RT Journal Article
T1 Receptor activator of nuclear factor kB ligand, osteoprotegerin, and risk of death following a breast cancer diagnosis: results from the EPIC cohort.
A1 Sarink, Danja
A1 Schock, Helena
A1 Johnson, Theron
A1 Chang-Claude, Jenny
A1 Overvad, Kim
A1 Olsen, Anja
A1 Tjønneland, Anne
A1 Arveux, Patrick
A1 Fournier, Agnès
A1 Kvaskoff, Marina
A1 Boeing, Heiner
A1 Karakatsani, Anna
A1 Trichopoulou, Antonia
A1 La Vecchia, Carlo
A1 Masala, Giovanna
A1 Agnoli, Claudia
A1 Panico, Salvatore
A1 Tumino, Rosario
A1 Sacerdote, Carlotta
A1 van Gils, Carla H
A1 Peeters, Petra H M
A1 Weiderpass, Elisabete
A1 Agudo, Antonio
A1 Rodríguez-Barranco, Miguel
A1 Huerta, José María
A1 Ardanaz, Eva
A1 Gil, Leire
A1 Kaw, Kay Tee
A1 Schmidt, Julie A
A1 Dossus, Laure
A1 His, Mathilde
A1 Aune, Dagfinn
A1 Riboli, Elio
A1 Kaaks, Rudolf
A1 Fortner, Renée T
K1 Breast cancer
K1 Epidemiology
K1 Reproductive, hormonal, and related factors
K1 Serum biomarkers of endogenous exposures
AB 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. 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. 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. 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.
YR 2018
FD 2018-10-22
LK http://hdl.handle.net/10668/13117
UL http://hdl.handle.net/10668/13117
LA en
DS RISalud
RD Apr 10, 2025