Fortner, Renée T.Sarink, DanjaSchock, HelenaJohnson, TheronTjønneland, AnneOlsen, AnjaOvervad, KimAffret, AurélieHis, MathildeBoutron-Ruault, Marie-ChristineBoeing, HeinerTrichopoulou, AntoniaNaska, AndronikiOrfanos, PhilipposPalli, DomenicoSieri, SabinaMattiello, AmaliaTumino, RosarioRicceri, FulvioBueno de Mesquita, H. BasPeeters, Petra H. M.van Gils, Carla H.Weiderpass, ElisabeteLund, EilivQuirós, José RamónAgudo, AntonioSánchez, María JoséChirlaque, María DoloresArdanaz, EvaDorronsoro, MirenKey, Timothy J.Khaw, Kay-TeeRinaldi, SabinaDossus, LaureGunter, Marc J.Merritt, Melissa A.Riboli, ElioKaaks, Rudolf2018-09-062018-09-062017-02-08https://hdl.handle.net/2445/124324Background: 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.10 p.application/pdfengcc by (c) Fortner et al., 2017http://creativecommons.org/licenses/by/3.0/es/Càncer de mamaNecrosiBreast cancerNecrosisinfo:eu-repo/semantics/article2018-07-24info:eu-repo/semantics/openAccess28173834