Title |
Osteoprotegerin and breast cancer risk by hormone receptor subtype: a nested case-control study in the EPIC cohort
|
---|---|
Published in |
BMC Medicine, February 2017
|
DOI | 10.1186/s12916-017-0786-8 |
Pubmed ID | |
Authors |
Renée T. Fortner, Danja Sarink, Helena Schock, Theron Johnson, Anne Tjønneland, Anja Olsen, Kim Overvad, Aurélie Affret, Mathilde His, Marie-Christine Boutron-Ruault, Heiner Boeing, Antonia Trichopoulou, Androniki Naska, Philippos Orfanos, Domenico Palli, Sabina Sieri, Amalia Mattiello, Rosario Tumino, Fulvio Ricceri, H. Bas Bueno-de-Mesquita, Petra H. M. Peeters, Carla H. Van Gils, Elisabete Weiderpass, Eiliv Lund, J. Ramón Quirós, Antonio Agudo, Maria-José Sánchez, María-Dolores Chirlaque, Eva Ardanaz, Miren Dorronsoro, Tim Key, Kay-Tee Khaw, Sabina Rinaldi, Laure Dossus, Marc Gunter, Melissa A. Merritt, Elio Riboli, Rudolf Kaaks |
Abstract |
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. 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. 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). 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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
Spain | 4 | 80% |
United Kingdom | 1 | 20% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 4 | 80% |
Practitioners (doctors, other healthcare professionals) | 1 | 20% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 53 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 9 | 17% |
Student > Master | 8 | 15% |
Student > Ph. D. Student | 5 | 9% |
Student > Doctoral Student | 4 | 8% |
Professor > Associate Professor | 4 | 8% |
Other | 9 | 17% |
Unknown | 14 | 26% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 15 | 28% |
Biochemistry, Genetics and Molecular Biology | 5 | 9% |
Agricultural and Biological Sciences | 5 | 9% |
Nursing and Health Professions | 2 | 4% |
Environmental Science | 1 | 2% |
Other | 6 | 11% |
Unknown | 19 | 36% |