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@article{Sarink:2018:10.1186/s12885-018-4887-3,
author = {Sarink, D and Schock, H and Johnson, T and Chang-Claude, J and Overvad, K and Olsen, A and Tjonneland, A and Arveux, P and Fournier, A and Kvaskoff, M and Boeing, H and Karakatsani, A and Trichopoulou, A and La, Vecchia C and Masala, G and Agnoli, C and Panico, S and Tumino, R and Sacerdote, C and van, Gils CH and Peeters, PHM and Weiderpass, E and Agudo, A and Rodriguez-Barranco, M and Maria, Huerta J and Ardanaz, E and Gil, L and Kaw, KT and Schmidt, JA and Dossus, L and His, M and Aune, D and Riboli, E and Kaaks, R and Fortner, RT},
doi = {10.1186/s12885-018-4887-3},
journal = {BMC Cancer},
title = {Receptor activator of nuclear factor kB ligand, osteoprotegerin, and risk of death following a breast cancer diagnosis: results from the EPIC cohort},
url = {http://dx.doi.org/10.1186/s12885-018-4887-3},
volume = {18},
year = {2018}
}

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TY  - JOUR
AB  - BackgroundReceptor 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.MethodsTwo 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.ResultsEspecially 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.ConclusionsHigh 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.
AU  - Sarink,D
AU  - Schock,H
AU  - Johnson,T
AU  - Chang-Claude,J
AU  - Overvad,K
AU  - Olsen,A
AU  - Tjonneland,A
AU  - Arveux,P
AU  - Fournier,A
AU  - Kvaskoff,M
AU  - Boeing,H
AU  - Karakatsani,A
AU  - Trichopoulou,A
AU  - La,Vecchia C
AU  - Masala,G
AU  - Agnoli,C
AU  - Panico,S
AU  - Tumino,R
AU  - Sacerdote,C
AU  - van,Gils CH
AU  - Peeters,PHM
AU  - Weiderpass,E
AU  - Agudo,A
AU  - Rodriguez-Barranco,M
AU  - Maria,Huerta J
AU  - Ardanaz,E
AU  - Gil,L
AU  - Kaw,KT
AU  - Schmidt,JA
AU  - Dossus,L
AU  - His,M
AU  - Aune,D
AU  - Riboli,E
AU  - Kaaks,R
AU  - Fortner,RT
DO  - 10.1186/s12885-018-4887-3
PY  - 2018///
SN  - 1471-2407
TI  - Receptor activator of nuclear factor kB ligand, osteoprotegerin, and risk of death following a breast cancer diagnosis: results from the EPIC cohort
T2  - BMC Cancer
UR  - http://dx.doi.org/10.1186/s12885-018-4887-3
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000447995300003&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/65209
VL  - 18
ER  -

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