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.
Original language | English |
---|---|
Article number | R110 |
Number of pages | 20 |
Journal | Breast Cancer Research |
Volume | 13 |
Issue number | 6 |
DOIs | |
Publication status | Published - 2 Nov 2011 |
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In: Breast Cancer Research, Vol. 13, No. 6, R110, 02.11.2011.
Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - Common breast cancer susceptibility alleles are associated with tumour subtypes in BRCA1 and BRCA2 mutation carriers
T2 - results from the Consortium of Investigators of Modifiers of BRCA1/2
AU - Mulligan, Anna M.
AU - Couch, Fergus J.
AU - Barrowdale, Daniel
AU - Domchek, Susan M.
AU - Eccles, Diana
AU - Nevanlinna, Heli
AU - Ramus, Susan J.
AU - Robson, Mark
AU - Sherman, Mark
AU - Spurdle, Amanda B.
AU - Wappenschmidt, Barbara
AU - Lee, Andrew
AU - McGuffog, Lesley
AU - Healey, Sue
AU - Sinilnikova, Olga M.
AU - Janavicius, Ramunas
AU - Hansen, Thomas V.
AU - Nielsen, Finn C.
AU - Ejlertsen, Bent
AU - Osorio, Ana
AU - Muñoz-Repeto, Iván
AU - Durán, Mercedes
AU - Godino, Javier
AU - Pertesi, Maroulio
AU - Benítez, Javier
AU - Peterlongo, Paolo
AU - Manoukian, Siranoush
AU - Peissel, Bernard
AU - Zaffaroni, Daniela
AU - Cattaneo, Elisa
AU - Bonanni, Bernardo
AU - Viel, Alessandra
AU - Pasini, Barbara
AU - Papi, Laura
AU - Ottini, Laura
AU - Savarese, Antonella
AU - Bernard, Loris
AU - Radice, Paolo
AU - Hamann, Ute
AU - Verheus, Martijn
AU - Meijers-Heijboer, Hanne E.J.
AU - Wijnen, Juul
AU - Gómez García, Encarna B.
AU - Nelen, Marcel R.
AU - Kets, C. Marleen
AU - Seynaeve, Caroline
AU - Tilanus-Linthorst, Madeleine M.A.
AU - van der Luijt, Rob B.
AU - Os, Theo V.
AU - Rookus, Matti
AU - Frost, Debra
AU - Jones, J. Louise
AU - Evans, D. Gareth
AU - Lalloo, Fiona
AU - Eeles, Ros
AU - Izatt, Louise
AU - Adlard, Julian
AU - Davidson, Rosemarie
AU - Cook, Jackie
AU - Donaldson, Alan
AU - Dorkins, Huw
AU - Gregory, Helen
AU - Eason, Jacqueline
AU - Houghton, Catherine
AU - Barwell, Julian
AU - Side, Lucy E.
AU - McCann, Emma
AU - Murray, Alex
AU - Peock, Susan
AU - Godwin, Andrew K.
AU - Schmutzler, Rita K.
AU - Rhiem, Kerstin
AU - Engel, Christoph
AU - Meindl, Alfons
AU - Ruehl, Ina
AU - Arnold, Norbert
AU - Niederacher, Dieter
AU - Sutter, Christian
AU - Deissler, Helmut
AU - Gadzicki, Dorothea
AU - Kast, Karin
AU - Preisler-Adams, Sabine
AU - Varon-Mateeva, Raymonda
AU - Schoenbuchner, Ines
AU - Fiebig, Britta
AU - Heinritz, Wolfram
AU - Schäfer, Dieter
AU - Gevensleben, Heidrun
AU - Caux-Moncoutier, Virginie
AU - Fassy-Colcombet, Marion
AU - Cornelis, François
AU - Mazoyer, Sylvie
AU - Léoné, Mélanie
AU - Boutry-Kryza, Nadia
AU - Hardouin, Agnès
AU - Berthet, Pascaline
AU - Muller, Danièle
AU - Fricker, Jean Pierre
AU - Mortemousque, Isabelle
AU - Pujol, Pascal
AU - Coupier, Isabelle
AU - Lebrun, Marine
AU - Kientz, Caroline
AU - Longy, Michel
AU - Sevenet, Nicolas
AU - Stoppa-Lyonnet, Dominique
AU - Isaacs, Claudine
AU - Caldes, Trinidad
AU - de la Hoya, Miguel
AU - Heikkinen, Tuomas
AU - Aittomäki, Kristiina
AU - Blanco, Ignacio
AU - Lazaro, Conxi
AU - Barkardottir, Rosa B.
AU - Soucy, Penny
AU - Dumont, Martine
AU - Simard, Jacques
AU - Montagna, Marco
AU - Tognazzo, Silvia
AU - D'Andrea, Emma
AU - Fox, Stephen
AU - Yan, Max
AU - Rebbeck, Tim
AU - Olopade, Olufunmilayo I.
AU - Weitzel, Jeffrey N.
AU - Lynch, Henry T.
AU - Ganz, Patricia A.
AU - Tomlinson, Gail E.
AU - Wang, Xianshu
AU - Fredericksen, Zachary
AU - Pankratz, Vernon S.
AU - Lindor, Noralane M.
AU - Szabo, Csilla
AU - Offit, Kenneth
AU - Sakr, Rita
AU - Gaudet, Mia
AU - Bhatia, Jasmine
AU - Kauff, Noah
AU - Singer, Christian F.
AU - Tea, Muy Kheng
AU - gschwantler-kaulich, Daphne
AU - Fink-Retter, Anneliese
AU - Mai, Phuong L.
AU - Greene, Mark H.
AU - Imyanitov, Evgeny
AU - O'Malley, Frances P.
AU - Ozcelik, Hilmi
AU - Glendon, Gordon
AU - Toland, Amanda E.
AU - Gerdes, Anne Marie
AU - Thomassen, Mads
AU - Kruse, Torben A.
AU - Jensen, Uffe B.
AU - Skytte, Anne Bine
AU - Caligo, Maria A.
AU - Soller, Maria
AU - Henriksson, Karin
AU - Wachenfeldt, von Anna
AU - Arver, Brita
AU - Stenmark-Askmalm, Marie
AU - Karlsson, Per
AU - Ding, Yuan C.
AU - Neuhausen, Susan L.
AU - Beattie, Mary
AU - Pharoah, Paul D.P.
AU - Moysich, Kirsten B.
AU - Nathanson, Katherine L.
AU - Karlan, Beth Y.
AU - Gross, Jenny
AU - John, Esther M.
AU - Daly, Mary B.
AU - Buys, Saundra M.
AU - Southey, Melissa C.
AU - Hopper, John L.
AU - Terry, Mary B.
AU - Chung, Wendy
AU - Miron, Alexander F.
AU - Goldgar, David
AU - Chenevix-Trench, Georgia
AU - Easton, Douglas F.
AU - Andrulis, Irene L.
AU - Antoniou, Antonis C.
AU - HeBon
PY - 2011/11/2
Y1 - 2011/11/2
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=80055117035&partnerID=8YFLogxK
U2 - 10.1186/bcr3052
DO - 10.1186/bcr3052
M3 - Article
C2 - 22053997
AN - SCOPUS:80055117035
SN - 1465-5411
VL - 13
JO - Breast Cancer Research
JF - Breast Cancer Research
IS - 6
M1 - R110
ER -