Sarink, DanjaSchock, HelenaJohnson, TheronOvervad, KimHolm, MarianneTjønneland, AnneBoutron-Ruault, Marie-ChristineHis, MathildeKvaskoff, MarinaBoeing, HeinerLagiou, PagonaPapatesta, Eleni MariaTrichopoulou, AntoniaPalli, DomenicoPala, ValeriaMattiello, AmaliaTumino, RosarioSacerdote, CarlottaBueno de Mesquita, H. Basvan Gils, Carla H.Peeters, Petra H. M.Weiderpass, ElisabeteAgudo, AntonioSánchez, María JoséChirlaque, María DoloresArdanaz, EvaAmiano, PilarKhaw, Kay-TeeTravis, Ruth C.Dossus, LaureGunter, Marc J.Rinaldi, SabinaMerritt, Melissa A.Riboli, ElioKaaks, RudolfFortner, Renée T.2018-09-052018-09-052017-09-01https://hdl.handle.net/2445/124271Receptor activator of nuclear factor-kappa B (RANK)-RANK ligand (RANKL) signaling promotes mammary tumor development in experimental models. Circulating concentrations of soluble RANKL (sRANKL) may influence breast cancer risk via activation of RANK signaling; this may be modulated by osteoprotegerin (OPG), the decoy receptor for RANKL. sRANKL and breast cancer risk by hormone receptor subtype has not previously been investigated. A case-control study was nested in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. This study included 1,976 incident invasive breast cancer cases [estrogen receptor positive (ER+), n = 1,598], matched 1: 1 to controls. Women were pre- or postmenopausal at blood collection. Serum sRANKL was quantified using an ELISA, serum OPG using an electrochemiluminescent assay. Risk ratios (RR) and 95% confidence intervals (95% CI) were calculated using conditional logistic regression. Associations between sRANKL and breast cancer risk differed by tumor hormone receptor status (P-het = 0.05). Higher concentrations of sRANKL were positively associated with risk of ER+ breast cancer [5th vs. 1st quintile RR 1.28 (95% CI, 1.01-1.63); P-trend = 0.20], but not ER+ disease. For both ER+ and estrogen and progesterone receptor positive (ER+PR+) breast cancer, results considering the sRANKL/OPG ratio were similar to those for sRANKL; we observed a suggestive inverse association between the ratio and ER+PR+ disease [5th vs. 1st quintile RR = 0.60 (0.31-1.14); P-trend = 0.03]. This study provides the first large-scale prospective data on circulating sRANKL and breast cancer. We observed limited evidence for an association between sRANKL and breast cancer risk.20 p.application/pdfeng(c) American Association for Cancer Research, 2017Càncer de mamaReceptors d'hormonesBreast cancerHormone receptorsinfo:eu-repo/semantics/article2018-07-24info:eu-repo/semantics/openAccess28701332