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Osteoprotegerin and breast cancer risk by hormone receptor subtype: a nested case-control study in the EPIC cohort.
- Source :
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BMC medicine [BMC Med] 2017 Feb 08; Vol. 15 (1), pp. 26. Date of Electronic Publication: 2017 Feb 08. - Publication Year :
- 2017
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Abstract
- Background: Circulating osteoprotegerin (OPG), a member of the receptor activator of nuclear factor kappa-B (RANK) axis, may influence breast cancer risk via its role as the decoy receptor for both the RANK ligand (RANKL) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Circulating OPG and breast cancer risk has been examined in only one prior study.<br />Methods: A case-control study was nested in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. A total of 2008 incident invasive breast cancer cases (estrogen receptor (ER)+, n = 1622; ER-, n = 386), matched 1:1 to controls, were included in the analysis. Women were predominantly postmenopausal at blood collection (77%); postmenopausal women included users and non-users of postmenopausal hormone therapy (HT). Serum OPG was quantified with an electrochemiluminescence assay. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression.<br />Results: The associations between OPG and ER+ and ER- breast cancer differed significantly. Higher concentrations of OPG were associated with increased risk of ER- breast cancer (top vs. bottom tertile RR = 1.93 [95% CI 1.24-3.02]; p <subscript>trend</subscript> = 0.03). We observed a suggestive inverse association for ER+ disease overall and among women premenopausal at blood collection. Results for ER- disease did not differ by menopausal status at blood collection (p <subscript>het</subscript> = 0.97), and we observed no heterogeneity by HT use at blood collection (p <subscript>het</subscript> ≥ 0.43) or age at breast cancer diagnosis (p <subscript>het</subscript> ≥ 0.30).<br />Conclusions: This study provides the first prospective data on OPG and breast cancer risk by hormone receptor subtype. High circulating OPG may represent a novel risk factor for ER- breast cancer.
Details
- Language :
- English
- ISSN :
- 1741-7015
- Volume :
- 15
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- BMC medicine
- Publication Type :
- Academic Journal
- Accession number :
- 28173834
- Full Text :
- https://doi.org/10.1186/s12916-017-0786-8