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BMC Cancer
Published in: BMC Cancer 1/2018

Open Access 01-12-2018 | Research article

Receptor activator of nuclear factor kB ligand, osteoprotegerin, and risk of death following a breast cancer diagnosis: results from the EPIC cohort

Authors: Danja Sarink, Helena Schock, Theron Johnson, Jenny Chang-Claude, Kim Overvad, Anja Olsen, Anne Tjønneland, Patrick Arveux, Agnès Fournier, Marina Kvaskoff, Heiner Boeing, Anna Karakatsani, Antonia Trichopoulou, Carlo La Vecchia, Giovanna Masala, Claudia Agnoli, Salvatore Panico, Rosario Tumino, Carlotta Sacerdote, Carla H. van Gils, Petra H. M. Peeters, Elisabete Weiderpass, Antonio Agudo, Miguel Rodríguez-Barranco, José María Huerta, Eva Ardanaz, Leire Gil, Kay Tee Kaw, Julie A. Schmidt, Laure Dossus, Mathilde His, Dagfinn Aune, Elio Riboli, Rudolf Kaaks, Renée T. Fortner

Published in: BMC Cancer | Issue 1/2018

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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.
Appendix
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Metadata
Title
Receptor activator of nuclear factor kB ligand, osteoprotegerin, and risk of death following a breast cancer diagnosis: results from the EPIC cohort
Authors
Danja Sarink
Helena Schock
Theron Johnson
Jenny Chang-Claude
Kim Overvad
Anja Olsen
Anne Tjønneland
Patrick Arveux
Agnès Fournier
Marina Kvaskoff
Heiner Boeing
Anna Karakatsani
Antonia Trichopoulou
Carlo La Vecchia
Giovanna Masala
Claudia Agnoli
Salvatore Panico
Rosario Tumino
Carlotta Sacerdote
Carla H. van Gils
Petra H. M. Peeters
Elisabete Weiderpass
Antonio Agudo
Miguel Rodríguez-Barranco
José María Huerta
Eva Ardanaz
Leire Gil
Kay Tee Kaw
Julie A. Schmidt
Laure Dossus
Mathilde His
Dagfinn Aune
Elio Riboli
Rudolf Kaaks
Renée T. Fortner
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2018
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-018-4887-3

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