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BMC Medicine
Published in: BMC Medicine 1/2017

Open Access 01-12-2017 | Research article

Osteoprotegerin and breast cancer risk by hormone receptor subtype: a nested case-control study in the EPIC cohort

Authors: Renée T. Fortner, Danja Sarink, Helena Schock, Theron Johnson, Anne Tjønneland, Anja Olsen, Kim Overvad, Aurélie Affret, Mathilde His, Marie-Christine Boutron-Ruault, Heiner Boeing, Antonia Trichopoulou, Androniki Naska, Philippos Orfanos, Domenico Palli, Sabina Sieri, Amalia Mattiello, Rosario Tumino, Fulvio Ricceri, H. Bas Bueno-de-Mesquita, Petra H. M. Peeters, Carla H. Van Gils, Elisabete Weiderpass, Eiliv Lund, J. Ramón Quirós, Antonio Agudo, Maria-José Sánchez, María-Dolores Chirlaque, Eva Ardanaz, Miren Dorronsoro, Tim Key, Kay-Tee Khaw, Sabina Rinaldi, Laure Dossus, Marc Gunter, Melissa A. Merritt, Elio Riboli, Rudolf Kaaks

Published in: BMC Medicine | Issue 1/2017

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Abstract

Background

Circulating osteoprotegerin (OPG), a member of the receptor activator of nuclear factor kappa-B (RANK) axis, may influence breast cancer risk via its role as the decoy receptor for both the RANK ligand (RANKL) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Circulating OPG and breast cancer risk has been examined in only one prior study.

Methods

A case-control study was nested in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. A total of 2008 incident invasive breast cancer cases (estrogen receptor (ER)+, n = 1622; ER–, n = 386), matched 1:1 to controls, were included in the analysis. Women were predominantly postmenopausal at blood collection (77%); postmenopausal women included users and non-users of postmenopausal hormone therapy (HT). Serum OPG was quantified with an electrochemiluminescence assay. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression.

Results

The associations between OPG and ER+ and ER– breast cancer differed significantly. Higher concentrations of OPG were associated with increased risk of ER– breast cancer (top vs. bottom tertile RR = 1.93 [95% CI 1.24–3.02]; p trend = 0.03). We observed a suggestive inverse association for ER+ disease overall and among women premenopausal at blood collection. Results for ER– disease did not differ by menopausal status at blood collection (p het = 0.97), and we observed no heterogeneity by HT use at blood collection (p het ≥ 0.43) or age at breast cancer diagnosis (p het ≥ 0.30).

Conclusions

This study provides the first prospective data on OPG and breast cancer risk by hormone receptor subtype. High circulating OPG may represent a novel risk factor for ER– breast cancer.
Appendix
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Metadata
Title
Osteoprotegerin and breast cancer risk by hormone receptor subtype: a nested case-control study in the EPIC cohort
Authors
Renée T. Fortner
Danja Sarink
Helena Schock
Theron Johnson
Anne Tjønneland
Anja Olsen
Kim Overvad
Aurélie Affret
Mathilde His
Marie-Christine Boutron-Ruault
Heiner Boeing
Antonia Trichopoulou
Androniki Naska
Philippos Orfanos
Domenico Palli
Sabina Sieri
Amalia Mattiello
Rosario Tumino
Fulvio Ricceri
H. Bas Bueno-de-Mesquita
Petra H. M. Peeters
Carla H. Van Gils
Elisabete Weiderpass
Eiliv Lund
J. Ramón Quirós
Antonio Agudo
Maria-José Sánchez
María-Dolores Chirlaque
Eva Ardanaz
Miren Dorronsoro
Tim Key
Kay-Tee Khaw
Sabina Rinaldi
Laure Dossus
Marc Gunter
Melissa A. Merritt
Elio Riboli
Rudolf Kaaks
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Medicine / Issue 1/2017
Electronic ISSN: 1741-7015
DOI
https://doi.org/10.1186/s12916-017-0786-8

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