Assessing associations between the AURKAHMMR-TPX2-TUBG1 functional module and breast cancer risk in BRCA1/2 mutation carriers

Ignacio Blanco, Karoline Kuchenbaecker, Daniel Cuadras, Xianshu Wang, Daniel Barrowdale, Gorka Ruiz De Garibay, Pablo Librado, Alejandro Sánchez-Gracia, Julio Rozas, Núria Bonifaci, Lesley McGuffog, Vernon S. Pankratz, Abul Islam, Francesca Mateo, Antoni Berenguer, Anna Petit, Isabel Català, Joan Brunet, Lidia Feliubadaló, Eva TorneroJavier Benítez, Ana Osorio, Ramón Teresa, Cajal Teresa, Heli Nevanlinna, Kristiina Aittomäki, Banu K. Arun, Amanda E. Toland, Beth Y. Karlan, Christine Walsh, Jenny Lester, Mark H. Greene, Phuong L. Mai, Robert L. Nussbaum, Irene L. Andrulis, Susan M. Domchek, Katherine L. Nathanson, Timothy R. Rebbeck, Rosa B. Barkardottir, Anna Jakubowska, Jan Lubinski, Katarzyna Durda, Katarzyna Jaworska-Bieniek, Kathleen Claes, Tom Van Maerken, Orland Díez, Thomas V. Hansen, Lars Jønson, Anne Marie Gerdes, Bent Ejlertsen, Miguel De La Hoya, Trinidad Caldés, Alison M. Dunning, Clare Oliver, Elena Fineberg, Margaret Cook, Susan Peock, Emma McCann, Alex Murray, Chris Jacobs, Gabriella Pichert, Fiona Lalloo, Carol Chu, Huw Dorkins, Joan Paterson, Kai Ren Ong, Manuel R. Teixeira, T. Teixeira, Frans B L Hogervorst, Annemarie H. Van Der Hout, Caroline Seynaeve, Rob B. Van Der Luijt, Marjolijn J L Ligtenberg, Peter Devilee, Juul T. Wijnen, Matti A. Rookus, Hanne E J Meijers-Heijboer, Marinus J. Blok, Ans M W Van Den Ouweland, Cora M. Aalfs, Gustavo C. Rodriguez, Kelly Anne A Phillips, Marion Piedmonte, Stacy R. Nerenstone, Victoria L. Bae-Jump, David M. O'Malley, Elena S. Ratner, Rita K. Schmutzler, Barbara Wappenschmidt, Kerstin Rhiem, Christoph Engel, Alfons Meindl, Nina Ditsch, Norbert Arnold, Hansjoerg J. Plendl, Dieter Niederacher, Christian Sutter, Shan Wang-Gohrke, Doris Steinemann, Sabine Preisler-Adams, Karin Kast, Raymonda Varon-Mateeva, Andrea Gehrig, Anders Bojesen, Inge Sokilde Pedersen, Lone Sunde, Uffe Birk Jensen, Mads Thomassen, Torben A. Kruse, Lenka Foretova, Paolo Peterlongo, Loris Bernard, Bernard Peissel, Giulietta Scuvera, Siranoush Manoukian, Paolo Radice, Laura Ottini, Marco Montagna, Simona Agata, Christine Maugard, Jacques Simard, Penny Soucy, Andreas Berger, Anneliese Fink-Retter, Christian F. Singer, Christine Rappaport, Daphne Geschwantler-Kaulich, Muy Kheng Tea, Georg Pfeiler, Esther M. John, Alex Miron, Susan L. Neuhausen, Mary Beth Terry, Wendy K. Chung, Mary B. Daly, David E. Goldgar, Ramunas Janavicius, Cecilia M. Dorfling, Elisabeth J. Van Rensburg, Florentia Fostira, Irene Konstantopoulou, Judy Garber, Andrew K. Godwin, Edith Olah, Steven A. Narod, Gad Rennert, Shani Shimon Paluch, Yael Laitman, Eitan Friedman, Annelie Liljegren, Johanna Rantala, Marie Stenmark-Askmalm, Niklas Loman, Evgeny N. Imyanitov, Ute Hamann, Amanda B. Spurdle, Sue Healey, Jeffrey N. Weitzel, Josef Herzog, David Margileth, Chiara Gorrini, Manel Esteller, Antonio Gómez, Sergi Sayols, Enrique Vidal, Holger Heyn, Dominique Stoppa-Lyonnet, Melanie Léoné, Laure Barjhoux, Marion Fassy-Colcombet, Antoine De Pauw, Christine Lasset, Sandra Fert Ferrer, Laurent Castera, Pascaline Berthet, François Cornelis, Yves Jean Bignon, Francesca Damiola, Sylvie Mazoyer, Olga M. Sinilnikova, Christopher A. Maxwell, Joseph Vijai, Mark Robson, Noah Kauff, Marina J. Corines, Danylko Villano, Julie Cunningham, Adam Lee, Noralane Lindor, Conxi Lázaro, Douglas F. Easton, Kenneth Offit, Georgia Chenevix-Trench, Fergus J. Couch, Antonis C. Antoniou, Miguel Angel Pujana

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between the AURKA-HMMR-TPX2-TUBG1 functional module and risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Forty-one single nucleotide polymorphisms (SNPs) were genotyped in 15,252 BRCA1 and 8,211 BRCA2 mutation carriers and subsequently analyzed using a retrospective likelihood approach. The association of HMMR rs299290 with breast cancer risk in BRCA1 mutation carriers was confirmed: per-allele hazard ratio (HR) = 1.10, 95% confidence interval (CI) 1.04 - 1.15, p = 1.9 × 10-4 (false discovery rate (FDR)-adjusted p = 0.043). Variation in CSTF1, located next to AURKA, was also found to be associated with breast cancer risk in BRCA2 mutation carriers: rs2426618 per-allele HR = 1.10, 95% CI 1.03 - 1.16, p = 0.005 (FDR-adjusted p = 0.045). Assessment of pairwise interactions provided suggestions (FDR-adjusted pinteraction values > 0.05) for deviations from the multiplicative model for rs299290 and CSTF1 rs6064391, and rs299290 and TUBG1 rs11649877 in both BRCA1 and BRCA2 mutation carriers. Following these suggestions, the expression of HMMR and AURKA or TUBG1 in sporadic breast tumors was found to potentially interact, influencing patients' survival. Together, the results of this study support the hypothesis of a causative link between altered function of AURKA-HMMR-TPX2-TUBG1 and breast carcinogenesis in BRCA1/2 mutation carriers.

Original languageEnglish
Article number120020
JournalPLoS One
Volume10
Issue number4
DOIs
Publication statusPublished - Apr 1 2015

Fingerprint

Aurora Kinase A
breast neoplasms
Breast Neoplasms
mutation
Mutation
Hazards
breasts
confidence interval
Breast
Alleles
Polymorphism
Confidence Intervals
alleles
Tumors
Nucleotides
Genes
Polarization
carcinogenesis
single nucleotide polymorphism
Single Nucleotide Polymorphism

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Blanco, I., Kuchenbaecker, K., Cuadras, D., Wang, X., Barrowdale, D., De Garibay, G. R., ... Pujana, M. A. (2015). Assessing associations between the AURKAHMMR-TPX2-TUBG1 functional module and breast cancer risk in BRCA1/2 mutation carriers. PLoS One, 10(4), [120020]. https://doi.org/10.1371/journal.pone.0120020

Assessing associations between the AURKAHMMR-TPX2-TUBG1 functional module and breast cancer risk in BRCA1/2 mutation carriers. / Blanco, Ignacio; Kuchenbaecker, Karoline; Cuadras, Daniel; Wang, Xianshu; Barrowdale, Daniel; De Garibay, Gorka Ruiz; Librado, Pablo; Sánchez-Gracia, Alejandro; Rozas, Julio; Bonifaci, Núria; McGuffog, Lesley; Pankratz, Vernon S.; Islam, Abul; Mateo, Francesca; Berenguer, Antoni; Petit, Anna; Català, Isabel; Brunet, Joan; Feliubadaló, Lidia; Tornero, Eva; Benítez, Javier; Osorio, Ana; Teresa, Ramón; Teresa, Cajal; Nevanlinna, Heli; Aittomäki, Kristiina; Arun, Banu K.; Toland, Amanda E.; Karlan, Beth Y.; Walsh, Christine; Lester, Jenny; Greene, Mark H.; Mai, Phuong L.; Nussbaum, Robert L.; Andrulis, Irene L.; Domchek, Susan M.; Nathanson, Katherine L.; Rebbeck, Timothy R.; Barkardottir, Rosa B.; Jakubowska, Anna; Lubinski, Jan; Durda, Katarzyna; Jaworska-Bieniek, Katarzyna; Claes, Kathleen; Van Maerken, Tom; Díez, Orland; Hansen, Thomas V.; Jønson, Lars; Gerdes, Anne Marie; Ejlertsen, Bent; De La Hoya, Miguel; Caldés, Trinidad; Dunning, Alison M.; Oliver, Clare; Fineberg, Elena; Cook, Margaret; Peock, Susan; McCann, Emma; Murray, Alex; Jacobs, Chris; Pichert, Gabriella; Lalloo, Fiona; Chu, Carol; Dorkins, Huw; Paterson, Joan; Ong, Kai Ren; Teixeira, Manuel R.; Teixeira, T.; Hogervorst, Frans B L; Van Der Hout, Annemarie H.; Seynaeve, Caroline; Van Der Luijt, Rob B.; Ligtenberg, Marjolijn J L; Devilee, Peter; Wijnen, Juul T.; Rookus, Matti A.; Meijers-Heijboer, Hanne E J; Blok, Marinus J.; Van Den Ouweland, Ans M W; Aalfs, Cora M.; Rodriguez, Gustavo C.; Phillips, Kelly Anne A; Piedmonte, Marion; Nerenstone, Stacy R.; Bae-Jump, Victoria L.; O'Malley, David M.; Ratner, Elena S.; Schmutzler, Rita K.; Wappenschmidt, Barbara; Rhiem, Kerstin; Engel, Christoph; Meindl, Alfons; Ditsch, Nina; Arnold, Norbert; Plendl, Hansjoerg J.; Niederacher, Dieter; Sutter, Christian; Wang-Gohrke, Shan; Steinemann, Doris; Preisler-Adams, Sabine; Kast, Karin; Varon-Mateeva, Raymonda; Gehrig, Andrea; Bojesen, Anders; Pedersen, Inge Sokilde; Sunde, Lone; Jensen, Uffe Birk; Thomassen, Mads; Kruse, Torben A.; Foretova, Lenka; Peterlongo, Paolo; Bernard, Loris; Peissel, Bernard; Scuvera, Giulietta; Manoukian, Siranoush; Radice, Paolo; Ottini, Laura; Montagna, Marco; Agata, Simona; Maugard, Christine; Simard, Jacques; Soucy, Penny; Berger, Andreas; Fink-Retter, Anneliese; Singer, Christian F.; Rappaport, Christine; Geschwantler-Kaulich, Daphne; Tea, Muy Kheng; Pfeiler, Georg; John, Esther M.; Miron, Alex; Neuhausen, Susan L.; Terry, Mary Beth; Chung, Wendy K.; Daly, Mary B.; Goldgar, David E.; Janavicius, Ramunas; Dorfling, Cecilia M.; Van Rensburg, Elisabeth J.; Fostira, Florentia; Konstantopoulou, Irene; Garber, Judy; Godwin, Andrew K.; Olah, Edith; Narod, Steven A.; Rennert, Gad; Paluch, Shani Shimon; Laitman, Yael; Friedman, Eitan; Liljegren, Annelie; Rantala, Johanna; Stenmark-Askmalm, Marie; Loman, Niklas; Imyanitov, Evgeny N.; Hamann, Ute; Spurdle, Amanda B.; Healey, Sue; Weitzel, Jeffrey N.; Herzog, Josef; Margileth, David; Gorrini, Chiara; Esteller, Manel; Gómez, Antonio; Sayols, Sergi; Vidal, Enrique; Heyn, Holger; Stoppa-Lyonnet, Dominique; Léoné, Melanie; Barjhoux, Laure; Fassy-Colcombet, Marion; De Pauw, Antoine; Lasset, Christine; Ferrer, Sandra Fert; Castera, Laurent; Berthet, Pascaline; Cornelis, François; Bignon, Yves Jean; Damiola, Francesca; Mazoyer, Sylvie; Sinilnikova, Olga M.; Maxwell, Christopher A.; Vijai, Joseph; Robson, Mark; Kauff, Noah; Corines, Marina J.; Villano, Danylko; Cunningham, Julie; Lee, Adam; Lindor, Noralane; Lázaro, Conxi; Easton, Douglas F.; Offit, Kenneth; Chenevix-Trench, Georgia; Couch, Fergus J.; Antoniou, Antonis C.; Pujana, Miguel Angel.

In: PLoS One, Vol. 10, No. 4, 120020, 01.04.2015.

Research output: Contribution to journalArticle

Blanco, I, Kuchenbaecker, K, Cuadras, D, Wang, X, Barrowdale, D, De Garibay, GR, Librado, P, Sánchez-Gracia, A, Rozas, J, Bonifaci, N, McGuffog, L, Pankratz, VS, Islam, A, Mateo, F, Berenguer, A, Petit, A, Català, I, Brunet, J, Feliubadaló, L, Tornero, E, Benítez, J, Osorio, A, Teresa, R, Teresa, C, Nevanlinna, H, Aittomäki, K, Arun, BK, Toland, AE, Karlan, BY, Walsh, C, Lester, J, Greene, MH, Mai, PL, Nussbaum, RL, Andrulis, IL, Domchek, SM, Nathanson, KL, Rebbeck, TR, Barkardottir, RB, Jakubowska, A, Lubinski, J, Durda, K, Jaworska-Bieniek, K, Claes, K, Van Maerken, T, Díez, O, Hansen, TV, Jønson, L, Gerdes, AM, Ejlertsen, B, De La Hoya, M, Caldés, T, Dunning, AM, Oliver, C, Fineberg, E, Cook, M, Peock, S, McCann, E, Murray, A, Jacobs, C, Pichert, G, Lalloo, F, Chu, C, Dorkins, H, Paterson, J, Ong, KR, Teixeira, MR, Teixeira, T, Hogervorst, FBL, Van Der Hout, AH, Seynaeve, C, Van Der Luijt, RB, Ligtenberg, MJL, Devilee, P, Wijnen, JT, Rookus, MA, Meijers-Heijboer, HEJ, Blok, MJ, Van Den Ouweland, AMW, Aalfs, CM, Rodriguez, GC, Phillips, KAA, Piedmonte, M, Nerenstone, SR, Bae-Jump, VL, O'Malley, DM, Ratner, ES, Schmutzler, RK, Wappenschmidt, B, Rhiem, K, Engel, C, Meindl, A, Ditsch, N, Arnold, N, Plendl, HJ, Niederacher, D, Sutter, C, Wang-Gohrke, S, Steinemann, D, Preisler-Adams, S, Kast, K, Varon-Mateeva, R, Gehrig, A, Bojesen, A, Pedersen, IS, Sunde, L, Jensen, UB, Thomassen, M, Kruse, TA, Foretova, L, Peterlongo, P, Bernard, L, Peissel, B, Scuvera, G, Manoukian, S, Radice, P, Ottini, L, Montagna, M, Agata, S, Maugard, C, Simard, J, Soucy, P, Berger, A, Fink-Retter, A, Singer, CF, Rappaport, C, Geschwantler-Kaulich, D, Tea, MK, Pfeiler, G, John, EM, Miron, A, Neuhausen, SL, Terry, MB, Chung, WK, Daly, MB, Goldgar, DE, Janavicius, R, Dorfling, CM, Van Rensburg, EJ, Fostira, F, Konstantopoulou, I, Garber, J, Godwin, AK, Olah, E, Narod, SA, Rennert, G, Paluch, SS, Laitman, Y, Friedman, E, Liljegren, A, Rantala, J, Stenmark-Askmalm, M, Loman, N, Imyanitov, EN, Hamann, U, Spurdle, AB, Healey, S, Weitzel, JN, Herzog, J, Margileth, D, Gorrini, C, Esteller, M, Gómez, A, Sayols, S, Vidal, E, Heyn, H, Stoppa-Lyonnet, D, Léoné, M, Barjhoux, L, Fassy-Colcombet, M, De Pauw, A, Lasset, C, Ferrer, SF, Castera, L, Berthet, P, Cornelis, F, Bignon, YJ, Damiola, F, Mazoyer, S, Sinilnikova, OM, Maxwell, CA, Vijai, J, Robson, M, Kauff, N, Corines, MJ, Villano, D, Cunningham, J, Lee, A, Lindor, N, Lázaro, C, Easton, DF, Offit, K, Chenevix-Trench, G, Couch, FJ, Antoniou, AC & Pujana, MA 2015, 'Assessing associations between the AURKAHMMR-TPX2-TUBG1 functional module and breast cancer risk in BRCA1/2 mutation carriers', PLoS One, vol. 10, no. 4, 120020. https://doi.org/10.1371/journal.pone.0120020
Blanco, Ignacio ; Kuchenbaecker, Karoline ; Cuadras, Daniel ; Wang, Xianshu ; Barrowdale, Daniel ; De Garibay, Gorka Ruiz ; Librado, Pablo ; Sánchez-Gracia, Alejandro ; Rozas, Julio ; Bonifaci, Núria ; McGuffog, Lesley ; Pankratz, Vernon S. ; Islam, Abul ; Mateo, Francesca ; Berenguer, Antoni ; Petit, Anna ; Català, Isabel ; Brunet, Joan ; Feliubadaló, Lidia ; Tornero, Eva ; Benítez, Javier ; Osorio, Ana ; Teresa, Ramón ; Teresa, Cajal ; Nevanlinna, Heli ; Aittomäki, Kristiina ; Arun, Banu K. ; Toland, Amanda E. ; Karlan, Beth Y. ; Walsh, Christine ; Lester, Jenny ; Greene, Mark H. ; Mai, Phuong L. ; Nussbaum, Robert L. ; Andrulis, Irene L. ; Domchek, Susan M. ; Nathanson, Katherine L. ; Rebbeck, Timothy R. ; Barkardottir, Rosa B. ; Jakubowska, Anna ; Lubinski, Jan ; Durda, Katarzyna ; Jaworska-Bieniek, Katarzyna ; Claes, Kathleen ; Van Maerken, Tom ; Díez, Orland ; Hansen, Thomas V. ; Jønson, Lars ; Gerdes, Anne Marie ; Ejlertsen, Bent ; De La Hoya, Miguel ; Caldés, Trinidad ; Dunning, Alison M. ; Oliver, Clare ; Fineberg, Elena ; Cook, Margaret ; Peock, Susan ; McCann, Emma ; Murray, Alex ; Jacobs, Chris ; Pichert, Gabriella ; Lalloo, Fiona ; Chu, Carol ; Dorkins, Huw ; Paterson, Joan ; Ong, Kai Ren ; Teixeira, Manuel R. ; Teixeira, T. ; Hogervorst, Frans B L ; Van Der Hout, Annemarie H. ; Seynaeve, Caroline ; Van Der Luijt, Rob B. ; Ligtenberg, Marjolijn J L ; Devilee, Peter ; Wijnen, Juul T. ; Rookus, Matti A. ; Meijers-Heijboer, Hanne E J ; Blok, Marinus J. ; Van Den Ouweland, Ans M W ; Aalfs, Cora M. ; Rodriguez, Gustavo C. ; Phillips, Kelly Anne A ; Piedmonte, Marion ; Nerenstone, Stacy R. ; Bae-Jump, Victoria L. ; O'Malley, David M. ; Ratner, Elena S. ; Schmutzler, Rita K. ; Wappenschmidt, Barbara ; Rhiem, Kerstin ; Engel, Christoph ; Meindl, Alfons ; Ditsch, Nina ; Arnold, Norbert ; Plendl, Hansjoerg J. ; Niederacher, Dieter ; Sutter, Christian ; Wang-Gohrke, Shan ; Steinemann, Doris ; Preisler-Adams, Sabine ; Kast, Karin ; Varon-Mateeva, Raymonda ; Gehrig, Andrea ; Bojesen, Anders ; Pedersen, Inge Sokilde ; Sunde, Lone ; Jensen, Uffe Birk ; Thomassen, Mads ; Kruse, Torben A. ; Foretova, Lenka ; Peterlongo, Paolo ; Bernard, Loris ; Peissel, Bernard ; Scuvera, Giulietta ; Manoukian, Siranoush ; Radice, Paolo ; Ottini, Laura ; Montagna, Marco ; Agata, Simona ; Maugard, Christine ; Simard, Jacques ; Soucy, Penny ; Berger, Andreas ; Fink-Retter, Anneliese ; Singer, Christian F. ; Rappaport, Christine ; Geschwantler-Kaulich, Daphne ; Tea, Muy Kheng ; Pfeiler, Georg ; John, Esther M. ; Miron, Alex ; Neuhausen, Susan L. ; Terry, Mary Beth ; Chung, Wendy K. ; Daly, Mary B. ; Goldgar, David E. ; Janavicius, Ramunas ; Dorfling, Cecilia M. ; Van Rensburg, Elisabeth J. ; Fostira, Florentia ; Konstantopoulou, Irene ; Garber, Judy ; Godwin, Andrew K. ; Olah, Edith ; Narod, Steven A. ; Rennert, Gad ; Paluch, Shani Shimon ; Laitman, Yael ; Friedman, Eitan ; Liljegren, Annelie ; Rantala, Johanna ; Stenmark-Askmalm, Marie ; Loman, Niklas ; Imyanitov, Evgeny N. ; Hamann, Ute ; Spurdle, Amanda B. ; Healey, Sue ; Weitzel, Jeffrey N. ; Herzog, Josef ; Margileth, David ; Gorrini, Chiara ; Esteller, Manel ; Gómez, Antonio ; Sayols, Sergi ; Vidal, Enrique ; Heyn, Holger ; Stoppa-Lyonnet, Dominique ; Léoné, Melanie ; Barjhoux, Laure ; Fassy-Colcombet, Marion ; De Pauw, Antoine ; Lasset, Christine ; Ferrer, Sandra Fert ; Castera, Laurent ; Berthet, Pascaline ; Cornelis, François ; Bignon, Yves Jean ; Damiola, Francesca ; Mazoyer, Sylvie ; Sinilnikova, Olga M. ; Maxwell, Christopher A. ; Vijai, Joseph ; Robson, Mark ; Kauff, Noah ; Corines, Marina J. ; Villano, Danylko ; Cunningham, Julie ; Lee, Adam ; Lindor, Noralane ; Lázaro, Conxi ; Easton, Douglas F. ; Offit, Kenneth ; Chenevix-Trench, Georgia ; Couch, Fergus J. ; Antoniou, Antonis C. ; Pujana, Miguel Angel. / Assessing associations between the AURKAHMMR-TPX2-TUBG1 functional module and breast cancer risk in BRCA1/2 mutation carriers. In: PLoS One. 2015 ; Vol. 10, No. 4.
@article{9c0d7d10491a475a8cb2c2e02ac5680d,
title = "Assessing associations between the AURKAHMMR-TPX2-TUBG1 functional module and breast cancer risk in BRCA1/2 mutation carriers",
abstract = "While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between the AURKA-HMMR-TPX2-TUBG1 functional module and risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Forty-one single nucleotide polymorphisms (SNPs) were genotyped in 15,252 BRCA1 and 8,211 BRCA2 mutation carriers and subsequently analyzed using a retrospective likelihood approach. The association of HMMR rs299290 with breast cancer risk in BRCA1 mutation carriers was confirmed: per-allele hazard ratio (HR) = 1.10, 95{\%} confidence interval (CI) 1.04 - 1.15, p = 1.9 × 10-4 (false discovery rate (FDR)-adjusted p = 0.043). Variation in CSTF1, located next to AURKA, was also found to be associated with breast cancer risk in BRCA2 mutation carriers: rs2426618 per-allele HR = 1.10, 95{\%} CI 1.03 - 1.16, p = 0.005 (FDR-adjusted p = 0.045). Assessment of pairwise interactions provided suggestions (FDR-adjusted pinteraction values > 0.05) for deviations from the multiplicative model for rs299290 and CSTF1 rs6064391, and rs299290 and TUBG1 rs11649877 in both BRCA1 and BRCA2 mutation carriers. Following these suggestions, the expression of HMMR and AURKA or TUBG1 in sporadic breast tumors was found to potentially interact, influencing patients' survival. Together, the results of this study support the hypothesis of a causative link between altered function of AURKA-HMMR-TPX2-TUBG1 and breast carcinogenesis in BRCA1/2 mutation carriers.",
author = "Ignacio Blanco and Karoline Kuchenbaecker and Daniel Cuadras and Xianshu Wang and Daniel Barrowdale and {De Garibay}, {Gorka Ruiz} and Pablo Librado and Alejandro S{\'a}nchez-Gracia and Julio Rozas and N{\'u}ria Bonifaci and Lesley McGuffog and Pankratz, {Vernon S.} and Abul Islam and Francesca Mateo and Antoni Berenguer and Anna Petit and Isabel Catal{\`a} and Joan Brunet and Lidia Feliubadal{\'o} and Eva Tornero and Javier Ben{\'i}tez and Ana Osorio and Ram{\'o}n Teresa and Cajal Teresa and Heli Nevanlinna and Kristiina Aittom{\"a}ki and Arun, {Banu K.} and Toland, {Amanda E.} and Karlan, {Beth Y.} and Christine Walsh and Jenny Lester and Greene, {Mark H.} and Mai, {Phuong L.} and Nussbaum, {Robert L.} and Andrulis, {Irene L.} and Domchek, {Susan M.} and Nathanson, {Katherine L.} and Rebbeck, {Timothy R.} and Barkardottir, {Rosa B.} and Anna Jakubowska and Jan Lubinski and Katarzyna Durda and Katarzyna Jaworska-Bieniek and Kathleen Claes and {Van Maerken}, Tom and Orland D{\'i}ez and Hansen, {Thomas V.} and Lars J{\o}nson and Gerdes, {Anne Marie} and Bent Ejlertsen and {De La Hoya}, Miguel and Trinidad Cald{\'e}s and Dunning, {Alison M.} and Clare Oliver and Elena Fineberg and Margaret Cook and Susan Peock and Emma McCann and Alex Murray and Chris Jacobs and Gabriella Pichert and Fiona Lalloo and Carol Chu and Huw Dorkins and Joan Paterson and Ong, {Kai Ren} and Teixeira, {Manuel R.} and T. Teixeira and Hogervorst, {Frans B L} and {Van Der Hout}, {Annemarie H.} and Caroline Seynaeve and {Van Der Luijt}, {Rob B.} and Ligtenberg, {Marjolijn J L} and Peter Devilee and Wijnen, {Juul T.} and Rookus, {Matti A.} and Meijers-Heijboer, {Hanne E J} and Blok, {Marinus J.} and {Van Den Ouweland}, {Ans M W} and Aalfs, {Cora M.} and Rodriguez, {Gustavo C.} and Phillips, {Kelly Anne A} and Marion Piedmonte and Nerenstone, {Stacy R.} and Bae-Jump, {Victoria L.} and O'Malley, {David M.} and Ratner, {Elena S.} and Schmutzler, {Rita K.} and Barbara Wappenschmidt and Kerstin Rhiem and Christoph Engel and Alfons Meindl and Nina Ditsch and Norbert Arnold and Plendl, {Hansjoerg J.} and Dieter Niederacher and Christian Sutter and Shan Wang-Gohrke and Doris Steinemann and Sabine Preisler-Adams and Karin Kast and Raymonda Varon-Mateeva and Andrea Gehrig and Anders Bojesen and Pedersen, {Inge Sokilde} and Lone Sunde and Jensen, {Uffe Birk} and Mads Thomassen and Kruse, {Torben A.} and Lenka Foretova and Paolo Peterlongo and Loris Bernard and Bernard Peissel and Giulietta Scuvera and Siranoush Manoukian and Paolo Radice and Laura Ottini and Marco Montagna and Simona Agata and Christine Maugard and Jacques Simard and Penny Soucy and Andreas Berger and Anneliese Fink-Retter and Singer, {Christian F.} and Christine Rappaport and Daphne Geschwantler-Kaulich and Tea, {Muy Kheng} and Georg Pfeiler and John, {Esther M.} and Alex Miron and Neuhausen, {Susan L.} and Terry, {Mary Beth} and Chung, {Wendy K.} and Daly, {Mary B.} and Goldgar, {David E.} and Ramunas Janavicius and Dorfling, {Cecilia M.} and {Van Rensburg}, {Elisabeth J.} and Florentia Fostira and Irene Konstantopoulou and Judy Garber and Godwin, {Andrew K.} and Edith Olah and Narod, {Steven A.} and Gad Rennert and Paluch, {Shani Shimon} and Yael Laitman and Eitan Friedman and Annelie Liljegren and Johanna Rantala and Marie Stenmark-Askmalm and Niklas Loman and Imyanitov, {Evgeny N.} and Ute Hamann and Spurdle, {Amanda B.} and Sue Healey and Weitzel, {Jeffrey N.} and Josef Herzog and David Margileth and Chiara Gorrini and Manel Esteller and Antonio G{\'o}mez and Sergi Sayols and Enrique Vidal and Holger Heyn and Dominique Stoppa-Lyonnet and Melanie L{\'e}on{\'e} and Laure Barjhoux and Marion Fassy-Colcombet and {De Pauw}, Antoine and Christine Lasset and Ferrer, {Sandra Fert} and Laurent Castera and Pascaline Berthet and Fran{\cc}ois Cornelis and Bignon, {Yves Jean} and Francesca Damiola and Sylvie Mazoyer and Sinilnikova, {Olga M.} and Maxwell, {Christopher A.} and Joseph Vijai and Mark Robson and Noah Kauff and Corines, {Marina J.} and Danylko Villano and Julie Cunningham and Adam Lee and Noralane Lindor and Conxi L{\'a}zaro and Easton, {Douglas F.} and Kenneth Offit and Georgia Chenevix-Trench and Couch, {Fergus J.} and Antoniou, {Antonis C.} and Pujana, {Miguel Angel}",
year = "2015",
month = "4",
day = "1",
doi = "10.1371/journal.pone.0120020",
language = "English",
volume = "10",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "4",

}

TY - JOUR

T1 - Assessing associations between the AURKAHMMR-TPX2-TUBG1 functional module and breast cancer risk in BRCA1/2 mutation carriers

AU - Blanco, Ignacio

AU - Kuchenbaecker, Karoline

AU - Cuadras, Daniel

AU - Wang, Xianshu

AU - Barrowdale, Daniel

AU - De Garibay, Gorka Ruiz

AU - Librado, Pablo

AU - Sánchez-Gracia, Alejandro

AU - Rozas, Julio

AU - Bonifaci, Núria

AU - McGuffog, Lesley

AU - Pankratz, Vernon S.

AU - Islam, Abul

AU - Mateo, Francesca

AU - Berenguer, Antoni

AU - Petit, Anna

AU - Català, Isabel

AU - Brunet, Joan

AU - Feliubadaló, Lidia

AU - Tornero, Eva

AU - Benítez, Javier

AU - Osorio, Ana

AU - Teresa, Ramón

AU - Teresa, Cajal

AU - Nevanlinna, Heli

AU - Aittomäki, Kristiina

AU - Arun, Banu K.

AU - Toland, Amanda E.

AU - Karlan, Beth Y.

AU - Walsh, Christine

AU - Lester, Jenny

AU - Greene, Mark H.

AU - Mai, Phuong L.

AU - Nussbaum, Robert L.

AU - Andrulis, Irene L.

AU - Domchek, Susan M.

AU - Nathanson, Katherine L.

AU - Rebbeck, Timothy R.

AU - Barkardottir, Rosa B.

AU - Jakubowska, Anna

AU - Lubinski, Jan

AU - Durda, Katarzyna

AU - Jaworska-Bieniek, Katarzyna

AU - Claes, Kathleen

AU - Van Maerken, Tom

AU - Díez, Orland

AU - Hansen, Thomas V.

AU - Jønson, Lars

AU - Gerdes, Anne Marie

AU - Ejlertsen, Bent

AU - De La Hoya, Miguel

AU - Caldés, Trinidad

AU - Dunning, Alison M.

AU - Oliver, Clare

AU - Fineberg, Elena

AU - Cook, Margaret

AU - Peock, Susan

AU - McCann, Emma

AU - Murray, Alex

AU - Jacobs, Chris

AU - Pichert, Gabriella

AU - Lalloo, Fiona

AU - Chu, Carol

AU - Dorkins, Huw

AU - Paterson, Joan

AU - Ong, Kai Ren

AU - Teixeira, Manuel R.

AU - Teixeira, T.

AU - Hogervorst, Frans B L

AU - Van Der Hout, Annemarie H.

AU - Seynaeve, Caroline

AU - Van Der Luijt, Rob B.

AU - Ligtenberg, Marjolijn J L

AU - Devilee, Peter

AU - Wijnen, Juul T.

AU - Rookus, Matti A.

AU - Meijers-Heijboer, Hanne E J

AU - Blok, Marinus J.

AU - Van Den Ouweland, Ans M W

AU - Aalfs, Cora M.

AU - Rodriguez, Gustavo C.

AU - Phillips, Kelly Anne A

AU - Piedmonte, Marion

AU - Nerenstone, Stacy R.

AU - Bae-Jump, Victoria L.

AU - O'Malley, David M.

AU - Ratner, Elena S.

AU - Schmutzler, Rita K.

AU - Wappenschmidt, Barbara

AU - Rhiem, Kerstin

AU - Engel, Christoph

AU - Meindl, Alfons

AU - Ditsch, Nina

AU - Arnold, Norbert

AU - Plendl, Hansjoerg J.

AU - Niederacher, Dieter

AU - Sutter, Christian

AU - Wang-Gohrke, Shan

AU - Steinemann, Doris

AU - Preisler-Adams, Sabine

AU - Kast, Karin

AU - Varon-Mateeva, Raymonda

AU - Gehrig, Andrea

AU - Bojesen, Anders

AU - Pedersen, Inge Sokilde

AU - Sunde, Lone

AU - Jensen, Uffe Birk

AU - Thomassen, Mads

AU - Kruse, Torben A.

AU - Foretova, Lenka

AU - Peterlongo, Paolo

AU - Bernard, Loris

AU - Peissel, Bernard

AU - Scuvera, Giulietta

AU - Manoukian, Siranoush

AU - Radice, Paolo

AU - Ottini, Laura

AU - Montagna, Marco

AU - Agata, Simona

AU - Maugard, Christine

AU - Simard, Jacques

AU - Soucy, Penny

AU - Berger, Andreas

AU - Fink-Retter, Anneliese

AU - Singer, Christian F.

AU - Rappaport, Christine

AU - Geschwantler-Kaulich, Daphne

AU - Tea, Muy Kheng

AU - Pfeiler, Georg

AU - John, Esther M.

AU - Miron, Alex

AU - Neuhausen, Susan L.

AU - Terry, Mary Beth

AU - Chung, Wendy K.

AU - Daly, Mary B.

AU - Goldgar, David E.

AU - Janavicius, Ramunas

AU - Dorfling, Cecilia M.

AU - Van Rensburg, Elisabeth J.

AU - Fostira, Florentia

AU - Konstantopoulou, Irene

AU - Garber, Judy

AU - Godwin, Andrew K.

AU - Olah, Edith

AU - Narod, Steven A.

AU - Rennert, Gad

AU - Paluch, Shani Shimon

AU - Laitman, Yael

AU - Friedman, Eitan

AU - Liljegren, Annelie

AU - Rantala, Johanna

AU - Stenmark-Askmalm, Marie

AU - Loman, Niklas

AU - Imyanitov, Evgeny N.

AU - Hamann, Ute

AU - Spurdle, Amanda B.

AU - Healey, Sue

AU - Weitzel, Jeffrey N.

AU - Herzog, Josef

AU - Margileth, David

AU - Gorrini, Chiara

AU - Esteller, Manel

AU - Gómez, Antonio

AU - Sayols, Sergi

AU - Vidal, Enrique

AU - Heyn, Holger

AU - Stoppa-Lyonnet, Dominique

AU - Léoné, Melanie

AU - Barjhoux, Laure

AU - Fassy-Colcombet, Marion

AU - De Pauw, Antoine

AU - Lasset, Christine

AU - Ferrer, Sandra Fert

AU - Castera, Laurent

AU - Berthet, Pascaline

AU - Cornelis, François

AU - Bignon, Yves Jean

AU - Damiola, Francesca

AU - Mazoyer, Sylvie

AU - Sinilnikova, Olga M.

AU - Maxwell, Christopher A.

AU - Vijai, Joseph

AU - Robson, Mark

AU - Kauff, Noah

AU - Corines, Marina J.

AU - Villano, Danylko

AU - Cunningham, Julie

AU - Lee, Adam

AU - Lindor, Noralane

AU - Lázaro, Conxi

AU - Easton, Douglas F.

AU - Offit, Kenneth

AU - Chenevix-Trench, Georgia

AU - Couch, Fergus J.

AU - Antoniou, Antonis C.

AU - Pujana, Miguel Angel

PY - 2015/4/1

Y1 - 2015/4/1

N2 - While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between the AURKA-HMMR-TPX2-TUBG1 functional module and risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Forty-one single nucleotide polymorphisms (SNPs) were genotyped in 15,252 BRCA1 and 8,211 BRCA2 mutation carriers and subsequently analyzed using a retrospective likelihood approach. The association of HMMR rs299290 with breast cancer risk in BRCA1 mutation carriers was confirmed: per-allele hazard ratio (HR) = 1.10, 95% confidence interval (CI) 1.04 - 1.15, p = 1.9 × 10-4 (false discovery rate (FDR)-adjusted p = 0.043). Variation in CSTF1, located next to AURKA, was also found to be associated with breast cancer risk in BRCA2 mutation carriers: rs2426618 per-allele HR = 1.10, 95% CI 1.03 - 1.16, p = 0.005 (FDR-adjusted p = 0.045). Assessment of pairwise interactions provided suggestions (FDR-adjusted pinteraction values > 0.05) for deviations from the multiplicative model for rs299290 and CSTF1 rs6064391, and rs299290 and TUBG1 rs11649877 in both BRCA1 and BRCA2 mutation carriers. Following these suggestions, the expression of HMMR and AURKA or TUBG1 in sporadic breast tumors was found to potentially interact, influencing patients' survival. Together, the results of this study support the hypothesis of a causative link between altered function of AURKA-HMMR-TPX2-TUBG1 and breast carcinogenesis in BRCA1/2 mutation carriers.

AB - While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between the AURKA-HMMR-TPX2-TUBG1 functional module and risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Forty-one single nucleotide polymorphisms (SNPs) were genotyped in 15,252 BRCA1 and 8,211 BRCA2 mutation carriers and subsequently analyzed using a retrospective likelihood approach. The association of HMMR rs299290 with breast cancer risk in BRCA1 mutation carriers was confirmed: per-allele hazard ratio (HR) = 1.10, 95% confidence interval (CI) 1.04 - 1.15, p = 1.9 × 10-4 (false discovery rate (FDR)-adjusted p = 0.043). Variation in CSTF1, located next to AURKA, was also found to be associated with breast cancer risk in BRCA2 mutation carriers: rs2426618 per-allele HR = 1.10, 95% CI 1.03 - 1.16, p = 0.005 (FDR-adjusted p = 0.045). Assessment of pairwise interactions provided suggestions (FDR-adjusted pinteraction values > 0.05) for deviations from the multiplicative model for rs299290 and CSTF1 rs6064391, and rs299290 and TUBG1 rs11649877 in both BRCA1 and BRCA2 mutation carriers. Following these suggestions, the expression of HMMR and AURKA or TUBG1 in sporadic breast tumors was found to potentially interact, influencing patients' survival. Together, the results of this study support the hypothesis of a causative link between altered function of AURKA-HMMR-TPX2-TUBG1 and breast carcinogenesis in BRCA1/2 mutation carriers.

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U2 - 10.1371/journal.pone.0120020

DO - 10.1371/journal.pone.0120020

M3 - Article

AN - SCOPUS:84927153607

VL - 10

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 4

M1 - 120020

ER -