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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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Title: Circulating RANKL and RANKL/OPG and Breast Cancer Risk by ER and PR Subtype: Results from the EPIC Cohort
Authors: Sarink, D
Schock, H
Johnson, T
Overvad, K
Holm, M
Tjonneland, A
Boutron-Ruault, M-C
His, M
Kvaskoff, M
Boeing, H
Lagiou, P
Papatesta, E-M
Trichopoulou, A
Palli, D
Pala, V
Mattiello, A
Tumino, R
Sacerdote, C
Bueno-de-Mesquita, HB
Van Gils, CH
Peeters, PH
Weiderpass, E
Agudo, A
Sanchez, M-J
Chirlaque, M-D
Ardanaz, E
Amiano, P
Khaw, KT
Travis, R
Dossus, L
Gunter, M
Rinaldi, S
Merritt, M
Riboli, E
Kaaks, R
Fortner, RT
Item Type: Journal Article
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 (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.
Issue Date: 12-Jul-2017
Date of Acceptance: 26-Jun-2017
URI: http://hdl.handle.net/10044/1/51652
DOI: https://dx.doi.org/10.1158/1940-6207.CAPR-17-0125
ISSN: 1940-6207
Publisher: American Association for Cancer Research
Start Page: 525
End Page: 534
Journal / Book Title: CANCER PREVENTION RESEARCH
Volume: 10
Issue: 9
Copyright Statement: © 2017 American Association for Cancer Research.
Keywords: Science & Technology
Life Sciences & Biomedicine
Oncology
KAPPA-B LIGAND
MAMMARY EPITHELIAL-CELLS
RECEPTOR ACTIVATOR
OSTEOPROTEGERIN OPG
BONE METASTASES
DOUBLE-BLIND
EXPRESSION
DIFFERENTIATION
PROLIFERATION
DISEASE
1103 Clinical Sciences
1112 Oncology And Carcinogenesis
Oncology & Carcinogenesis
Publication Status: Published
Appears in Collections:Faculty of Medicine
Epidemiology, Public Health and Primary Care



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