Abstract
Adipose tissue is involved in the etiology of postmenopausal breast cancer, possibly through increased sex steroid hormone production, inflammation, and altered adipokines. Vitamin D may affect these pathways but its effect on gene expression in different tissues has not been examined. Within a double-blind, 12-month placebo-controlled randomized trial, we compared 2000 IU/day oral vitamin D3 supplementation (N = 39) vs. placebo (N = 40) on the expression of 5 genes in breast and adipose tissue in overweight/obese postmenopausal women (50–75 years). All participants had serum 25-hydroxyvitamin D (25(OH)D) levels ≥ 10–<32 ng/mL (“insufficient”) and concurrently completed a behavioral weight loss program. Random periareolar fine needle aspiration (RPFNA) and abdominal subcutaneous adipose tissue biopsies were performed at baseline and 12 months. Changes in expression of aromatase (CYP19A1), peroxisome proliferator-activated receptor gamma (PPARG), adiponectin (ADIPOQ), monocyte-chemoattractant protein 1 (MCP-1), and vitamin D receptor (VDR) were analyzed by qRT-PCR. Compared to placebo, 2000 IU vitamin D did not show significant effects on gene expression in breast or adipose tissue. Replete women (i.e., 25(OH)D ≥ 32 ng/mL; N = 17) showed a small decrease in MCP-1 expression compared to an increase among women who remained ‘insufficient’ despite supplementation (N = 12) (Replete:−1.6% vs. Non-replete: 61.2%, p = 0.015) in breast, but not adipose tissue. No statistically significant differences in gene expression were detected according to degree of weight loss. Vitamin D repletion during weight loss may have different effects on gene expression in breast and adipose tissue. Further research on the localized effects of vitamin D is needed to determine its effect on breast cancer risk.
Highlights
Obesity is an established risk factor for postmenopausal breast cancer.[1]
vitamin D receptor (VDR) regulates metabolism[23] and calcitriol inhibits adipogenesis by acting on multiple targets including peroxisome proliferator-activated receptor gamma (PPARG) expression and modulating inflammation via reduced expression of inflammatory genes monocytechemoattractant protein 1 (MCP-1), IL-6, and IL-8.24 human studies of vitamin D and breast cancer risk are frequently limited to measuring peripheral blood biomarkers and few, if any, published data exist on the differential effects of vitamin D on gene expression in target tissues
In the context of a 12-month, double-blinded, placebocontrolled randomized trial, we investigated the effects of oral vitamin D3 supplementation (2000 IU/day) vs. placebo on the expression of 5 pre-selected genes in samples of breast random fine needle periaerolar fine needle aspirate (RPFNA) tissue and subcutaneous adipose tissue from a subset of postmenopausal women participating in a diet and exercise weight loss program
Summary
Obesity is an established risk factor for postmenopausal breast cancer.[1]. the mechanisms linking excess body weight and breast cancer risk are not fully understood, proposed mechanisms underlying this association include alterations in the production of sex steroid hormones, insulin resistance, adipose tissue dysfunction and altered cytokine levels that result in a state of chronic low grade inflammation.[2, 3]Vitamin D insufficiency, which is commonly observed with obesity,[4, 5] has been inversely associated,[6,7,8] not consistently,[9] with postmenopausal breast cancer risk in epidemiologic studies and clinical trials. Circulating vitamin D has been shown to have effects on several of the mechanistic pathways linking obesity and breast cancer risk, including leptin,[10] adiponectin,[11] insulin resistance,[12, 13] and markers of inflammation.[14, 15]. VDR regulates metabolism[23] and calcitriol inhibits adipogenesis by acting on multiple targets including PPARG expression and modulating inflammation via reduced expression of inflammatory genes MCP-1, IL-6, and IL-8.24 human studies of vitamin D and breast cancer risk are frequently limited to measuring peripheral blood biomarkers and few, if any, published data exist on the differential effects of vitamin D on gene expression in target tissues
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