Common breast cancer susceptibility alleles are associated with tumour subtypes in BRCA1 and BRCA2 mutation carriers: results from the Consortium of Investigators of Modifiers of BRCA1/2
Creators: name: Mulligan, Anna
name: Couch, Fergus
name: Barrowdale, Daniel
name: Domchek, Susan
name: Eccles, Diana
name: Nevanlinna, Heli
name: Ramus, Susan
name: Robson, Mark
name: Sherman, Mark
name: Spurdle, Amanda
name: Wappenschmidt, Barbara
name: Lee, Andrew
name: McGuffog, Lesley
name: Healey, Sue
name: Sinilnikova, Olga
name: Janavicius, Ramunas
name: Hansen, Thomas
name: Nielsen, Finn
name: Ejlertsen, Bent
name: Osorio, Ana
name: Muñoz-Repeto, Ivan
name: Duran, Mercedes
name: Godino, Javier
name: Pertesi, Maroulio
name: Benítez, Javier
name: Peterlongo, Paolo
name: Manoukian, Siranoush
name: Peissel, Bernard
name: Zaffaroni, Daniela
name: Cattaneo, Elisa
name: Bonanni, Bernardo
name: Viel, Alessandra
name: Pasini, Barbara
name: Papi, Laura
name: Ottini, Laura
name: Savarese, Antonella
name: Bernard, Loris
name: Radice, Paolo
name: Hamann, Ute
name: Verheus, Martijn
name: Meijers-Heijboer, Hanne
name: Wijnen, Juul
name: Gómez García, Encarna
name: Nelen, Marcel
name: Kets, C Marleen
name: Seynaeve, Caroline
name: Tilanus-Linthorst, Madeleine
name: Van Der Luijt, Rob
name: Os, Theo
name: Rookus, Matti
name: Frost, Debra
name: Jones, J. Louise
name: Evans, D. Gareth
name: Lalloo, Fiona
name: Eeles, Ros
name: Izatt, Louise
name: Adlard, Julian
name: Davidson, Rosemarie
name: Cook, Jackie
name: Donaldson, Alan
name: Dorkins, Huw
name: Gregory, Helen
name: Eason, Jacqueline
name: Houghton, Catherine
name: Barwell, Julian
name: Side, Lucy
name: McCann, Emma
name: Murray, Alex
name: Peock, Susan
name: Godwin, Andrew
name: Schmutzler, Rita
name: Rhiem, Kerstin
name: Engel, Christoph
name: Meindl, Alfons
name: Ruehl, Ina
name: Arnold, Norbert
name: Niederacher, Dieter
name: Sutter, Christian
name: Deissler, Helmut
name: Gadzicki, Dorothea
name: Kast, Karin
name: Preisler-Adams, Sabine
name: Varon-Mateeva, Raymonda
name: Schoenbuchner, Ines
name: Fiebig, Britta
name: Heinritz, Wolfram
name: Schäfer, Dieter
name: Gevensleben, Heidrun
name: Caux-Moncoutier, Virginie
name: Fassy-Colcombet, Marion
name: Cornelis, François
name: Mazoyer, Sylvie
name: Léoné, Mélanie
name: Boutry-Kryza, Nadia
name: Hardouin, Agnès
name: Berthet, Pascaline
name: Muller, Danièle
name: Fricker, Jean-Pierre
name: Mortemousque, Isabelle
name: Pujol, Pascal
name: Coupier, Isabelle
name: Lebrun, Marine
name: Kientz, Caroline
name: Longy, Michel
name: Sevenet, Nicolas
name: Stoppa-Lyonnet, Dominique
name: Isaacs, Claudine
name: Caldes, Trinidad
name: De La Hoya, Miguel
name: Heikkinen, Tuomas
name: Aittomäki, Kristiina
name: Blanco, Ignacio
name: Lazaro, Conxi
name: Barkardottir, Rosa
name: Soucy, Penny
name: Dumont, Martine
name: Simard, Jacques
name: Montagna, Marco
name: Tognazzo, Silvia
name: D'Andrea, Emma
name: Fox, Stephen
name: Yan, Max
name: Rebbeck, Tim
name: Olopade, Olufunmilayo
name: Weitzel, Jeffrey
name: Lynch, Henry
name: Ganz, Patricia
name: Tomlinson, Gail
name: Wang, Xianshu
name: Fredericksen, Zachary
name: Pankratz, Vernon
name: Lindor, Noralane
name: Szabo, Csilla
name: Offit, Kenneth
name: Sakr, Rita
name: Gaudet, Mia
name: Bhatia, Jasmine
name: Kauff, Noah
name: Singer, Christian
name: Tea, Muy-Kheng
name: Gschwantler-Kaulich, Daphne
name: Fink-Retter, Anneliese
name: Mai, Phuong
name: Greene, Mark
name: Imyanitov, Evgeny
name: O'Malley, Frances
name: Ozcelik, Hilmi
name: Glendon, Gordon
name: Toland, Amanda
name: Gerdes, Anne-Marie
name: Thomassen, Mads
name: Kruse, Torben
name: Jensen, Uffe
name: Skytte, Anne-Bine
name: Caligo, Maria
name: Soller, Maria
name: Henriksson, Karin
name: Wachenfeldt, Von Anna
name: Arver, Brita
name: Stenmark-Askmalm, Marie
name: Karlsson, Per
name: Ding, Yuan
name: Neuhausen, Susan
name: Beattie, Mary
name: Pharoah, Paul
name: Moysich, Kirsten
name: Nathanson, Katherine
name: Karlan, Beth
name: Gross, Jenny
name: John, Esther
name: Daly, Mary
name: Buys, Saundra
name: Southey, Melissa
name: Hopper, John
name: Terry, Mary Beth
name: Chung, Wendy K.
name: Miron, Alexander
name: Goldgar, David
name: Chenevix-Trench, Georgia
name: Easton, Douglas
name: Andrulis, Irene
name: Antoniou, Antonis
Publisher: name: Columbia University
Year: 2011
Subjects: subject: Mutation (Biology)
subject: Breast--Cancer
subject: Genetics
subject: FOS: Biological sciences
subject: Molecular biology

description: Introduction: Previous studies have demonstrated that common breast cancer susceptibility alleles are differentially associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers. It is currently unknown how these alleles are associated with different breast cancer subtypes in BRCA1 and BRCA2 mutation carriers defined by estrogen (ER) or progesterone receptor (PR) status of the tumour. Methods: We used genotype data on up to 11,421 BRCA1 and 7,080 BRCA2 carriers, of whom 4,310 had been affected with breast cancer and had information on either ER or PR status of the tumour, to assess the associations of 12 loci with breast cancer tumour characteristics. Associations were evaluated using a retrospective cohort approach. Results: The results suggested stronger associations with ER-positive breast cancer than ER-negative for 11 loci in both BRCA1 and BRCA2 carriers. Among BRCA1 carriers, single nucleotide polymorphism (SNP) rs2981582 (FGFR2) exhibited the biggest difference based on ER status (per-allele hazard ratio (HR) for ER-positive = 1.35, 95% CI: 1.17 to 1.56 vs HR = 0.91, 95% CI: 0.85 to 0.98 for ER-negative, P-heterogeneity = 6.5 × 10-6). In contrast, SNP rs2046210 at 6q25.1 near ESR1 was primarily associated with ER-negative breast cancer risk for both BRCA1 and BRCA2 carriers. In BRCA2 carriers, SNPs in FGFR2, TOX3, LSP1, SLC4A7/NEK10, 5p12, 2q35, and 1p11.2 were significantly associated with ER-positive but not ER-negative disease. Similar results were observed when differentiating breast cancer cases by PR status. Conclusions: The associations of the 12 SNPs with risk for BRCA1 and BRCA2 carriers differ by ER-positive or ER-negative breast cancer status. The apparent differences in SNP associations between BRCA1 and BRCA2 carriers, and non-carriers, may be explicable by differences in the prevalence of tumour subtypes. As more risk modifying variants are identified, incorporating these associations into breast cancer subtype-specific risk models may improve clinical management for mutation carriers.