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. 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. 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 trend = 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 het = 0.97), and we observed no heterogeneity by HT use at blood collection (p het ≥ 0.43) or age at breast cancer diagnosis (p het ≥ 0.30). 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.

Osteoprotegerin and breast cancer risk by hormone receptor subtype: A nested case-control study in the EPIC cohort

Ricceri F.;
2017

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. 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. 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 trend = 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 het = 0.97), and we observed no heterogeneity by HT use at blood collection (p het ≥ 0.43) or age at breast cancer diagnosis (p het ≥ 0.30). 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.
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Breast cancer; Estrogen receptor; Hormone receptor; Osteoprotegerin; Progesterone receptor; RANK axis; Breast Neoplasms; Case-Control Studies; Cohort Studies; Female; Humans; Middle Aged; Osteoprotegerin; Prospective Studies; Risk Factors
Fortner R.T.; Sarink D.; Schock H.; Johnson T.; Tjonneland A.; Olsen A.; Overvad K.; Affret A.; His M.; Boutron-Ruault M.-C.; Boeing H.; Trichopoulou A.; Naska A.; Orfanos P.; Palli D.; Sieri S.; Mattiello A.; Tumino R.; Ricceri F.; Bueno-de-Mesquita H.B.; Peeters P.H.M.; Van Gils C.H.; Weiderpass E.; Lund E.; Quiros J.R.; Agudo A.; Sanchez M.-J.; Chirlaque M.-D.; Ardanaz E.; Dorronsoro M.; Key T.; Khaw K.-T.; Rinaldi S.; Dossus L.; Gunter M.; Merritt M.A.; Riboli E.; Kaaks R.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2318/1766520
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