Publication: Osteoprotegerin and breast cancer risk by hormone receptor subtype: a nested case-control study in the EPIC cohort
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Identifiers
Date
2017-02-08
Authors
Fortner, Renée T
Sarink, Danja
Schock, Helena
Johnson, Theron
Tjønneland, Anne
Olsen, Anja
Overvad, Kim
Affret, Aurélie
His, Mathilde
Boutron-Ruault, Marie-Christine
Advisors
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Journal ISSN
Volume Title
Publisher
BioMed Central
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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.
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.
Description
MeSH Terms
Medical Subject Headings::Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::DNA-Binding Proteins::Receptors, Cytoplasmic and Nuclear::Receptors, Steroid::Receptors, Estrogen
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, Immunologic::Receptors, Cytokine::Receptors, Tumor Necrosis Factor::Tumor Necrosis Factor Decoy Receptors::Osteoprotegerin
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Transcription Factors::Receptors, Cytoplasmic and Nuclear::Receptors, Steroid::Receptors, Progesterone
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, Immunologic::Receptors, Cytokine::Receptors, Tumor Necrosis Factor::Receptor Activator of Nuclear Factor-kappa B
Medical Subject Headings::Health Care::Environment and Public Health::Public Health::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies
Medical Subject Headings::Health Care::Environment and Public Health::Public Health::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Prospective Studies
Medical Subject Headings::Phenomena and Processes::Reproductive and Urinary Physiological Phenomena::Reproductive Physiological Phenomena::Climacteric::Menopause::Postmenopause
Medical Subject Headings::Health Care::Environment and Public Health::Public Health::Epidemiologic Factors::Causality::Risk Factors
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::DNA-Binding Proteins::Receptors, Cytoplasmic and Nuclear::Receptors, Steroid::Receptors, Estrogen
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, Immunologic::Receptors, Cytokine::Receptors, Tumor Necrosis Factor::Tumor Necrosis Factor Decoy Receptors::Osteoprotegerin
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Transcription Factors::Receptors, Cytoplasmic and Nuclear::Receptors, Steroid::Receptors, Progesterone
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, Immunologic::Receptors, Cytokine::Receptors, Tumor Necrosis Factor::Receptor Activator of Nuclear Factor-kappa B
Medical Subject Headings::Health Care::Environment and Public Health::Public Health::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies
Medical Subject Headings::Health Care::Environment and Public Health::Public Health::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Prospective Studies
Medical Subject Headings::Phenomena and Processes::Reproductive and Urinary Physiological Phenomena::Reproductive Physiological Phenomena::Climacteric::Menopause::Postmenopause
Medical Subject Headings::Health Care::Environment and Public Health::Public Health::Epidemiologic Factors::Causality::Risk Factors
DeCS Terms
CIE Terms
Keywords
Breast cancer, Neoplasias de la mama, Estrogen receptor, Hormone receptor, Osteoprotegerin, Osteoprotegerina, Progesterone receptor, Receptores de progesterona, Receptores estrogénicos, Receptores de hormonas, RANK axis
Citation
Fortner R, Sarink D, Schock H, Johnson T, Tjønneland A, Olsen A et al. Osteoprotegerin and breast cancer risk by hormone receptor subtype: a nested case-control study in the EPIC cohort. BMC Medicine. 2017;15(1)