Assessing Associations between the AURKA-HMMR-TPX2-TUBG1 Functional Module and Breast Cancer Risk in BRCA1/2 Mutation Carriers
Blanco Guillermo, Ignacio (Institut d'Investigació Biomèdica de Bellvitge)
Kuchenbaecker, Karoline (University of Cambridge)
Cuadras, Daniel (Institut d'Investigació Biomèdica de Bellvitge)
Wang, Xianshu (Mayo Clinic, Rochester, United States of America)
Barrowdale, Daniel (University of Cambridge)
Ruiz de Garibay, Gorka (Institut d'Investigació Biomèdica de Bellvitge)
Librado, Pablo (Universitat de Barcelona)
Sánchez-Gracia, Alejandro (Universitat de Barcelona)
Rozas, Julio (Universitat de Barcelona)
Bonifaci, Núria (Institut d'Investigació Biomèdica de Bellvitge)
McGuffog, Lesley (University of Cambridge)
Pankratz, Vernon S. (Mayo Clinic, Rochester, Minnesota)
Islam, Abul (University of Dhaka)
Mateo, Francesca (Institut d'Investigació Biomèdica de Bellvitge)
Berenguer-Llergo, Antoni (Institut d'Investigació Biomèdica de Bellvitge)
Petit Montserrat, Anna (Institut d'Investigació Biomèdica de Bellvitge)
Català, Isabel (Institut d'Investigació Biomèdica de Bellvitge)
Brunet, Joan (Institut d'Investigació Biomèdica de Girona)
Feliubadaló, Lidia (Institut d'Investigació Biomèdica de Bellvitge)
Tornero, Eva (Institut d'Investigació Biomèdica de Bellvitge)
Benitez, Javier (Centro Nacional de Investigaciones Oncológicas)
Osorio, Ana (Centro Nacional de Investigaciones Oncológicas)
Ramon y Cajal, Teresa (Institut d'Investigació Biomèdica Sant Pau)
Aittomäki, Kristiina (Helsinki University Central Hospital)
Arun, Banu K. (University of Texas)
Toland, Amanda E. (The Ohio State University, Columbus)
Karlan, Beth Y. (Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Los Angeles)
Walsh, Christine (Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Los Angeles)
Lester, Jenny (Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Los Angeles)
Greene, Mark H. (National Cancer Institute, Maryland, Rockville)
Mai, Phuong L. (National Cancer Institute, Maryland, Rockville)
Nussbaum, Robert L. (University of California San Francisco, San Francisco)
Andrulis, Irene L. (Samuel Lunenfeld Research Institute, Mount Sinai Hospital, and Departments of Molecular Genetics and Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada)
Domchek, Susan M. (The University of Pennsylvania School of Medicine, Philadelphia)
Nathanson, Katherine L. (The University of Pennsylvania School of Medicine, Philadelphia)
Rebbeck, Timothy R. (Abramson Cancer Center and Center for Clinical Epidemiology and Biostatistics, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States of America)
Barkardottir, Rosa B. (Landspitali University Hospital (Reykjavík, Islàndia))
Jakubowska, Anna (Pomeranian Medical University, Szczecin)
Lubinski, Jan (Pomeranian Medical University, Szczecin)
Durda, Katarzyna (Pomeranian Medical University, Szczecin)
Jaworska-Bieniek, Katarzyna (Pomeranian Medical University, Szczecin)
Claes, Kathleen (Ghent University, Ghent)
Van Maerken, Tom (Ghent University, Ghent)
Diez, Orland (Vall d'Hebron Institut d'Oncologia)
Hansen, Thomas V. (Copenhagen University Hospital)
Jønson, Lars (Copenhagen University Hospital)
Gerdes, Anne-Marie (Copenhagen University Hospital)
Ejlertsen, Bent (Copenhagen University Hospital)
De la Hoya, Miguel (Instituto de Investigación Sanitaria del Hospital Clínico San Carlos)
Caldes, Trinidad (Instituto de Investigación Sanitaria del Hospital Clínico San Carlos)
Dunning, Alison M. (University of Cambridge)
Oliver, Clare (University of Cambridge)
Fineberg, Elena (University of Cambridge)
Cook, Margaret (University of Cambridge)
Peock, Susan (University of Cambridge)
McCann, Emma (Glan Clwyd Hospital, Rhyl)
Murray, Alex (Singleton Hospital, Swansea)
Jacobs, Chris (Guy's and St. Thomas' National Health Service, London)
Pichert, Gabriella (Guy's and St. Thomas' National Health Service, London)
Lalloo, Fiona (Central Manchester University Hospitals National Health Service, Manchester)
Chu, Carol (Yorkshire Regional Genetics Service, Leeds)
Dorkins, Huw (Kennedy-Galton Centre, Harrow)
Paterson, Joan (Addenbrookes Hospital (Cambridge, Regne Unit))
Ong, Kai-Ren (Birmingham Women's Hospital)
Teixeira, Manuel R. (Universidade do Porto)
Hogervorst, Frans B. L. (The Netherlands Cancer Institute (Amsterdam, Països Baixos))
van der Hout, Annemarie H. (University of Groningen)
Seynaeve, Caroline (Erasmus University Medical Center, Rotterdam)
van der Luijt, Rob B. (University Medical Center Utrecht, Utrecht)
Ligtenberg, Marjolijn J. L. (Radboud university medical center, Nijmegen)
Devilee, Peter (Leiden University Medical Center, Leiden)
Wijnen, Juul T. (Leiden University Medical Center, Leiden)
Rookus, Matti A. (The Netherlands Cancer Institute (Amsterdam, Països Baixos))
Meijers-Heijboer, Hanne E. J. (Vrije Universiteit, Amsterdam)
Blok, Marinus J. (Maastricht University Medical Center)
van den Ouweland, Ans M. W. (Erasmus University Medical Center, Rotterdam)
Aalfs, Cora M. (Department of Clinical Genetics, Amsterdam)
Rodriguez, Gustavo C. (University of Chicago)
Phillips, Kelly-Anne A. (Peter MacCallum Cancer Centre, East Melbourne)
Piedmonte, Marion (Roswell Park Cancer Institute, Buffalo, New York)
Nerenstone, Stacy R. (Hartford Hospital/Helen and Harry Gray Cancer Center)
Bae-Jump, Victoria L. (University of North Carolina)
O'Malley, David M. (Ohio State University, Hilliard)
Ratner, Elena S. (Yale University School of Medicine)
Schmutzler, Rita K. (Uniklinik Köln (Colònia, Alemanya))
Wappenschmidt, Barbara (Uniklinik Köln (Colònia, Alemanya))
Rhiem, Kerstin (University Hospital of Cologne, Cologne, Germany)
Engel, Christoph (University of Leipzig)
Meindl, Alfons (Technical University Munich)
Ditsch, Nina (Ludwig-Maximilian University Munich)
Arnold, Norbert (Kiel University Medical Center Schleswig-Holstein)
Plendl, Hansjoerg J. (Kiel University Medical Center Schleswig-Holstein)
Niederacher, Dieter (University Hospital of Düsseldorf (Alemanya))
Sutter, Christian (Heidelberg University Hospital (Alemanya))
Wang-Gohrke, Shan (University Hospital of Ulm (Alemanya))
Steinemann, Doris (Institute of Cell and Molecular Pathology, Hannover)
Preisler-Adams, Sabine (University of Münster)
Kast, Karin (Technical University Dresden)
Varon-Mateeva, Raymonda (Institute of Human Genetics, Campus Virchov Klinikum, Charite Berlin)
Gehrig, Andrea (Centre of Familial Breast and Ovarian Cancer, Institute of Human Genetics, University Würzburg, Würzburg, Germany)
Bojesen, Anders (Vejle Hospital, Vejle)
Pedersen, Inge Sokilde (Aalborg University Hospital (Dinamarca))
Sunde, Lone (Aarhus University Hospital (Aarhus, Dinamarca))
Jensen, Uffe Birk (Aarhus University Hospital (Aarhus, Dinamarca))
Thomassen, Mads (Odense University Hospital (Dinamarca))
Kruse, Torben A. (Odense University Hospital (Dinamarca))
Foretova, Lenka (Masaryk Memorial Cancer Institute (Brno, República Txeca))
Peterlongo, Paolo (Fondazione Istituto di Oncologia MolecolarE, Milan)
Bernard, Loris (Istituto Europeo di Oncologia, Milan)
Peissel, Bernard (Fondazione Istituto Nazionale Tumori, Milan)
Scuvera, Giulietta (Fondazione Istituto Nazionale Tumori, Milan)
Manoukian, Siranoush (Fondazione Istituto Nazionale Tumori, Milan)
Radice, Paolo (Fondazione Istituto Nazionale Tumori, Milan)
Ottini, Laura ("Sapienza" University, Rome)
Montagna, Marco (Istituto Oncologico Veneto, Padua)
Agata, Simona (Istituto Oncologico Veneto, Padua)
Maugard, Christine (Hopitaux Universitaire de Strasbourg)
Simard, Jacques (Centre Hospitalier Universitaire de Québec Research Center and Laval University, Quebec City)
Soucy, Penny (Centre Hospitalier Universitaire de Québec Research Center and Laval University, Quebec City)
Berger, Andreas (Medical University of Vienna)
Fink-Retter, Anneliese (Medical University of Vienna)
Singer, Christian F. (Medical University of Vienna)
Rappaport, Christine (Medical University of Vienna)
Geschwantler-Kaulich, Daphne (Medical University of Vienna)
Tea, Muy-Kheng (Medical University of Vienna)
Pfeiler, Georg (Medical University of Vienna)
John, Esther M. (Cancer Prevention Institute of California)
Miron, Alex (Dana-Farber Cancer Institute, Boston, Massachusetts)
Neuhausen, Susan L. (Beckman Research Institute of City of Hope (Duarte, Estats Units d'Amèrica))
Terry, Mary Beth (Columbia University)
Chung, Wendy (Columbia University)
Daly, Mary B. (Fox Chase Cancer Center, Philadelphia, Pennsylvania)
Goldgar, David E. (University of Utah School of Medicine, Salt Lake City)
Janavicius, Ramunas (Vilnius University Hospital Santariskiu Clinics)
Dorfling, Cecilia M. (University of Pretoria, Arcadia)
van Rensburg, Elisabeth J. (University of Pretoria, Arcadia)
Fostira, Florentia (National Centre for Scientific Research Demokritos, Athens)
Konstantopoulou, Irene (National Centre for Scientific Research Demokritos, Athens)
Garber, Judy (Harvard Medical School, Boston)
Godwin, Andrew K. (University of Kansas Medical Center, Kansas City)
Olah, Edith (National Institute of Oncology, Budapest)
Narod, Steven A. (University of Toronto)
Rennert, Gad (Clalit National Israeli Cancer Control Center)
Paluch, Shani Shimon (Chaim Sheba Medical Center, Ramat Gan)
Laitman, Yael (Institute of Human Genetics, Ramat Gan)
Friedman, Eitan (Tel Aviv University, Ramat Aviv)
Liljegren, Annelie (Karolinska University Hospital and Karolinska Institutet (Suècia))
Rantala, Johanna (Karolinska University Hospital and Karolinska Institutet (Suècia))
Stenmark-Askmalm, Marie (Linköping University, Sweeden)
Loman, Niklas (Lund University Hospital, Sweeden)
Imyanitov, Evgeny N. (N.N. Petrov Institute of Oncology, St.-Petersburg)
Hamann, Ute (German Cancer Research Center (DKFZ), Heidelberg)
Spurdle, Amanda B. (Queensland Institute of Medical Research (QIMR) Berghofer Medical Research Institute, Brisbane)
Healey, Sue (Queensland Institute of Medical Research (QIMR) Berghofer Medical Research Institute, Brisbane)
Weitzel, Jeffrey N. (Clinical Cancer Genetics, City of Hope, Duarte, California)
Herzog, Josef (Clinical Cancer Genetics, City of Hope, Duarte, California)
Margileth, David (St. Joseph Hospital of Orange, Duarte, California)
Gorrini, Chiara (University Health Network, Toronto)
Esteller, M (Institució Catalana de Recerca i Estudis Avançats)
Gómez Moruno, Antonio (Institut d'Investigació Biomèdica de Bellvitge)
Sayols, Sergi (Institut d'Investigació Biomèdica de Bellvitge)
Vidal, Enrique (Institut d'Investigació Biomèdica de Bellvitge)
Heyn, Holger (Institut d'Investigació Biomèdica de Bellvitge)
Stoppa-Lyonnet, Dominique (Université Paris Descartes, Sorbonne Paris Cité, Paris, France)
Léoné, Melanie (Hospices Civils de Lyon-Centre Léon Bérard, Lyon)
Barjhoux, Laure (Université Lyon 1)
Fassy-Colcombet, Marion (Institut Curie, Paris)
De Pauw, Antoine (Institut Curie, Paris)
Lasset, Christine (Université Lyon 1)
Ferrer, Sandra Fert (Hôtel Dieu Centre Hospitalier, Chambéry)
Castera, Laurent (Department of Tumour Biology, Institut Curie, Paris)
Berthet, Pascaline (Centre François Baclesse, Caen, France)
Cornelis, François (Genetic Unit, Avicenne Hospital, Clermont-Ferrand)
Bignon, Yves-Jean (Université de Clermont-Ferrand)
Damiola, Francesca (Centre de Recherche en Cancérologie de Lyon)
Mazoyer, Sylvie (Centre de Recherche en Cancérologie de Lyon)
Sinilnikova, Olga M. (Centre de Recherche en Cancérologie de Lyon)
Maxwell, Christopher A. (University of British Columbia, Vancouver)
Vijai, Joseph (Memorial Sloan-Kettering Cancer Center, New York)
Robson, Mark (Memorial Sloan-Kettering Cancer Center, New York)
Kauff, Noah (Memorial Sloan-Kettering Cancer Center, New York)
Corines, Marina (Memorial Sloan-Kettering Cancer Center, New York)
Villano, Danylko (Memorial Sloan-Kettering Cancer Center, New York)
Cunningham, Julie M. (Mayo Clinic, Rochester, Minnesota, United States of America)
Lee, Adam (Mayo Clinic, Rochester, Minnesota)
Lindor, Noralane (Mayo Clinic, Scottsdale, Arizona)
Lazaro Garcia, Conxi (Institut d'Investigació Biomèdica de Bellvitge)
Easton, Douglas F. (University of Cambridge)
Offit, Kenneth (Memorial Sloan-Kettering Cancer Center, New York)
Chenevix-Trench, Georgia (Queensland Institute of Medical Research, Brisbane, Australia)
Couch, Fergus J. (Mayo Clinic, Rochester, Minnesota)
Antoniou, Antonis C. (University of Cambridge)
Pujana, Miguel Angel (Institut d'Investigació Biomèdica de Bellvitge)

Data:	2015
Resum:	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 p 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.
Ajuts:	Instituto de Salud Carlos III RTICC 06/0020/1060 Instituto de Salud Carlos III FISPI08/1120 Instituto de Salud Carlos III SAF2010-20493 Instituto de Salud Carlos III RD12/00369/0006 Instituto de Salud Carlos III RD12/00539 Instituto de Salud Carlos III PI10/01422 Instituto de Salud Carlos III PI12/01528 Instituto de Salud Carlos III PI13/00285 Instituto de Salud Carlos III RD12/0036/0008 Agència de Gestió d'Ajuts Universitaris i de Recerca 2009/SGR-290 Agència de Gestió d'Ajuts Universitaris i de Recerca 2009/SGR-293
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons en que s'entrega l'obra al domini públic. Podeu copiar, modificar, distribuir l'obra i fer-ne comunicació pública, fins i tot amb finalitat comercial, sense demanar cap mena de permís.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	PloS one, Vol. 10 (april 2015) , ISSN 1932-6203

DOI: 10.1371/journal.pone.0120020
PMID: 25830658

18 p, 1.0 MB

El registre apareix a les col·leccions:
Documents de recerca > Documents dels grups de recerca de la UAB > Centres i grups de recerca (producció científica) > Ciències de la salut i biociències > Institut de Recerca Sant Pau
Articles > Articles de recerca
Articles > Articles publicats