarian cancer of 28% or lower, whereas the 5% at highest risk will have a risk of 63% or higher. Such differences in risk may have important implications for risk prediction and clinical management for BRCA1 carriers
AB - BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7 × 10(-8), HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4 × 10(-8), HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4 × 10(-8), HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific association. The 17q21.31 locus was also associated with ovarian cancer risk in 8,211 BRCA2 carriers (P = 2×10(-4)). These loci may lead to an improved understanding of the etiology of breast and ovarian tumors in BRCA1 carriers. Based on the joint distribution of the known BRCA1 breast cancer risk-modifying loci, we estimated that the breast cancer lifetime risks for the 5% of BRCA1 carriers at lowest risk are 28%-50% compared to 81%-100% for the 5% at highest risk. Similarly, based on the known ovarian cancer risk-modifying loci, the 5% of BRCA1 carriers at lowest risk have an estimated lifetime risk of developing ovarian cancer of 28% or lower, whereas the 5% at highest risk will have a risk of 63% or higher. Such differences in risk may have important implications for risk prediction and clinical management for BRCA1 carriers
U2 - https://doi.org/10.1371/journal.pgen.1003212
DO - https://doi.org/10.1371/journal.pgen.1003212
M3 - Article
C2 - 23544013
SN - 1553-7390
VL - 9
SP - e1003212
JO - PLoS Genetics
JF - PLoS Genetics
IS - 3
M1 - e1003212
ER -