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Circulating RANKL and RANKL/OPG and Breast Cancer Risk by ER and PR Subtype: Results from the EPIC Cohort.
- Source :
-
Cancer prevention research (Philadelphia, Pa.) [Cancer Prev Res (Phila)] 2017 Sep; Vol. 10 (9), pp. 525-534. Date of Electronic Publication: 2017 Jul 12. - Publication Year :
- 2017
-
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 <subscript>het</subscript> = 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 <subscript>trend</subscript> = 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 <subscript>trend</subscript> = 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 .<br /> (©2017 American Association for Cancer Research.)
- Subjects :
- Adult
Aged
Breast pathology
Breast Neoplasms pathology
Case-Control Studies
Female
Follow-Up Studies
Humans
Incidence
Middle Aged
Prospective Studies
Receptors, Estrogen metabolism
Receptors, Progesterone metabolism
Risk Factors
Breast Neoplasms blood
Breast Neoplasms epidemiology
Osteoprotegerin blood
RANK Ligand blood
Subjects
Details
- Language :
- English
- ISSN :
- 1940-6215
- Volume :
- 10
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Cancer prevention research (Philadelphia, Pa.)
- Publication Type :
- Academic Journal
- Accession number :
- 28701332
- Full Text :
- https://doi.org/10.1158/1940-6207.CAPR-17-0125