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

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Title: Osteoprotegerin and breast cancer risk by hormone receptor subtype: a nested case-control study in the EPIC cohort.
Authors: Fortner, RT
Sarink, D
Schock, H
Johnson, T
Tjonneland, A
Olsen, A
Overvad, K
Affret, A
His, M
Boutron-Ruault, M
Boeing, H
Trichopoulou, A
Naska, A
Orfanos, P
Palli, D
Sieri, S
Mattiello, A
Tumino, R
Ricceri, F
Bueno-de-Mequita, H
Peeters, PHM
Van Gils, CH
Weiderpass, E
Lund, E
Ramon Quiros, J
Agudo, A
Sanchez, M
Chirlaque, M
Ardanaz, E
Dorronsoro, M
Key, T
Khaw, K
Rinaldi, S
Dossus, L
Gunter, M
Merritt, MA
Riboli, E
Kaaks, R
Item Type: Journal Article
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.
Issue Date: 8-Feb-2017
Date of Acceptance: 10-Jan-2017
URI: http://hdl.handle.net/10044/1/44512
DOI: https://dx.doi.org/10.1186/s12916-017-0786-8
ISSN: 1741-7015
Publisher: BioMed Central
Journal / Book Title: BMC Medicine
Volume: 15
Copyright Statement: © The Author(s). 2017.Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated
Sponsor/Funder: University Medical Center Utrecht
Imperial College Trust
Funder's Grant Number: N/A
P47328
Keywords: Breast cancer
Estrogen receptor
Hormone receptor
Osteoprotegerin
Progesterone receptor
RANK axis
General & Internal Medicine
11 Medical And Health Sciences
Publication Status: Published
Article Number: 26
Appears in Collections:Faculty of Medicine
Epidemiology, Public Health and Primary Care



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