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

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). Circulati...

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Detalles Bibliográficos
Autores principales: Fortner, Renée T., Sarink, Danja, Schock, Helena, Johnson, Theron, Tjønneland, Anne, Olsen, Anja, Overvad, Kim, Affret, Aurélie, His, Mathilde, Boutron-Ruault, Marie-Christine, Boeing, Heiner, Trichopoulou, Antonia, Naska, Androniki, Orfanos, Philippos, Palli, Domenico, Sieri, Sabina, Mattiello, Amalia, Tumino, Rosario, Ricceri, Fulvio, Bueno-de-Mesquita, H. Bas, Peeters, Petra H. M., Van Gils, Carla H., Weiderpass, Elisabete, Lund, Eiliv, Quirós, J. Ramón, Agudo, Antonio, Sánchez, Maria-José, Chirlaque, María-Dolores, Ardanaz, Eva, Dorronsoro, Miren, Key, Tim, Khaw, Kay-Tee, Rinaldi, Sabina, Dossus, Laure, Gunter, Marc, Merritt, Melissa A., Riboli, Elio, Kaaks, Rudolf
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Research Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5297136/
https://www.ncbi.nlm.nih.gov/pubmed/28173834
http://dx.doi.org/10.1186/s12916-017-0786-8
Descripción
Sumario: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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12916-017-0786-8) contains supplementary material, which is available to authorized users.

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