Common Breast Cancer Susceptibility Alleles and the Risk of Breast Cancer for BRCA1 and BRCA2 Mutation Carriers: Implications for Risk Prediction
Creators: name: Noguchi, Tetsuro
name: Caldes, Trinidad
name: Caligo, Maria
name: Viel, Alessandra
name: Ramus, Susan J.
name: Claes, Kathleen
name: Aalfs, Cora M.
name: Kaufman, Bella
name: Friedman, Eitan
name: Manoukian, Siranoush
name: Jernström, Helena
name: Milgrom, Roni
name: Schönbuchner, Ines
name: Cole, Trevor
name: Allavena, Anna
name: Isaacs, Claudine
name: Lazaro, Conxi
name: Chen, Xiaoqing
name: Buys, Saundra S.
name: Porteous, Mary E.
name: Hansen, Thomas V.O.
name: Wang, Xianshu
name: Hardouin, Agnès
name: Arnold, Norbert
name: Benitez, Javier
name: Engel, Christoph
name: Simard, Jacques
name: Cook, Jackie
name: Jensen, Uffe Birk
name: Preisler-Adams, Sabine
name: Rantala, Johanna
name: Walker, Lisa
name: Meindl, Alfons
name: Montagna, Marco
name: Beesley, Jonathan
name: Aittomäki, Kristiina
name: Terry, Mary B.
name: Vénat-Bouvet, Laurence
name: Faivre, Laurence
name: Miron, Alexander
name: Domchek, Susan
name: McGuffog, Lesley
name: Zikan, Michal
name: Godino, Javier
name: Neuhausen, Susan L.
name: Lindblom, Annika
name: Nathanson, Kate
name: Van Der Luijt, Rob B.
name: Meijers-Heijboer, E. J.
name: Hamann, Ute
name: Mazoyer, Sylvie
name: Davidson, Rosemarie
name: Hogervorst, Frans
name: Spurdle, Amanda B.
name: Lalloo, Fiona
name: Rennert, Gad
name: Niederacher, Dieter
name: Zaffaroni, Daniela
name: Blanco, Ignacio
name: Wappenschmidt, Barbara
name: Szabo, Csilla I.
name: Gadzicki, Dorothea
name: Dubrovsky, Maya
name: Peock, Susan
name: Dutra-Clarke, Ana
name: Ganz, Patricia A.
name: Peterlongo, Paolo
name: Weitzel, Jeffrey N.
name: Poppe, Bruce
name: Rodriguez, Gustavo C.
name: Lasset, Christine
name: Bonadona, Valérie
name: Mai, Phuong L.
name: Dorkins, Huw
name: Lubinski, Jan
name: Glendon, Gord
name: Holland, Helene
name: Frénay, Marc
name: Rebbeck, Timothy R.
name: Hopper, John L.
name: Blok, Marinus J.
name: Offit, Kenneth
name: Borg, Ake
name: Lejbkowicz, Flavio
name: Devilee, Peter
name: Frost, Debra
name: Blank, Stephanie V.
name: Kirchhoff, Tomas
name: Van Asperen, Christi J.
name: Agnarsson, Bjarni A.
name: Foretova, Lenka
name: Deissler, Helmut
name: Lindor, Noralane M.
name: Nevanlinna, Heli
name: Kriege, Mieke
name: Toland, Amanda Ewart
name: Gschwantler-Kaulich, Daphne
name: Rouleau, Etienne
name: De Pauw, Antoine
name: Karlan, Beth Y.
name: Goldgar, David
name: Oliver, Clare
name: Godwin, Andrew K.
name: Olopade, Olufunmilayo I.
name: Osorio, Ana
name: Easton, Douglas F.
name: Cohen, Shimrit
name: Berthet, Pascaline
name: Tihomirova, Laima
name: Platte, Radka
name: Lasa, Adriana
name: Rookus, Matti
name: Conroy, Don
name: Couch, Fergus J.
name: Loustalot, Catherine
name: Sobol, Hagay
name: Chenevix-Trench, Georgia
name: Piedmonte, Marion
name: Schwartz, Peter E.
name: Imyanitov, Evgeny
name: Heidemann, Simone
name: Barile, Monica
name: Casella, Cinzia
name: Jnson, Lars
name: Laitman, Yael
name: Healey, Sue
name: Schmutzler, Rita
name: Cruger, Dorthe
name: Sunde, Lone
name: Ding, Yuan Chun
name: Nogues, Catherine
name: Dall'Olio, Valentina
name: Yassin, Yosuf
name: Antoniou, Antonis C.
name: Leroux, Dominique
name: Sutter, Christian
name: Evans, D. Gareth
name: Huzarski, Tomasz
name: Daly, Mary B.
name: Pichert, Gabriella
name: Lochmann, Magdalena
name: Kast, Karin
name: Gross, Jenny
name: Stoppa-Lyonnet, Dominique
name: Andrulis, Irene L.
name: Melin, Beatrice
name: Dreyfus, Hélène
name: Stenmark-Askmalm, Marie
name: Gerdes, Anne Marie
name: Boggess, John F.
name: Paterson, Joan
name: Kennedy, M. John
name: Thomassen, Mads
name: Pfeiler, Georg
name: Basil, Jack
name: Devlin, Vincent
name: Tejada, Maria Isabel
name: Hoogerbrugge, Nicoline
name: Cook, Margaret
name: De La Hoya, Miguel
name: Pankratz, Vernon S.
name: Sucheston, Lara
name: Radice, Paolo
name: John, Esther M.
name: Singer, Christian F.
name: Peissel, Bernard
name: Lynch, Henry T.
name: Varon-Mateeva, Raymonda
name: Hodgson, Shirley
name: Durán, Mercedes
name: Greene, Mark H.
name: Wakeley, Katie
name: Sinilnikova, Olga M.
name: Dressler, Anne Catharina
name: Ozcelik, Hilmi
name: Morrison, Patrick J.
name: Jakubowska, Ania
name: Tomlinson, Gail
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2010

description: The known breast cancer (BC) susceptibility polymorphisms in FGFR2, TNRC9/TOX3, MAP3K1,LSP1 and 2q35 confer increased risks of BC for BRCA1 or BRCA2 mutation carriers. We evaluated the associations of three additional SNPs, rs4973768 in SLC4A7/NEK10, rs6504950 in STXBP4/COX11 and rs10941679 at 5p12 and reanalyzed the previous associations using additional carriers in a sample of 12,525 BRCA1 and 7,409 BRCA2 carriers. Additionally, we investigated potential interactions between SNPs and assessed the implications for risk prediction. The minor alleles of rs4973768 and rs10941679 were associated with increased BC risk for BRCA2 carriers (per-allele Hazard Ratio (HR)=1.10, 95%CI:1.03-1.18, p=0.006 and HR=1.09, 95%CI:1.01-1.19, p=0.03, respectively). Neither SNP was associated with BC risk for BRCA1 carriers and rs6504950 was not associated with BC for either BRCA1 or BRCA2 carriers. Of the nine polymorphisms investigated, seven were associated with BC for BRCA2 carriers (FGFR2, TOX3, MAP3K1, LSP1, 2q35, SLC4A7, 5p12, p-values:7×10−11-0.03), but only TOX3 and 2q35 were associated with the risk for BRCA1 carriers (p=0.0049, 0.03 respectively). All risk associated polymorphisms appear to interact multiplicatively on BC risk for mutation carriers. Based on the joint genotype distribution of the seven risk associated SNPs in BRCA2 mutation carriers, the 5% of BRCA2 carriers at highest risk (i.e. between 95th and 100th percentiles) were predicted to have a probability between 80% and 96% of developing BC by age 80, compared with 42-50% for the 5% of carriers at lowest risk. Our findings indicated that these risk differences may be sufficient to influence the clinical management of mutation carriers.