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Assessing Associations between the AURKA-HMMR-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 and Bonifaci, Núria, et al. (2015) In PLoS ONE 10(4).
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... (More)
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 x 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. (Less)
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Public Library of Science
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  • pmid:25830658
  • wos:000352135600019
  • scopus:84927153607
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1932-6203
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10.1371/journal.pone.0120020
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English
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@article{3c1ca633-26d3-4982-9e8e-88f4dcc5c72d,
  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 x 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.},
  articleno    = {e0120020},
  author       = {Blanco, Ignacio and Kuchenbaecker, Karoline and Cuadras, Daniel and Wang, Xianshu and Barrowdale, Daniel and de Garibay, Gorka Ruiz and Librado, Pablo and Sánchez-Gracia, Alejandro and Rozas, Julio and Bonifaci, Núria and McGuffog, Lesley and Pankratz, Vernon S and Islam, Abul and Mateo, Francesca and Berenguer, Antoni and Petit, Anna and Català, Isabel and Brunet, Joan and Feliubadaló, Lidia and Tornero, Eva and Benítez, Javier and Osorio, Ana and Cajal, Teresa Ramón Y and Nevanlinna, Heli and Aittomäki, Kristiina and Arun, Banu K and Toland, Amanda E and Karlan, Beth Y and Walsh, Christine and Lester, Jenny 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 Jakubowska, Anna and Lubinski, Jan and Durda, Katarzyna and Jaworska-Bieniek, Katarzyna and Claes, Kathleen and Van Maerken, Tom and Díez, Orland and Hansen, Thomas V and Jønson, Lars and Gerdes, Anne-Marie and Ejlertsen, Bent and de la Hoya, Miguel and Caldés, Trinidad and Dunning, Alison M and Oliver, Clare and Fineberg, Elena and Cook, Margaret and Peock, Susan and McCann, Emma and Murray, Alex and Jacobs, Chris and Pichert, Gabriella and Lalloo, Fiona and Chu, Carol and Dorkins, Huw and Paterson, Joan and Ong, Kai-Ren and Teixeira, Manuel R and Hogervorst, Frans B L and van der Hout, Annemarie H and Seynaeve, Caroline and van der Luijt, Rob B and Ligtenberg, Marjolijn J L and Devilee, Peter 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 Piedmonte, Marion and Nerenstone, Stacy R and Bae-Jump, Victoria L and O'Malley, David M and Ratner, Elena S and Schmutzler, Rita K and Wappenschmidt, Barbara and Rhiem, Kerstin and Engel, Christoph and Meindl, Alfons and Ditsch, Nina and Arnold, Norbert and Plendl, Hansjoerg J and Niederacher, Dieter and Sutter, Christian and Wang-Gohrke, Shan and Steinemann, Doris and Preisler-Adams, Sabine and Kast, Karin and Varon-Mateeva, Raymonda and Gehrig, Andrea and Bojesen, Anders and Pedersen, Inge Sokilde and Sunde, Lone and Jensen, Uffe Birk and Thomassen, Mads and Kruse, Torben A and Foretova, Lenka and Peterlongo, Paolo and Bernard, Loris and Peissel, Bernard and Scuvera, Giulietta and Manoukian, Siranoush and Radice, Paolo and Ottini, Laura and Montagna, Marco and Agata, Simona and Maugard, Christine and Simard, Jacques and Soucy, Penny and Berger, Andreas and Fink-Retter, Anneliese and Singer, Christian F and Rappaport, Christine and Geschwantler-Kaulich, Daphne and Tea, Muy-Kheng and Pfeiler, Georg and John, Esther M and Miron, Alex and Neuhausen, Susan L and Terry, Mary Beth and Chung, Wendy K and Daly, Mary B and Goldgar, David E and Janavicius, Ramunas and Dorfling, Cecilia M and van Rensburg, Elisabeth J and Fostira, Florentia and Konstantopoulou, Irene and Garber, Judy and Godwin, Andrew K and Olah, Edith and Narod, Steven A and Rennert, Gad and Paluch, Shani Shimon and Laitman, Yael and Friedman, Eitan and Liljegren, Annelie and Rantala, Johanna and Stenmark Askmalm, Marie and Loman, Niklas and Imyanitov, Evgeny N and Hamann, Ute and Spurdle, Amanda B and Healey, Sue and Weitzel, Jeffrey N and Herzog, Josef and Margileth, David and Gorrini, Chiara and Esteller, Manel and Gómez, Antonio and Sayols, Sergi and Vidal, Enrique and Heyn, Holger and Stoppa-Lyonnet, Dominique and Léoné, Melanie and Barjhoux, Laure and Fassy-Colcombet, Marion and de Pauw, Antoine and Lasset, Christine and Ferrer, Sandra Fert and Castera, Laurent and Berthet, Pascaline and Cornelis, François and Bignon, Yves-Jean and Damiola, Francesca and Mazoyer, Sylvie and Sinilnikova, Olga M and Maxwell, Christopher A and Vijai, Joseph and Robson, Mark and Kauff, Noah and Corines, Marina J and Villano, Danylko and Cunningham, Julie and Lee, Adam and Lindor, Noralane and Lázaro, Conxi and Easton, Douglas F and Offit, Kenneth and Chenevix-Trench, Georgia and Couch, Fergus J and Antoniou, Antonis C and Pujana, Miguel Angel},
  issn         = {1932-6203},
  language     = {eng},
  number       = {4},
  publisher    = {Public Library of Science},
  series       = {PLoS ONE},
  title        = {Assessing Associations between the AURKA-HMMR-TPX2-TUBG1 Functional Module and Breast Cancer Risk in BRCA1/2 Mutation Carriers.},
  url          = {http://dx.doi.org/10.1371/journal.pone.0120020},
  volume       = {10},
  year         = {2015},
}