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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

Mulligan, Anna Marie; Couch, Fergus J.; Barrowdale, Daniel; Domchek, Susan M.; Eccles, Diana; Nevanlinna, Heli; Ramus, Susan J.; Robson, Mark; Sherman, Mark and Spurdle, Amanda B., et al. (2011) In Breast Cancer Research 13(6).
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.... (More)
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 x 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. (Less)
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Breast Cancer Research
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13
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6
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BioMed Central
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  • wos:000301173700002
  • scopus:80055117035
ISSN
1465-5411
DOI
10.1186/bcr3052
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English
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yes
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22a9b10e-ae86-4ff6-b79d-81b0ec613513 (old id 2493708)
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@article{22a9b10e-ae86-4ff6-b79d-81b0ec613513,
  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 x 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.},
  author       = {Mulligan, Anna Marie and Couch, Fergus J. and Barrowdale, Daniel and Domchek, Susan M. and Eccles, Diana and Nevanlinna, Heli and Ramus, Susan J. and Robson, Mark and Sherman, Mark and Spurdle, Amanda B. and Wappenschmidt, Barbara and Lee, Andrew and McGuffog, Lesley and Healey, Sue and Sinilnikova, Olga M. and Janavicius, Ramunas and Hansen, Thomas V. O. and Nielsen, Finn C. and Ejlertsen, Bent and Osorio, Ana and Munoz-Repeto, Ivan and Duran, Mercedes and Godino, Javier and Pertesi, Maroulio and Benitez, Javier and Peterlongo, Paolo and Manoukian, Siranoush and Peissel, Bernard and Zaffaroni, Daniela and Cattaneo, Elisa and Bonanni, Bernardo and Viel, Alessandra and Pasini, Barbara and Papi, Laura and Ottini, Laura and Savarese, Antonella and Bernard, Loris and Radice, Paolo and Hamann, Ute and Verheus, Martijn and Meijers-Heijboer, Hanne E. J. and Wijnen, Juul and Garcia, Encarna B. Gomez and Nelen, Marcel R. and Kets, C. Marleen and Seynaeve, Caroline and Tilanus-Linthorst, Madeleine M. A. and van der Luijt, Rob B. and van Os, Theo and Rookus, Matti and Frost, Debra and Jones, J. Louise and Evans, D. Gareth and Lalloo, Fiona and Eeles, Ros and Izatt, Louise and Adlard, Julian and Davidson, Rosemarie and Cook, Jackie and Donaldson, Alan and Dorkins, Huw and Gregory, Helen and Eason, Jacqueline and Houghton, Catherine and Barwell, Julian and Side, Lucy E. and McCann, Emma and Murray, Alex and Peock, Susan and Godwin, Andrew K. and Schmutzler, Rita K. and Rhiem, Kerstin and Engel, Christoph and Meindl, Alfons and Ruehl, Ina and Arnold, Norbert and Niederacher, Dieter and Sutter, Christian and Deissler, Helmut and Gadzicki, Dorothea and Kast, Karin and Preisler-Adams, Sabine and Varon-Mateeva, Raymonda and Schoenbuchner, Ines and Fiebig, Britta and Heinritz, Wolfram and Schaefer, Dieter and Gevensleben, Heidrun and Caux-Moncoutier, Virginie and Fassy-Colcombet, Marion and Cornelis, Francois and Mazoyer, Sylvie and Leone, Melanie and Boutry-Kryza, Nadia and Hardouin, Agnes and Berthet, Pascaline and Muller, Daniele and Fricker, Jean-Pierre and Mortemousque, Isabelle and Pujol, Pascal and Coupier, Isabelle and Lebrun, Marine and Kientz, Caroline and Longy, Michel and Sevenet, Nicolas and Stoppa-Lyonnet, Dominique and Isaacs, Claudine and Caldes, Trinidad and de la Hoya, Miguel and Heikkinen, Tuomas and Aittomaki, Kristiina and Blanco, Ignacio and Lazaro, Conxi and Barkardottir, Rosa B. and Soucy, Penny and Dumont, Martine and Simard, Jacques and Montagna, Marco and Tognazzo, Silvia and D'Andrea, Emma and Fox, Stephen and Yan, Max and Rebbeck, Tim and Olopade, Olufunmilayo I. and Weitzel, Jeffrey N. and Lynch, Henry T. and Ganz, Patricia A. and Tomlinson, Gail E. and Wang, Xianshu and Fredericksen, Zachary and Pankratz, Vernon S. and Lindor, Noralane M. and Szabo, Csilla and Offit, Kenneth and Sakr, Rita and Gaudet, Mia and Bhatia, Jasmine and Kauff, Noah and Singer, Christian F. and Tea, Muy-Kheng and Gschwantler-Kaulich, Daphne and Fink-Retter, Anneliese and Mai, Phuong L. and Greene, Mark H. and Imyanitov, Evgeny and O'Malley, Frances P. and Ozcelik, Hilmi and Glendon, Gordon and Toland, Amanda E. and Gerdes, Anne-Marie and Thomassen, Mads and Kruse, Torben A. and Jensen, Uffe Birk and Skytte, Anne-Bine and Caligo, Maria A. and Soller, Maria and Henriksson, Karin and Wachenfeldt, von Anna and Arver, Brita and Stenmark-Askmalm, Marie and Karlsson, Per and Ding, Yuan Chun and Neuhausen, Susan L. and Beattie, Mary and Pharoah, Paul D. P. and Moysich, Kirsten B. and Nathanson, Katherine L. and Karlan, Beth Y. and Gross, Jenny and John, Esther M. and Daly, Mary B. and Buys, Saundra M. and Southey, Melissa C. and Hopper, John L. and Terry, Mary Beth and Chung, Wendy and Miron, Alexander F. and Goldgar, David and Chenevix-Trench, Georgia and Easton, Douglas F. and Andrulis, Irene L. and Antoniou, Antonis C.},
  issn         = {1465-5411},
  language     = {eng},
  number       = {6},
  publisher    = {BioMed Central},
  series       = {Breast Cancer Research},
  title        = {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},
  url          = {http://dx.doi.org/10.1186/bcr3052},
  volume       = {13},
  year         = {2011},
}