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    Circulating RANKL and RANKL/OPG and Breast Cancer Risk by ER and PR Subtype: Results from the EPIC Cohort.

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    Authors
    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 B As
    van Gils, Carla H
    Peeters, Petra H
    Weiderpass, Elisabete
    Agudo, Antonio
    Sánchez, Maria-José
    Chirlaque, Maria-Dolores
    Ardanaz, Eva
    Amiano, Pilar
    Khaw, Kay Tee
    Travis, Ruth
    Dossus, Laure
    Gunter, Mark
    Rinaldi, Sabina
    Merritt, Melissa
    Riboli, Elio
    Kaaks, Rudolf
    Fortner, Renée T
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    Type
    Article
    Language
    en
    
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    Title
    Circulating RANKL and RANKL/OPG and Breast Cancer Risk by ER and PR Subtype: Results from the EPIC Cohort.
    Published in
    Cancer Prev Res 2017; 10(9):525-34
    Publiekssamenvatting
    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 (Phet= 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);Ptrend= 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);Ptrend= 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.Cancer Prev Res; 10(9); 525-34. ©2017 AACR.
    DOI
    10.1158/1940-6207.CAPR-17-0125
    PMID
    28701332
    URI
    http://hdl.handle.net/10029/621554
    ae974a485f413a2113503eed53cd6c53
    10.1158/1940-6207.CAPR-17-0125
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