Osteoprotegerin and breast cancer risk by hormone receptor subtype: a nested case-control study in the EPIC cohort. Issue 1 (December 2017)

• Record Type: Journal Article
• Authors: Fortner, Renée; 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.; Peeters, Petra; Van Gils, Carla; Weiderpass, Elisabete; Lund, Eiliv; Quirós, J.; 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; Riboli, Elio; Kaaks, Rudolf;
• Is Part Of: BMC medicine. Volume 15:Issue 1(2017)
• Page Start: 1
• Page End: 10
• Publication Date: 2017-12
• Subjects: Breast cancer -- Osteoprotegerin -- RANK axis -- Hormone receptor -- Estrogen receptor -- Progesterone receptor; Medicine -- Periodicals; 610.5
• DOI: 10.1186/s12916-017-0786-8
• Languages: English
• ISSNs: 1741-7015

Abstract

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.