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Title: Circulating RANKL and RANKL/OPG and Breast Cancer Risk by ER and PR Subtype: Results from the EPIC Cohort
Author: Sarink, Danja
Schock, Helena
Johnson, Theron
Overvad, Kim
Holm, Marianne
Tjønneland, Anne
Boutron-Ruault, Marie-Christine
His, Mathilde
Kvaskoff, Marina
Boeing, Heiner
Lagiou, Pagona
Papatesta, Eleni Maria
Trichopoulou, Antonia
Palli, Domenico
Pala, Valeria
Mattiello, Amalia
Tumino, Rosario
Sacerdote, Carlotta
Bueno de Mesquita, H. Bas
van Gils, Carla H.
Peeters, Petra H. M.
Weiderpass, Elisabete
Agudo, Antonio
Sánchez, María José
Chirlaque, María Dolores
Ardanaz, Eva
Amiano, Pilar
Khaw, Kay-Tee
Travis, Ruth C.
Dossus, Laure
Gunter, Marc J.
Rinaldi, Sabina
Merritt, Melissa A.
Riboli, Elio
Kaaks, Rudolf
Fortner, Renée T.
Keywords: Càncer de mama
Receptors d'hormones
Breast cancer
Hormone receptors
Issue Date: 1-Sep-2017
Publisher: American Association for Cancer Research
Abstract: Receptor 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.
Note: Versió postprint del document publicat a:
It is part of: Cancer Prevention Research, 2017, vol. 10, num. 9, p. 525-534
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Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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