Please use this identifier to cite or link to this item: https://hdl.handle.net/20.500.12530/40460
Title: Assessing associations between the AURKA-HMMR-TPX2-TUBG1 functional module and breast cancer risk in BRCA1/2 mutation carriers.
Authors: 
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
Ramón y Cajal, Teresa
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
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
Mesh: 
Issue Date: 2015
Citation: PLoS ONE.2015;(10)4:e0120020
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.
PMID: 25830658
URI: https://hdl.handle.net/20.500.12530/40460
Rights: openAccess
Appears in Collections:Fundaciones e Institutos de Investigación > IIS H. U. Clínico San Carlos > Artículos

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