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dc.contributor.authorSarink, Danja
dc.contributor.authorSchock, Helena
dc.contributor.authorJohnson, Theron
dc.contributor.authorChang-Claude, Jenny
dc.contributor.authorOvervad, Kim
dc.contributor.authorOlsen, Anja
dc.contributor.authorTjønneland, Anne
dc.contributor.authorArveux, Patrick
dc.contributor.authorFournier, Agnès
dc.contributor.authorKvaskoff, Marina
dc.contributor.authorBoeing, Heiner
dc.contributor.authorKarakatsani, Anna
dc.contributor.authorTrichopoulou, Antonia
dc.contributor.authorLa Vecchia, Carlo
dc.contributor.authorMasala, Giovanna
dc.contributor.authorAgnoli, Claudia
dc.contributor.authorPanico, Salvatore
dc.contributor.authorTumino, Rosario
dc.contributor.authorSacerdote, Carlotta
dc.contributor.authorvan Gils, Carla H.
dc.contributor.authorPeeters, Petra H.M.
dc.contributor.authorWeiderpass, Elisabete
dc.contributor.authorAgudo, Antonio
dc.contributor.authorRodríguez-Barranco, Miguel
dc.contributor.authorHuerta, José María
dc.contributor.authorArdanaz, Eva
dc.contributor.authorGil, Leire
dc.contributor.authorKaw, Kay Tee
dc.contributor.authorSchmidt, Julie A.
dc.contributor.authorDossus, Laure
dc.contributor.authorHis, Mathilde
dc.contributor.authorAune, Dagfinn
dc.contributor.authorRiboli, Elio
dc.contributor.authorKaaks, Rudolf
dc.contributor.authorFortner, Renée T.
dc.date.accessioned2019-07-17T08:21:50Z
dc.date.available2019-07-17T08:21:50Z
dc.date.issued2018-10-22
dc.description.abstract<b>Background</b><br> Receptor activator of nuclear factor kappa-B (RANK)-signaling is involved in tumor growth and spread in experimental models. Binding of RANK ligand (RANKL) to RANK activates signaling, which is inhibited by osteoprotegerin (OPG). We have previously shown that circulating soluble RANKL (sRANKL) and OPG are associated with breast cancer risk. Here we extend these findings to provide the first data on pre-diagnosis concentrations of sRANKL and OPG and risk of breast cancer-specific and overall mortality after a breast cancer diagnosis.<br> <b>Methods</b><br> Two thousand six pre- and postmenopausal women with incident invasive breast cancer (1620 (81%) with ER+ disease) participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort were followed-up for mortality. Pre-diagnosis concentrations of sRANKL and OPG were quantified in baseline serum samples using an enzyme-linked immunosorbent assay and electrochemiluminescent assay, respectively. Hazard ratios (HRs) and 95% confidence intervals (CIs) for breast cancer-specific and overall mortality were calculated using Cox proportional hazards regression models.<br> <b>Results</b><br> Especially in women with ER+ disease, higher circulating OPG concentrations were associated with higher risk of breast cancer-specific (quintile 5 vs 1 HR 1.77 [CI 1.03, 3.04]; ptrend 0.10) and overall mortality (q5 vs 1 HR 1.39 [CI 0.94, 2.05]; ptrend 0.02). sRANKL and the sRANKL/OPG ratio were not associated with mortality following a breast cancer diagnosis.<br> <b>Conclusions</b><br> High pre-diagnosis endogenous concentrations of OPG, the decoy receptor for RANKL, were associated with increased risk of death after a breast cancer diagnosis, especially in those with ER+ disease. These results need to be confirmed in well-characterized patient cohorts.en_US
dc.description.sponsorshipThis project was funded by research grant #111454 from the Deutsche Kresbshilfe. RT Fortner was supported by a Marie Curie International Incoming Fellowship of the European Commission’s Seventh Framework Programme (MC-IIF-623984).<br>The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF); the Hellenic Health Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); ERC-2009-AdG 232997 and Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health (Norway); Health Research Fund (FIS), PI13/00061 to Granada;, PI13/01162 to EPIC-Murcia), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, ISCIII RETIC (RD06/0020) (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden); Cancer Research UK (14136 to EPIC-Norfolk; C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (United Kingdom).en_US
dc.descriptionPublished version, available at: <a href=https://doi.org/10.1186/s12885-018-4887-3>https://doi.org/10.1186/s12885-018-4887-3</a>en_US
dc.identifier.citationSarink, D., Schock, H., Johnson, T., Chang-Claude, J., Overvad, K., Olsen, A., Tjønneland, A., Arveux, P., Fournier, A., Kvaskoff, M., Boeing, H., Karakatsani, A., Trichopoulou, A., La Vecchia, C., Masala, G., Agnoli, C,, Panico, S., Tumino, R., Sacerdote, C., van Gils, C.H., Peeters, P.H., Weiderpass, E., Agudo, A., Rodríguez-Barranco, M., Huerta, J.M., Ardanaz, E., Gil, L., Te Kaw, K., Schmidt, J.A., Dossus, L., His, M., Aune, D., Riboli, E., Kaaks, R., Fortner, R.T. (2018) Receptor activator of nuclear factor kB ligand, osteoprotegerin, and risk of death following a breast cancer diagnosis: results from the EPIC cohort. <i> BMC Cancer, 2018;18:1010</i>, 11s. http://dx.doi.org/10.1186/s12885-018-4887-3en_US
dc.identifier.issn1471-2407
dc.identifier.otherFRIDAID 1641302
dc.identifier.other10.1186/s12885-018-4887-3
dc.identifier.urihttps://hdl.handle.net/10037/15770
dc.language.isoengen_US
dc.publisherSpringer Nature, BMCen_US
dc.relation.isbasedonFor information on how to submit an application for gaining access to EPIC data and/or biospecimens, please follow the instructions at: <a href=http://epic.iarc.fr/access/index.php>http://epic.iarc.fr/access/index.php</a>en_US
dc.relation.journalBMC Cancer
dc.rights.accessRightsopenAccessen_US
dc.subjectVDP::Medical disciplines: 700::Clinical medical disciplines: 750::Oncology: 762en_US
dc.subjectVDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Onkologi: 762en_US
dc.titleReceptor activator of nuclear factor kB ligand, osteoprotegerin, and risk of death following a breast cancer diagnosis: results from the EPIC cohorten_US
dc.typeJournal articleen_US
dc.typePeer revieweden_US


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