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

• Published in: BMC medicine 2017-02, Vol.15 (1), p.26, Article 26
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Apoptosis; Blood & organ donations; Breast cancer; Breast Neoplasms - blood; Case-Control Studies; Cohort Studies; Community medicine, Social medicine: 801; Cytokine receptors; Estrogen; Female; Health aspects; Health sciences: 800; Helsefag: 800; Humans; Laboratories; Ligands; Medical disciplines: 700; Medical research; Medicin och hälsovetenskap; Medisinske Fag: 700; Melanoma; Metastasis; Middle Aged; Mortality; Osteoprotegerin - blood; Physiological aspects; Prospective Studies; Receptors; Reproducibility; Risk Factors; Samfunnsmedisin, sosialmedisin: 801; Skin cancer; Tumor necrosis factor-TNF; VDP; Womens health
• ISSN: 1741-7015; 1741-7015
• DOI: 10.1186/s12916-017-0786-8

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. 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. 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  = 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  = 0.97), and we observed no heterogeneity by HT use at blood collection (p  ≥ 0.43) or age at breast cancer diagnosis (p  ≥ 0.30). 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.