@misc{10481/49844,
year = {2017},
url = {http://hdl.handle.net/10481/49844},
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];
ptrend = 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
(phet = 0.97), and we observed no heterogeneity by HT use at blood collection (phet ≥ 0.43) or age at breast cancer
diagnosis (phet ≥ 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.},
organization = {This project was funded by research grant 111454 from the Deutsche Kresbshilfe.
RT Fortner was supported by a Marie Curie International Incoming Fellowship of
the European Commission’s Seventh Framework Programme (MC-IIF-623984).
The coordination of EPIC is financially supported by the European
Commission (DG-SANCO) and the International Agency for Research on
Cancer. The national cohorts are supported by the Danish Cancer Society
(Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle
Générale de l’Education Nationale, and Institut National de la Santé et de la
Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer
Research Center (DKFZ), Federal Ministry of Education and Research (BMBF),
Deutsche Krebshilfe, Deutsches Krebsforschungszentrum, and Federal
Ministry of Education and Research (Germany); the Hellenic Health
Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy
and the National Research Council (Italy); the Dutch Ministry of Public Health,
Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research
Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World
Cancer Research Fund (WCRF), and Statistics Netherlands (The Netherlands);
ERC-2009-AdG 232997 and Nordforsk, Nordic Centre of Excellence programme
on Food, Nutrition and Health (Norway); Health Research Fund (FIS), PI13/00061
to Granada, PI13/01162 to EPIC-Murcia, Regional Governments of Andalucía,
Asturias, Basque Country, Murcia, and Navarra, and ISCIII RETIC (RD06/0020)
(Spain); the Swedish Cancer Society, Swedish Research Council, and County
Councils of Skåne and Västerbotten (Sweden); and Cancer Research UK (14136 to
EPIC-Norfolk; C570/A16491 and C8221/A19170 to EPIC-Oxford), and the Medical
Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (UK).},
publisher = {Biomed Central},
keywords = {Breast cancer},
keywords = {Osteoprotegerin},
keywords = {RANK axis},
keywords = {Hormone receptor},
keywords = {Estrogen receptor},
keywords = {Progesterone receptor},
title = {Osteoprotegerin and breast cancer risk by hormone receptor subtype: a nested case-control study in the EPIC cohort},
doi = {10.1186/s12916-017-0786-8},
author = {Fortner, Renee T. and Sánchez Pérez, María José},
}