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

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

doi:http://dx.doi.org/10.1186/bcr3052

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

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

53 Citations (Scopus)

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
Journal	Breast Cancer Research (Online Edition)
Volume	13
Issue number	6
Pages (from-to)	R110
ISSN	1465-5411
DOIs	https://doi.org/10.1186/bcr3052
Publication status	Published - 2 Nov 2011

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Cite this

Mulligan, A. M., Couch, F. J., Barrowdale, D., Domchek, S. M., Eccles, D., Nevanlinna, H., Ramus, S. J., Robson, M., Sherman, M., Spurdle, A. B., Wappenschmidt, B., Lee, A. R., McGuffog, L., Healey, S., Sinilnikova, O. M., Janavicius, R., Hansen, T. V. O., Nielsen, F. C., Ejlertsen, B., ... Cimba (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. Breast Cancer Research (Online Edition), 13(6), R110. https://doi.org/10.1186/bcr3052

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. / Mulligan, Anna Marie; Couch, Fergus J; Barrowdale, Daniel et al.

In: Breast Cancer Research (Online Edition), Vol. 13, No. 6, 02.11.2011, p. R110.

Research output: Contribution to journal › Journal article › Research › peer-review

Mulligan, AM, Couch, FJ, Barrowdale, D, Domchek, SM, Eccles, D, Nevanlinna, H, Ramus, SJ, Robson, M, Sherman, M, Spurdle, AB, Wappenschmidt, B, Lee, AR, McGuffog, L, Healey, S, Sinilnikova, OM, Janavicius, R, Hansen, TVO, Nielsen, FC, Ejlertsen, B, Osorio, A, Munoz-Repeto, I, Duran, M, Godino, J, Pertesi, M, Benitez, J, Peterlongo, P, Manoukian, S, Peissel, B, Zaffaroni, D, Cattaneo, E, Bonanni, B, Viel, A, Pasini, B, Papi, L, Ottini, L, Savarese, A, Bernard, L, Radice, P, Hamann, U, Verheus, M, Meijers-Heijboer, HE, Wijnen, J, Gomez Garcia, EB, Nelen, MR, Kets, CM, Seynaeve, C, Tilanus-Linthorst, MM, van der Luijt, RB, van Os, T, Rookus, M, Frost, D, Jones, JL, Evans, DG, Lalloo, F, Eeles, R, Izatt, L, Adlard, J, Davidson, R, Cook, J, Donaldson, A, Dorkins, H, Gregory, H, Eason, J, Houghton, C, Barwell, J, Side, LE, McCann, E, Murray, A, Peock, S, Godwin, A, Schmutzler, RK, Rhiem, K, Engel, C, Meindl, A, Ruehl, I, Arnold, N, Niederacher, D, Sutter, C, Deissler, H, Gadzicki, D, Kast, K, Preisler-Adams, S, Varon-Mateeva, R, Schoenbuchner, I, Fiebig, B, Heinritz, W, Schafer, D, Gevensleben, H, Caux-Moncoutier, V, Fassy-Colcombet, M, Cornelis, F, Mazoyer, S, Leone, M, Boutry-Kryza, N, Hardouin, A, Berthet, P, Muller, D, Fricker, J-P, Mortemousque, I, Pujol, P, Coupier, I, Lebrun, M, Kientz, C, Longy, M, Sevenet, N, Stoppa-Lyonnet, D, Isaacs, C, Caldes, T, de Al Hoya, M, Heikkinen, T, Aittomaki, K, Blanco, I, Lazaro, C, Barkardottir, RB, Soucy, P, Dumont, M, Simard, J, Montagna, M, Tognazzo, S, D'Andrea, E, Fox, S, Yan, M, Rebbeck, TR, Olopade, OI, Weitzel, JN, Lynch, HT, Ganz, PA, Tomlinson, GE, Wang, X, Fredericksen, Z, Pankratz, VS, Lindor, NM, Szabo, C, Offit, K, Sakr, R, Gaudet, M, Bhatia, J, Kauff, N, Singer, CF, Tea, M-K, Gschwantler-Kaulich, D, Fink-Retter, A, Mai, PL, Greene, MH, Imyanitov, E, O'Malley, FP, Ozcelik, H, Glendon, G, Toland, AE, Gerdes, A-M, Thomassen, M, Kruse, TA, Birk Jensen, U, Skytte, A-B, Caligo, MA, Soller, M, Henriksson, K, von Wachenfeldt, A, Arver, B, Stenmark-Askmalm, M, Karlsson, PW, Ding, YC, Neuhausen, SL, Beattie, M, Pharoah, PD, Moysich, KB, Nathanson, KL, Karlan, BY, Gross, J, John, EM, Daly, MB, Buys, SM, Southey, MC, Hopper, JL, Terry, MB, Chung, W, Miron, AF, Goldgar, D, Chenevix-Trench, G, Easton, DF, Andrulis, IL, Antoniou, AC, Family Registry, BC, Embrace, Collaborators, GS, Hebon, Network, OCG, Swe-Brca & Cimba 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', Breast Cancer Research (Online Edition), vol. 13, no. 6, pp. R110. https://doi.org/10.1186/bcr3052

@article{8cec1d64d1004e32910d157499e09c11,

title = "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",

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.",

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

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month = nov,

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doi = "http://dx.doi.org/10.1186/bcr3052",

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pages = "R110",

journal = "Breast Cancer Research",

issn = "1465-5411",

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T1 - 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

AU - Mulligan, Anna Marie

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 Roger

AU - McGuffog, Lesley

AU - Healey, Sue

AU - Sinilnikova, Olga M

AU - Janavicius, Ramunas

AU - Hansen, Thomas V O

AU - Nielsen, Finn C

AU - Ejlertsen, Bent

AU - Osorio, Ana

AU - Munoz-Repeto, Ivan

AU - Duran, Mercedes

AU - Godino, Javier

AU - Pertesi, Maroulio

AU - Benitez, 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 Ej

AU - Wijnen, Juul

AU - Gomez Garcia, Encarna B

AU - Nelen, Marcel R

AU - Kets, C Marleen

AU - Seynaeve, Caroline

AU - Tilanus-Linthorst, Madeleine Ma

AU - van der Luijt, Rob B

AU - van Os, Theo

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

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 - Schafer, Dieter

AU - Gevensleben, Heidrun

AU - Caux-Moncoutier, Virginie

AU - Fassy-Colcombet, Marion

AU - Cornelis, Francois

AU - Mazoyer, Sylvie

AU - Leone, Melanie

AU - Boutry-Kryza, Nadia

AU - Hardouin, Agnes

AU - Berthet, Pascaline

AU - Muller, Daniele

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 Al Hoya, Miguel

AU - Heikkinen, Tuomas

AU - Aittomaki, 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, Timothy R

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, Csila

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 - Birk Jensen, Uffe

AU - Skytte, Anne-Bine

AU - Caligo, Maria A

AU - Soller, Maria

AU - Henriksson, Karin

AU - von Wachenfeldt, Anna

AU - Arver, Brita

AU - Stenmark-Askmalm, Marie

AU - Karlsson, Per W.

AU - Ding, Yuan Chun

AU - Neuhausen, Susan L

AU - Beattie, Mary

AU - Pharoah, Paul Dp

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 Beth

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 - Family Registry, Breast Cancer

AU - Embrace, null

AU - Collaborators, Gemo Study

AU - Hebon, null

AU - Network, Ontario Cancer Genetics

AU - Swe-Brca, null

AU - Cimba, null

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.

U2 - http://dx.doi.org/10.1186/bcr3052

DO - http://dx.doi.org/10.1186/bcr3052

M3 - Journal article

SN - 1465-5411

VL - 13

SP - R110

JO - Breast Cancer Research

JF - Breast Cancer Research

IS - 6

ER -

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

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