Τίτλος:
Receptor activator of nuclear factor kB ligand, osteoprotegerin, and risk of death following a breast cancer diagnosis: Results from the EPIC cohort
Περίληψη:
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. © 2018 The Author(s).
Συγγραφείς:
Sarink, 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.M.
Weiderpass, E.
Agudo, A.
Rodríguez-Barranco, M.
Huerta, J.M.
Ardanaz, E.
Gil, L.
Kaw, K.T.
Schmidt, J.A.
Dossus, L.
His, M.
Aune, D.
Riboli, E.
Kaaks, R.
Fortner, R.T.
Λέξεις-κλειδιά:
osteoprotegerin; receptor activator of nuclear factor kappa B; osteoclast differentiation factor; osteoprotegerin, adult; aged; all cause mortality; Article; blood sampling; breast cancer; cancer diagnosis; cancer incidence; cancer mortality; cancer specific survival; cohort analysis; concentration (parameters); confidence interval; controlled study; electrochemiluminescence; enzyme linked immunosorbent assay; estrogen receptor positive breast cancer; female; follow up; hazard ratio; human; major clinical study; mortality risk; postmenopause; premenopause; proportional hazards model; sensitivity analysis; tumor invasion; blood; breast tumor; case control study; limit of detection; metabolism; middle aged; mortality; prognosis; risk, Adult; Aged; Breast Neoplasms; Case-Control Studies; Cohort Studies; Female; Humans; Limit of Detection; Middle Aged; Osteoprotegerin; Prognosis; RANK Ligand; Risk
