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

Anna M. 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 Lee; Lesley McGuffog; Sue Healey; Olga M. Sinilnikova; Ramunas Janavicius; Thomas V. Hansen; Finn C. Nielsen; Bent Ejlertsen; Ana Osorio; Iván Muñoz-Repeto; Mercedes Durán; Javier Godino; Maroulio Pertesi; Javier Benítez; 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 E.J. Meijers-Heijboer; Juul Wijnen; Encarna B. Gómez García; Marcel R. Nelen; C. Marleen Kets; Caroline Seynaeve; Madeleine M.A. Tilanus-Linthorst; Rob B. van der Luijt; Theo V. 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 K. 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 Schäfer; Heidrun Gevensleben; Virginie Caux-Moncoutier; Marion Fassy-Colcombet; François Cornelis; Sylvie Mazoyer; Mélanie Léoné; Nadia Boutry-Kryza; Agnès Hardouin; Pascaline Berthet; Danièle 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 la Hoya; Tuomas Heikkinen; Kristiina Aittomäki; Ignacio Blanco; Conxi Lazaro; Rosa B. Barkardottir; Penny Soucy; Martine Dumont; Jacques Simard; Marco Montagna; Silvia Tognazzo; Emma D'Andrea; Stephen Fox; Max Yan; Tim 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; Csilla 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 B. Jensen; Anne Bine Skytte; Maria A. Caligo; Maria Soller; Karin Henriksson; von Anna Wachenfeldt; Brita Arver; Marie Stenmark-Askmalm; Per Karlsson; Yuan C. Ding; Susan L. Neuhausen; Mary Beattie; Paul D.P. 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 B. Terry; Wendy Chung; Alexander F. Miron; David Goldgar; Georgia Chenevix-Trench; Douglas F. Easton; Irene L. Andrulis; Antonis C. Antoniou

doi:10.1186/bcr3052

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

Anna M. 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 Lee, Lesley McGuffog, Sue Healey, Olga M. Sinilnikova, Ramunas Janavicius, Thomas V. Hansen, Finn C. Nielsen, Bent Ejlertsen, Ana OsorioIván Muñoz-Repeto, Mercedes Durán, Javier Godino, Maroulio Pertesi, Javier Benítez, 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 E.J. Meijers-Heijboer, Juul Wijnen, Encarna B. Gómez García, Marcel R. Nelen, C. Marleen Kets, Caroline Seynaeve, Madeleine M.A. Tilanus-Linthorst, Rob B. van der Luijt, Theo V. 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 K. 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 Schäfer, Heidrun Gevensleben, Virginie Caux-Moncoutier, Marion Fassy-Colcombet, François Cornelis, Sylvie Mazoyer, Mélanie Léoné, Nadia Boutry-Kryza, Agnès Hardouin, Pascaline Berthet, Danièle 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 la Hoya, Tuomas Heikkinen, Kristiina Aittomäki, Ignacio Blanco, Conxi Lazaro, Rosa B. Barkardottir, Penny Soucy, Martine Dumont, Jacques Simard, Marco Montagna, Silvia Tognazzo, Emma D'Andrea, Stephen Fox, Max Yan, Tim 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, Csilla 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 B. Jensen, Anne Bine Skytte, Maria A. Caligo, Maria Soller, Karin Henriksson, von Anna Wachenfeldt, Brita Arver, Marie Stenmark-Askmalm, Per Karlsson, Yuan C. Ding, Susan L. Neuhausen, Mary Beattie, Paul D.P. 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 B. Terry, Wendy Chung, Alexander F. Miron, David Goldgar, Georgia Chenevix-Trench, Douglas F. Easton, Irene L. Andrulis, Antonis C. Antoniou

Department of Pediatrics

Producción científica: Article › revisión exhaustiva

63 Citas (Scopus)

Resumen

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.

Idioma original	English (US)
Número de artículo	R110
Publicación	Breast Cancer Research
Volumen	13
N.º	6
DOI	https://doi.org/10.1186/bcr3052
Estado	Published - nov 2 2011

ASJC Scopus subject areas

Oncology
Cancer Research

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10.1186/bcr3052

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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., McGuffog, L., Healey, S., Sinilnikova, O. M., Janavicius, R., Hansen, T. V., Nielsen, F. C., Ejlertsen, B., ... Antoniou, A. C. (2011). 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. Breast Cancer Research, 13(6), Artículo R110. https://doi.org/10.1186/bcr3052

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 M.; Couch, Fergus J.; Barrowdale, Daniel et al.
En: Breast Cancer Research, Vol. 13, N.º 6, R110, 02.11.2011.

Producción científica: Article › revisión exhaustiva

Mulligan, AM, Couch, FJ, Barrowdale, D, Domchek, SM, Eccles, D, Nevanlinna, H, Ramus, SJ, Robson, M, Sherman, M, Spurdle, AB, Wappenschmidt, B, Lee, A, McGuffog, L, Healey, S, Sinilnikova, OM, Janavicius, R, Hansen, TV, Nielsen, FC, Ejlertsen, B, Osorio, A, Muñoz-Repeto, I, Durán, M, Godino, J, Pertesi, M, Benítez, 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, HEJ, Wijnen, J, Gómez García, EB, Nelen, MR, Kets, CM, Seynaeve, C, Tilanus-Linthorst, MMA, van der Luijt, RB, Os, TV, 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, AK, 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, Schäfer, D, Gevensleben, H, Caux-Moncoutier, V, Fassy-Colcombet, M, Cornelis, F, Mazoyer, S, Léoné, M, Boutry-Kryza, N, Hardouin, A, Berthet, P, Muller, D, Fricker, JP, Mortemousque, I, Pujol, P, Coupier, I, Lebrun, M, Kientz, C, Longy, M, Sevenet, N, Stoppa-Lyonnet, D, Isaacs, C, Caldes, T, de la Hoya, M, Heikkinen, T, Aittomäki, 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, T, 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, MK, gschwantler-kaulich, D, Fink-Retter, A, Mai, PL, Greene, MH, Imyanitov, E, O'Malley, FP, Ozcelik, H, Glendon, G, Toland, AE, Gerdes, AM, Thomassen, M, Kruse, TA, Jensen, UB, Skytte, AB, Caligo, MA, Soller, M, Henriksson, K, Wachenfeldt, VA, Arver, B, Stenmark-Askmalm, M, Karlsson, P, Ding, YC, Neuhausen, SL, Beattie, M, Pharoah, PDP, 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 2011, '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', Breast Cancer Research, vol. 13, n.º 6, R110. https://doi.org/10.1186/bcr3052

@article{8f072caaa6784b13b3f5f3b8beda0797,

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",

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 M.} 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 Andrew Lee and Lesley McGuffog and Sue Healey and Sinilnikova, {Olga M.} and Ramunas Janavicius and Hansen, {Thomas V.} and Nielsen, {Finn C.} and Bent Ejlertsen and Ana Osorio and Iv{\'a}n Mu{\~n}oz-Repeto and Mercedes Dur{\'a}n and Javier Godino and Maroulio Pertesi and Javier Ben{\'i}tez 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 E.J.} and Juul Wijnen and {G{\'o}mez Garc{\'i}a}, {Encarna B.} and Nelen, {Marcel R.} and Kets, {C. Marleen} and Caroline Seynaeve and Tilanus-Linthorst, {Madeleine M.A.} and {van der Luijt}, {Rob B.} and Os, {Theo V.} 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 Godwin, {Andrew K.} 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 Sch{\"a}fer and Heidrun Gevensleben and Virginie Caux-Moncoutier and Marion Fassy-Colcombet and Fran{\c c}ois Cornelis and Sylvie Mazoyer and M{\'e}lanie L{\'e}on{\'e} and Nadia Boutry-Kryza and Agn{\`e}s Hardouin and Pascaline Berthet and Dani{\`e}le Muller and Fricker, {Jean Pierre} 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 la Hoya}, Miguel and Tuomas Heikkinen and Kristiina Aittom{\"a}ki 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 Tim Rebbeck 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 Csilla Szabo and Kenneth Offit and Rita Sakr and Mia Gaudet and Jasmine Bhatia and Noah Kauff and Singer, {Christian F.} and Tea, {Muy Kheng} 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 Gerdes, {Anne Marie} and Mads Thomassen and Kruse, {Torben A.} and Jensen, {Uffe B.} and Skytte, {Anne Bine} and Caligo, {Maria A.} and Maria Soller and Karin Henriksson and Wachenfeldt, {von Anna} and Brita Arver and Marie Stenmark-Askmalm and Per Karlsson and Ding, {Yuan C.} and Neuhausen, {Susan L.} and Mary Beattie and Pharoah, {Paul D.P.} 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 B.} 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.}",

note = "Funding Information: ILUH The ILUH group was supported by the Icelandic Association “Walking for Breast Cancer Research” and by the Landspitali University Hospital Research Fund. Istituto Oncologico Veneto Hereditary Breast and Ovarian Cancer Study (IOVHBOCS) This study was supported by “Ministero della Salute” ({"}Progetto Tumouri Femminili and grant numbers RFPS 2006-5-341353, ACC2/R6.9”) Kathleen Cuningham Consortium for Research into Familial Breast Cancer (kConFab) We wish to thank Heather Thorne, Eveline Niedermayr, all the kConFab research nurses and staff, the heads and staff of the Family Cancer Clinics, and the Clinical Follow Up Study (funded 2001-2009 by NHMRC and currently by the National Breast Cancer Foundation and Cancer Australia #628333) for their contributions to this resource, and the many families who contribute to kConFab. kConFab is supported by grants from the National Breast Cancer Foundation, the National Health and Medical Research Council (NHMRC) and by the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia. ABS and GCT are NHMRC Fellows. Mayo Clinic Study The MAYO study was supported by NIH grants CA116167, CA128978, a Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), and awards from the Komen Foundation for the Cure and the Breast Cancer Research Foundation. Memorial Sloan-Kettering Cancer Center (MSKCC) The study is supported by grant from the Breast Cancer Research Foundation, Starr Cancer Consortium, Norman and Carol Stone Genetic Research Fund, The Robert and Kate Niehaus Clinical Genetics Initiative at MSKCC National Cancer Institute study (NCI) The research of Drs. PL Mai and MH Greene was supported by the Intramural Research Program of the US National Cancer Institute, and by support services contracts NO2-CP-11019-50 and N02-CP-65504 with Westat, Inc., Rockville, MD. N.N. Petrov Institute of Oncology This work has been supported by the Russian Federation for Basic Research (grants 10-04-92601, 10-04-92110, 11-04-00227), the Federal Agency for Science and Innovations (contract 02.740.11.0780), the Commission of the European Communities (grant PITN-GA-2009-238132) and through a Royal Society International Joint grant (JP090615). Ontario Cancer Genetics Network (OCGN) We wish to thank Mona Gill, Lucine Collins, Nalan Gokgoz, Teresa Selander, Nayana Weerasooriya and members of the Ontario Cancer Genetics Network for their contributions to the study. The Ohio State University Comprehensive Cancer Center (OSU-CCG) This work was supported by the Ohio State University Comprehensive Cancer Center. We thank Kevin Sweet and Leigha Senter for accrual of study participants and data management. The Human Genetics Sample bank prepared DNA samples and the OSU Nucleic Acids Shared Resource assisted with genotyping. Swedish BRCA1 and BRCA2 study (SWE-BRCA) SWE-BRCA collaborators: Margareta Nordling, Annika Bergman and Zakaria Einbeigi, Gothenburg, Sahlgrenska University Hospital; Sigrun Liedgren, Link{\"o}ping University Hospital; {\AA}ke Borg, Niklas Loman, H{\aa}kan Olsson, Ulf Kristoffersson, Helena Jernstr{\"o}m, Katja Harbst, Lund University Hospital; Annika Lindblom, Annelie Liljegren, Gisela Barbany-Bustinza and Johanna Rantala, Stockholm, Karolinska University Hospital; Beatrice Melin, Henrik Gr{\"o}nberg, Eva-Lena Stattin and Monica Emanuelsson, Ume{\aa} University Hospital; Hans Ehrencrona, Richard Rosenquist and Niklas Dahl, Uppsala University Hospital. University California San Francisco (UCSF) The study received funding from the NIH, NCI Bay Area Breast Cancer SPORE (P50 CA 058207) and the Avon Foundation. We acknowledge support from the UCSF Helen Diller Family Comprehensive Cancer Center UK and Gilda Radner Familial Ovarian Cancer Registries (UKGRFOCR) UKFOCR was supported by a project grant from CRUK to Paul Pharoah. We thank Simon Gayther, Carole Pye, Patricia Harrington and Eva Wozniak for their contributions towards the UKFOCR. We{\textquoteright}d like to acknowledge the Roswell Park Alliance Foundation for their continued support of the Gilda Radner Ovarian Family Cancer Registry. GRFOCR would like to acknowledge Lara Sucheston (Department of Cancer Prevention and Control) and Kunle Odunsi (Departments Gynecologic Oncology and Immunology). University of Pennsylvania (UPENN) Work is supported by grants from the Breast Cancer Research Foundation (to KLN), MacDonald Family Foundation (SMD) and Komen Foundation (SMD)",

year = "2011",

month = nov,

day = "2",

doi = "10.1186/bcr3052",

language = "English (US)",

volume = "13",

journal = "Breast Cancer Research",

issn = "1465-5411",

publisher = "BioMed Central",

number = "6",

}

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.

N1 - Funding Information: ILUH The ILUH group was supported by the Icelandic Association “Walking for Breast Cancer Research” and by the Landspitali University Hospital Research Fund. Istituto Oncologico Veneto Hereditary Breast and Ovarian Cancer Study (IOVHBOCS) This study was supported by “Ministero della Salute” ("Progetto Tumouri Femminili and grant numbers RFPS 2006-5-341353, ACC2/R6.9”) Kathleen Cuningham Consortium for Research into Familial Breast Cancer (kConFab) We wish to thank Heather Thorne, Eveline Niedermayr, all the kConFab research nurses and staff, the heads and staff of the Family Cancer Clinics, and the Clinical Follow Up Study (funded 2001-2009 by NHMRC and currently by the National Breast Cancer Foundation and Cancer Australia #628333) for their contributions to this resource, and the many families who contribute to kConFab. kConFab is supported by grants from the National Breast Cancer Foundation, the National Health and Medical Research Council (NHMRC) and by the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia. ABS and GCT are NHMRC Fellows. Mayo Clinic Study The MAYO study was supported by NIH grants CA116167, CA128978, a Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), and awards from the Komen Foundation for the Cure and the Breast Cancer Research Foundation. Memorial Sloan-Kettering Cancer Center (MSKCC) The study is supported by grant from the Breast Cancer Research Foundation, Starr Cancer Consortium, Norman and Carol Stone Genetic Research Fund, The Robert and Kate Niehaus Clinical Genetics Initiative at MSKCC National Cancer Institute study (NCI) The research of Drs. PL Mai and MH Greene was supported by the Intramural Research Program of the US National Cancer Institute, and by support services contracts NO2-CP-11019-50 and N02-CP-65504 with Westat, Inc., Rockville, MD. N.N. Petrov Institute of Oncology This work has been supported by the Russian Federation for Basic Research (grants 10-04-92601, 10-04-92110, 11-04-00227), the Federal Agency for Science and Innovations (contract 02.740.11.0780), the Commission of the European Communities (grant PITN-GA-2009-238132) and through a Royal Society International Joint grant (JP090615). Ontario Cancer Genetics Network (OCGN) We wish to thank Mona Gill, Lucine Collins, Nalan Gokgoz, Teresa Selander, Nayana Weerasooriya and members of the Ontario Cancer Genetics Network for their contributions to the study. The Ohio State University Comprehensive Cancer Center (OSU-CCG) This work was supported by the Ohio State University Comprehensive Cancer Center. We thank Kevin Sweet and Leigha Senter for accrual of study participants and data management. The Human Genetics Sample bank prepared DNA samples and the OSU Nucleic Acids Shared Resource assisted with genotyping. Swedish BRCA1 and BRCA2 study (SWE-BRCA) SWE-BRCA collaborators: Margareta Nordling, Annika Bergman and Zakaria Einbeigi, Gothenburg, Sahlgrenska University Hospital; Sigrun Liedgren, Linköping University Hospital; Åke Borg, Niklas Loman, Håkan Olsson, Ulf Kristoffersson, Helena Jernström, Katja Harbst, Lund University Hospital; Annika Lindblom, Annelie Liljegren, Gisela Barbany-Bustinza and Johanna Rantala, Stockholm, Karolinska University Hospital; Beatrice Melin, Henrik Grönberg, Eva-Lena Stattin and Monica Emanuelsson, Umeå University Hospital; Hans Ehrencrona, Richard Rosenquist and Niklas Dahl, Uppsala University Hospital. University California San Francisco (UCSF) The study received funding from the NIH, NCI Bay Area Breast Cancer SPORE (P50 CA 058207) and the Avon Foundation. We acknowledge support from the UCSF Helen Diller Family Comprehensive Cancer Center UK and Gilda Radner Familial Ovarian Cancer Registries (UKGRFOCR) UKFOCR was supported by a project grant from CRUK to Paul Pharoah. We thank Simon Gayther, Carole Pye, Patricia Harrington and Eva Wozniak for their contributions towards the UKFOCR. We’d like to acknowledge the Roswell Park Alliance Foundation for their continued support of the Gilda Radner Ovarian Family Cancer Registry. GRFOCR would like to acknowledge Lara Sucheston (Department of Cancer Prevention and Control) and Kunle Odunsi (Departments Gynecologic Oncology and Immunology). University of Pennsylvania (UPENN) Work is supported by grants from the Breast Cancer Research Foundation (to KLN), MacDonald Family Foundation (SMD) and Komen Foundation (SMD)

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

UR - http://www.scopus.com/inward/citedby.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 -

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

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