Journal article

Assessing Associations between the AURKA-HMMR-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 Sanchez-Gracia, Julio Rozas, Nuria Bonifaci, Lesley McGuffog, Vernon S Pankratz, Abul Islam, Francesca Mateo, Antoni Berenguer, Anna Petit, Isabel Catala, Joan Brunet, Lidia Feliubadalo, Eva Tornero Show all

PLOS ONE | PUBLIC LIBRARY SCIENCE | Published : 2015

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 haz..

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Awarded by National Cancer Institute


Awarded by Lithuania (BFBOCC-LT): Research Council of Lithuania grant


Awarded by LSC grant


Awarded by ESF


Awarded by Spanish Association against Cancer


Awarded by Hereditary Cancer Research Registry from the National Cancer Institute and the Office of the Director, National Institutes of Health


Awarded by Cancer Research-United Kingdom grant


Awarded by Cancer Research United Kingdom Grants


Awarded by Cancer Research United Kingdom Grant


Awarded by University of Kansas Cancer Center


Awarded by AKG


Awarded by German Cancer Aid


Awarded by National Cancer Institute grant


Awarded by GOG Statistical and Data Center


Awarded by GOG's Cancer Prevention and Control Committee


Awarded by ISCIII (Spain)


Awarded by Academy of Finland


Awarded by Dutch Cancer Society grant


Awarded by Netherlands Organization of Scientific Research


Awarded by Pink Ribbon grant


Awarded by BBMRI grant


Awarded by Hungarian Research Grant


Awarded by Norwegian EEA Financial Mechanism


Awarded by Spanish Ministry of Health ISCIII FIS


Awarded by RTICC


Awarded by AGAUR Generalitat de Catalunya


Awarded by Canadian Breast Cancer Research Alliance-grant


Awarded by Ministry of Economic Development, Innovation and Export Trade-grant


Awarded by National Institutes of Health grant


Awarded by NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer


Awarded by United States Department of Defence Ovarian Cancer Idea award


Awarded by State Budget of the Czech Republic (RECAMO)


Awarded by MH CZ-DRO (MMCI)


Awarded by NAROD


Awarded by NCI Intramural Research Program, National Institutes of Health


Awarded by Russian Federation for Basic Research


Awarded by Federal Agency for Science and Innovations, Russia


Awarded by Canadian Institutes of Health Research for the "CIHR Team in Familial Risks of Breast Cancer" program and grant from the National Cancer Institute


Awarded by National Institutes of Health (NIH)


Awarded by American Cancer Society Early Detection Professorship



Awarded by Cancer Research UK


Awarded by National Breast Cancer Foundation


Awarded by NATIONAL CANCER INSTITUTE


Funding Acknowledgements

BCFR-all. This work was supported by grant UM1 CA164920 from the National Cancer Institute. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the United States Government or the BCFR. BFBOCC: BFBOCC is supported by: Lithuania (BFBOCC-LT): Research Council of Lithuania grant LIG-07/2012 and Hereditary Cancer Association (Paveldimo vezio asociacija); Latvia (BFBOCC-LV) is partly supported by LSC grant 10.0010.08 and in part by a grant from the ESF Nr. 2009/0220/1DP/1.1.1.2.0/09/APIA/VIAA/016 and Liepaja's municipal council. BMBSA: BRCA-gene mutations and breast cancer in South African women (BMBSA) was supported by grants from the Cancer Association of South Africa (CANSA) to EJR. BRICOH: SLN was partially supported by the Morris and Horowitz Familes Endowed Professorship. CBCS: This work was supported by the NEYE Foundation. CNIO: This work was partially supported by Spanish Association against Cancer (AECC08), RTICC 06/0020/1060, FISPI08/1120, Mutua Madrilena Foundation (FMMA) and SAF2010-20493. COH-CCGCRN: City of Hope Clinical Cancer Genetics Community Network and the Hereditary Cancer Research Registry, supported in part by Award Number RC4CA153828 (PI: JW) from the National Cancer Institute and the Office of the Director, National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. CONSIT TEAM: Funds from Italian citizens who allocated the 5x1000 share of their tax payment in support of the Fondazione IRCCS Istituto Nazionale Tumori, according to Italian laws (INT-Institutional strategic projects '5x1000') to SM. Italian Association for Cancer Research (AIRC) to LO. CORE: The CIMBA data management and data analysis were supported by Cancer Research-United Kingdom grants C12292/A11174 and C1287/A10118. SH is supported by an NHMRC Program Grant to GCT. ACA is a Cancer Research -United Kingdom Senior Cancer Research Fellow. GCT is an NHMRC Senior Principal Research Fellow. DKFZ: The DKFZ study was supported by the DKFZ. DEMOKRITOS: This research has been co-financed by the European Union (European Social Fund-ESF) and Greek national funds through the Operational Program "Education and Lifelong Learning" of the National Strategic Reference Framework (NSRF)-Research Funding Program of the General Secretariat for Research & Technology: ARISTEIA. Investing in knowledge society through the European Social Fund. EMBRACE: EMBRACE is supported by Cancer Research United Kingdom Grants C1287/A10118 and C1287/A11990. DGE and FL are supported by an National Institute of Health Research (NIHR) grant to the Biomedical Research Centre, Manchester. The Investigators at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust are supported by an NIHR grant to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. RE and EB are supported by Cancer Research United Kingdom Grant C5047/A8385. FCCC: The authors acknowledge support from The University of Kansas Cancer Center (P30 CA168524) and the Kansas Bioscience Authority Eminent Scholar Program. AKG was funded by 5U01CA113916, R01CA140323, and by the Chancellors Distinguished Chair in Biomedical Sciences Professorship.GC-HBOC: The German Consortium of Hereditary Breast and Ovarian Cancer (GC-HBOC) is supported by the German Cancer Aid (grant no 109076, RKS) and by the Center for Molecular Medicine Cologne (CMMC). GEMO: The study was supported by the Ligue National Contre le Cancer; the Association "Le cancer du sein, parlonsen!" Award; and the Canadian Institutes of Health Research for the "CIHR Team in Familial Risks of Breast Cancer" program. G-FAST: TVM is a postdoctoral researcher funded by the Fund for Scientific Research Flanders (FWO). GOG: This study was supported by National Cancer Institute grants to the Gynecologic Oncology Group (GOG) Administrative Office and Tissue Bank (CA 27469), the GOG Statistical and Data Center (CA 37517), and GOG's Cancer Prevention and Control Committee (CA 101165). MHG, PLM and Dr. Savage were supported by funding from the Intramural Research Program, NCI. HCSC: Was supported by a grant RD12/00369/0006 and 12/00539 from ISCIII (Spain), partially supported by European Regional Development FEDER funds. HEBCS: The HEBCS was financially supported by the Helsinki University Central Hospital Research Fund, Academy of Finland (132473), the Finnish Cancer Society and the Sigrid Juselius Foundation. HEBON: The HEBON study is supported by the Dutch Cancer Society grants NKI1998-1854, NKI2004-3088, NKI2007-3756, the Netherlands Organization of Scientific Research grant NWO 91109024, the Pink Ribbon grant 110005 and the BBMRI grant NWO 184.021.007/CP46. HUNBOCS: Hungarian Breast and Ovarian Cancer Study was supported by Hungarian Research Grant KTIA-OTKA CK-80745 and the Norwegian EEA Financial Mechanism HU0115/NA/2008-3/OP-9. ICO: The ICO-IDIBELL study was supported by grants from the Spanish Ministry of Health ISCIII FIS (PI10/01422, PI12/01528, and PI13/00285) and RTICC (RD12/0036/0008); the Ramon Areces (XV), Eugenio Rodriguez Pascual (2012), and Roses Contra el Cancer (2012) Foundations; the Spanish Association Against Cancer (AECC 2010); and the AGAUR Generalitat de Catalunya (2009-SGR290 and 2009-SGR293). IHCC: The IHCC was supported by Grant PBZ_KBN_122/P05/2004; Katarzyna Jaworska is a fellow of International PhD program, Postgraduate School of Molecular Medicine, Warsaw Medical University, supported by the Polish Foundation of Science. ILUH: The ILUH group was supported by the Icelandic Association "Walking for Breast Cancer Research", by the Nordic Cancer Union and by the Landspitali University Hospital Research Fund. INHERIT: This work was supported by the Canadian Institutes of Health Research for the "CIHR Team in Familial Risks of Breast Cancer" program, the Canadian Breast Cancer Research Alliance-grant #019511 and the Ministry of Economic Development, Innovation and Export Trade-grant #PSR-SIIRI-701. IOVHBOCS: The study was supported by Ministero dell'Istruzione, dell'Universita e della Ricerca and Ministero della Salute. IPOBCS: This study was in part supported by Liga Portuguesa Contra o Cancro. KCONFAB: kConFab is supported by grants from the National Breast Cancer Foundation, the National Health and Medical Research Council (NHMRC) and by the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia. GCT and ABS are NHMRC Senior Research Fellows.MAYO: MAYO is supported by National Institutes of Health grant CA128978, an NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), a United States Department of Defence Ovarian Cancer Idea award (W81XWH-10-1-0341) and grants from the Breast Cancer Research Foundation. MCGILL: Jewish General Hospital Weekend to End Breast Cancer, Quebec Ministry of Economic Development, Innovation and Export Trade. MODSQUAD: The work was supported by the European Regional Development Fund and the State Budget of the Czech Republic (RECAMO, CZ.1.05/2.1.00/03.0101) and MH CZ-DRO (MMCI, 00209805). MSKCC: MSKCC is supported by Breast Cancer Research Foundation, the Niehaus Family Genetics Research Fund, and the STARR Cancer Consortium Grants. NAROD: 1R01 CA149429-01. NCI: The research of MHG and PLM was supported by the NCI Intramural Research Program, National Institutes of Health, and by support services contracts NO2-CP-11019-50 and N02-CP-65504 with Westat, Inc, Rockville, Maryland. This study was supported by National Cancer Institute grants to the Gynecologic Oncology Group (GOG) Administrative Office and Tissue Bank (CA 27469), the GOG Statistical and Data Center (CA 37517), and GOG's Cancer Prevention and Control Committee (CA 101165). NICCC: NICCC is supported by Clalit Health Services in Israel. Some of it's activities are supported by the Israel Cancer Association and the Breast Cancer Research Foundation (BCRF), New York. NNPIO: This work has been supported by the Russian Federation for Basic Research (grants 11-04-00227, 12-04-00928 and 12-04-01490) and the Federal Agency for Science and Innovations, Russia (contract 02.740.11.0780). OCGN: This work was supported by the Canadian Institutes of Health Research for the "CIHR Team in Familial Risks of Breast Cancer" program and grant UM1 CA164920 from the National Cancer Institute. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the United States Government or the BCFR. OSUCCG: OSUCCG is supported by the Ohio State University Comprehensive Cancer Center. SMC: This project was partially funded through a grant by the Isreal cancer association and the funding for the Israeli Inherited breast cancer consortium. SWE-BRCA: SWE-BRCA collaborators are supported by the Swedish Cancer Society. UCHICAGO: UCHICAGO is supported by NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA125183), R01 CA142996, 1U01CA161032 and by the Ralph and Marion Falk Medical Research Trust, the Entertainment Industry Fund National Women's Cancer Research Alliance and the Breast Cancer research Foundation. OIO is an ACS Clinical Research Professor. UCSF: UCSF Cancer Risk Program and Helen Diller Family Comprehensive Cancer Center. UPENN: National Institutes of Health (NIH) (R01-CA102776 and R01-CA083855; Breast Cancer Research Foundation; Rooney Family Foundation; Susan G. Komen Foundation for the cure, Basser Research Center for BRCA. WCP: The Women's Cancer Program (WCP) at the Samuel Oschin Comprehensive Cancer Institute is funded by the American Cancer Society Early Detection Professorship (SIOP-06-258-01-COUN). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.