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 E. 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 Morey 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

Research output: Contribution to journalArticle

48 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 languageEnglish (US)
Article numberR110
JournalBreast Cancer Research
Volume13
Issue number6
DOIs
StatePublished - Nov 2 2011

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Alleles
Estrogens
Research Personnel
Breast Neoplasms
Mutation
Neoplasms
Single Nucleotide Polymorphism
Progesterone Receptors
Estrogen Receptors
Genotype

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

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

In: Breast Cancer Research, Vol. 13, No. 6, R110, 02.11.2011.

Research output: Contribution to journalArticle

Mulligan, AM, Couch, FJ, Barrowdale, D, Domchek, SM, Eccles, D, Nevanlinna, H, Ramus, SJ, Robson, M, Sherman, ME, 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, no. 6, R110. https://doi.org/10.1186/bcr3052
Mulligan, Anna M. ; Couch, Fergus J ; Barrowdale, Daniel ; Domchek, Susan M. ; Eccles, Diana ; Nevanlinna, Heli ; Ramus, Susan J. ; Robson, Mark ; Sherman, Mark E. ; Spurdle, Amanda B. ; Wappenschmidt, Barbara ; Lee, Andrew ; McGuffog, Lesley ; Healey, Sue ; Sinilnikova, Olga M. ; Janavicius, Ramunas ; Hansen, Thomas V. ; Nielsen, Finn C. ; Ejlertsen, Bent ; Osorio, Ana ; Muñoz-Repeto, Iván ; Durán, Mercedes ; Godino, Javier ; Pertesi, Maroulio ; Benítez, Javier ; Peterlongo, Paolo ; Manoukian, Siranoush ; Peissel, Bernard ; Zaffaroni, Daniela ; Cattaneo, Elisa ; Bonanni, Bernardo ; Viel, Alessandra ; Pasini, Barbara ; Papi, Laura ; Ottini, Laura ; Savarese, Antonella ; Bernard, Loris ; Radice, Paolo ; Hamann, Ute ; Verheus, Martijn ; Meijers-Heijboer, Hanne E J ; Wijnen, Juul ; Gómez García, Encarna B. ; Nelen, Marcel R. ; Kets, C. Marleen ; Seynaeve, Caroline ; Tilanus-Linthorst, Madeleine M A ; van der Luijt, Rob B. ; Os, Theo V. ; Rookus, Matti ; Frost, Debra ; Jones, J. Louise ; Evans, D. Gareth ; Lalloo, Fiona ; Eeles, Ros ; Izatt, Louise ; Adlard, Julian ; Davidson, Rosemarie ; Cook, Jackie ; Donaldson, Alan ; Dorkins, Huw ; Gregory, Helen ; Eason, Jacqueline ; Houghton, Catherine ; Barwell, Julian ; Side, Lucy E. ; McCann, Emma ; Murray, Alex ; Peock, Susan ; Godwin, Andrew K. ; Schmutzler, Rita K. ; Rhiem, Kerstin ; Engel, Christoph ; Meindl, Alfons ; Ruehl, Ina ; Arnold, Norbert ; Niederacher, Dieter ; Sutter, Christian ; Deissler, Helmut ; Gadzicki, Dorothea ; Kast, Karin ; Preisler-Adams, Sabine ; Varon-Mateeva, Raymonda ; Schoenbuchner, Ines ; Fiebig, Britta ; Heinritz, Wolfram ; Schäfer, Dieter ; Gevensleben, Heidrun ; Caux-Moncoutier, Virginie ; Fassy-Colcombet, Marion ; Cornelis, François ; Mazoyer, Sylvie ; Léoné, Mélanie ; Boutry-Kryza, Nadia ; Hardouin, Agnès ; Berthet, Pascaline ; Muller, Danièle ; Fricker, Jean Pierre ; Mortemousque, Isabelle ; Pujol, Pascal ; Coupier, Isabelle ; Lebrun, Marine ; Kientz, Caroline ; Longy, Michel ; Sevenet, Nicolas ; Stoppa-Lyonnet, Dominique ; Isaacs, Claudine ; Caldes, Trinidad ; de la Hoya, Miguel ; Heikkinen, Tuomas ; Aittomäki, Kristiina ; Blanco, Ignacio ; Lazaro, Conxi ; Barkardottir, Rosa B. ; Soucy, Penny ; Dumont, Martine ; Simard, Jacques ; Montagna, Marco ; Tognazzo, Silvia ; D'Andrea, Emma ; Fox, Stephen ; Yan, Max ; Rebbeck, Tim ; Olopade, Olufunmilayo I. ; Weitzel, Jeffrey N. ; Lynch, Henry T. ; Ganz, Patricia A. ; Tomlinson, Gail E. ; Wang, Xianshu ; Fredericksen, Zachary ; Pankratz, Vernon S. ; Lindor, Noralane Morey ; Szabo, Csilla ; Offit, Kenneth ; Sakr, Rita ; Gaudet, Mia ; Bhatia, Jasmine ; Kauff, Noah ; Singer, Christian F. ; Tea, Muy Kheng ; 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 ; Thomassen, Mads ; Kruse, Torben A. ; Jensen, Uffe B. ; Skytte, Anne Bine ; Caligo, Maria A. ; Soller, Maria ; Henriksson, Karin ; Wachenfeldt, von Anna ; Arver, Brita ; Stenmark-Askmalm, Marie ; Karlsson, Per ; Ding, Yuan C. ; Neuhausen, Susan L. ; Beattie, Mary ; Pharoah, Paul D P ; Moysich, Kirsten B. ; Nathanson, Katherine L. ; Karlan, Beth Y. ; Gross, Jenny ; John, Esther M. ; Daly, Mary B. ; Buys, Saundra M. ; Southey, Melissa C. ; Hopper, John L. ; Terry, Mary B. ; Chung, Wendy ; Miron, Alexander F. ; Goldgar, David ; Chenevix-Trench, Georgia ; Easton, Douglas F. ; Andrulis, Irene L. ; Antoniou, Antonis C. / 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. In: Breast Cancer Research. 2011 ; Vol. 13, No. 6.
@article{3d0b9140049b4ef99e1730dc8083c844,
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 Sherman, {Mark E.} 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{\cc}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 Morey} 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.}",
year = "2011",
month = "11",
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 E.

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 Morey

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.

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.

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U2 - 10.1186/bcr3052

DO - 10.1186/bcr3052

M3 - Article

C2 - 22053997

AN - SCOPUS:80055117035

VL - 13

JO - Breast Cancer Research

JF - Breast Cancer Research

SN - 1465-5411

IS - 6

M1 - R110

ER -