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Title: Receptor activator of nuclear factor kB ligand, osteoprotegerin, and risk of death following a breast cancer diagnosis: results from the EPIC cohort
Author: Sarink, Danja
Schock, Helena
Johnson, Theron
Chang-Claude, Jenny
Overvad, Kim
Olsen, Anja
Tjønneland, Anne
Arveux, Patrick
Fournier, Agnès
Kvaskoff, Marina
Boeing, Heiner
Karakatsani, Anna
Trichopoulou, Antonia
Vecchia, Carlo La
Masala, Giovanni
Agnoli, Claudia
Panico, Salvatore
Tumino, Rosario
Sacerdote, Carlotta
van Gils, Carla H.
Peeters, Petra H. M.
Weiderpass, Elisabete
Agudo, Antonio
Rodríguez Barranco, Miguel
Huerta Castaño, José María
Ardanaz, Eva
Gil, Leire
Kaw, Kay Tee
Schmidt, Julie A.
Dossus, Laure
His, Mathilde
Aune, Dagfinn
Riboli, Elio
Kaaks, Rudolf
Fortner, Renée T.
Keywords: Càncer de mama
Breast cancer
Issue Date: 22-Oct-2018
Publisher: BioMed Central
Abstract: Background: 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. Methods: 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. Results: 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. Conclusions: 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.
Note: Reproducció del document publicat a:
It is part of: BMC Cancer, 2018, vol. 18
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Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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