Common breast cancer susceptibility alleles are associated with tumor subtypes in BRCA1 and BRCA2 mutation carriers: results from the Consortium of Investigators of Modifiers of BRCA1/2.
Authors
Mulligan, Anna Marie
Couch, Fergus J
Barrowdale, Daniel
Domchek, Susan M
Eccles, Diana
Nevanlinna, Heli
Ramus, Susan J
Robson, Mark
Sherman, Mark
Spurdle, Amanda B
Wappenschmidt, Barbara
Family, Registry Breast Cancer
Embrace,
Collaborators, GEMO Study
Hebon,
Network, Ontario Cancer Genetics
Swe-brca,
Cimba,
Osorio, Ana
Munoz-Repeto, Ivan
Coupier, Isabelle
Duran, Mercedes
Godino, Javier
Pertesi, Maroulio
Benitez, Javier
Peterlongo, Paolo
Manoukian, Siranoush
Peissel, Bernard
Zaffaroni, Daniela
Cattaneo, Elisa
Bonanni, Bernardo
Lebrun, Marine
Viel, Alessandra
Pasini, Barbara
Papi, Laura
Ottini, Laura
Savarese, Antonella
Bernard, Loris
Radice, Paolo
Hamann, Ute
Verheus, Martijn
Meijers-Heijboer, Hanne EJ
Kientz, Caroline
Wijnen, Juul
Gomez, Garcia Encarna B
Nelen, Marcel R
Kets, C Marleen
Seynaeve, Caroline
Tilanus-Linthorst, Madeleine MA
van, der Luijt Rob B
van, Os Theo A
Rookus, Matti
Frost, Debra
Longy, Michel
Jones, J Louise
Evans, D Gareth
Lalloo, Fiona
Eeles, Ros
Izatt, Louise
Adlard, Julian
Davidson, Rosemarie
Cook, Jackie
Donaldson, Alan
Dorkins, Huw
Sevenet, Nicolas
Gregory, Helen
Eason, Jacqueline
Houghton, Catherine
Barwell, Julian
Side, Lucy E
McCann, Emma
Murray, Alex
Peock, Susan
Godwin, Andrew
Schmutzler, Rita K
Stoppa-Lyonnet, Dominique
Rhiem, Kerstin
Engel, Christoph
Meindl, Alfons
Ruehl, Ina
Arnold, Norbert
Niederacher, Dieter
Sutter, Christian
Deissler, Helmut
Gadzicki, Dorothea
Kast, Karin
Isaacs, Claudine
Preisler-Adams, Sabine
Varon-Mateeva, Raymonda
Schoenbuchner, Ines
Fiebig, Britta
Heinritz, Wolfram
Schafer, Dieter
Gevensleben, Heidrun
Caux-Moncoutier, Virginie
Fassy-Colcombet, Marion
Cornelis, Francois
Caldes, Trinidad
Mazoyer, Sylvie
Leone, Melanie
Boutry-Kryza, Nadia
Hardouin, Agnes
Berthet, Pascaline
Muller, Daniele
Fricker, Jean-Pierre
Mortemousque, Isabelle
Pujol, Pascal
de, al Hoya Miguel
Heikkinen, Tuomas
Aittomaki, Kristiina
Blanco, Ignacio
Lazaro, Conxi
Barkardottir, Rosa B
Soucy, Penny
Dumont, Martine
Simard, Jacques
Montagna, Marco
Tognazzo, Silvia
D'Andrea, Emma
McGuffog, Lesley
Fox, Stephen
Yan, Max
Rebbeck, Timothy R
Olopade, Olufunmilayo I
Weitzel, Jeffrey N
Lynch, Henry T
Ganz, Patricia A
Tomlinson, Gail E
Wang, Xianshu
Fredericksen, Zachary
Healey, Sue
Pankratz, Vernon S
Lindor, Noralane M
Szabo, Csila
Offit, Kenneth
Sakr, Rita
Gaudet, Mia
Bhatia, Jasmine
Kauff, Noah
Singer, Christian F
Tea, Muy-Kheng
Sinilnikova, Olga M
Gschwantler-Kaulich, Daphne
Fink-Retter, Anneliese
Mai, Phuong L
Greene, Mark H
Imyanitov, Evgeny
O'Malley, Frances P
Ozcelik, Hilmi
Glendon, Gordon
Toland, Amanda E
Gerdes, Anne-Marie
Janavicius, Ramunas
Thomassen, Mads
Kruse, Torben A
Birk, Jensen Uffe
Skytte, Anne-Bine
Caligo, Maria A
Soller, Maria
Henriksson, Karin
von, Wachenfeldt Anna
Arver, Brita
Stenmark-Askmalm, Marie
Hansen, Thomas VO
Karlsson, Per
Ding, Yuan Chun
Neuhausen, Susan L
Beattie, Mary
Moysich, Kirsten B
Nathanson, Katherine L
Karlan, Beth Y
Gross, Jenny
John, Esther M
Nielsen, Finn C
Daly, Mary B
Buys, Saundra M
Southey, Melissa C
Hopper, John L
Terry, Mary Beth
Chung, Wendy
Miron, Alexander F
Goldgar, David
Chenevix-Trench, Georgia
Ejlertsen, Bent
Andrulis, Irene L
Publication Date
2011-11-02ISSN
1465-542X
Type
Article
Metadata
Show full item recordCitation
Mulligan, A. M., Couch, F. J., Barrowdale, D., Domchek, S. M., Eccles, D., Nevanlinna, H., Ramus, S. J., et al. (2011). Common breast cancer susceptibility alleles are associated with tumor subtypes in BRCA1 and BRCA2 mutation carriers: results from the Consortium of Investigators of Modifiers of BRCA1/2.. http://www.dspace.cam.ac.uk/handle/1810/241605
Abstract
Abstract 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.
Sponsorship
National Cancer Institute (NCI) (R01CA128978)
EC FP7 CP (223175)
Cancer Research UK (CRUK-A10118)
Identifiers
This record's URL: http://www.dspace.cam.ac.uk/handle/1810/241605
Rights
Rights Holder: Mulligan et al.; licensee BioMed Central Ltd.
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