Combined Effects of Circulating Levels of 25-Hydroxyvitamin D and Th1 and Th2 Cytokines on Breast Cancer Estrogen Receptor Status

Song Yao,Chi-Chen Hong,Zhihong Gong,Susan Mccann,Candace Johnson,Gary Zirpoli,Christine Ambrosone,Donald Trump,Lei Quan

doi:10.3390/cancers6010211

Song Yao, Chi-Chen Hong + Show 7 more

Open Access

https://doi.org/10.3390/cancers6010211

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Journal: Cancers	Publication Date: Jan 27, 2014
Citations: 3	License type: CC BY 4.0

Affiliation: Roswell Park Cancer Institute

Abstract

Vitamin D has been recognized for its immune-modulating properties. We have previously found that levels of 25OHD, and cytokines including IL5, IFNα2, and TNFα, are also associated with estrogen receptor (ER) negative breast cancer in younger women. Thus, we hypothesized that there may be interactions between vitamin D and the immune system in influencing breast cancer ER status, which was tested in 490 women with incident breast cancer. There was no correlation of the levels of 25OHD with any cytokine, and their associations with tumor ER negative status were independent of each other. However, premenopausal women with low 25OHD and high TNFα levels had the highest likelihood of having ER negative cancer (odds ratio [OR] = 7.32, 95% confidence interval [CI] = 2.44−21.98), with evidence of synergy between the two (relative excess risk due to interaction [RERI] = 5.46, p for additive interaction = 0.14, and p for multiplicative interaction = 0.09). There were similar synergistic associations between 25OHD and IL5, and several IFNα2 to Th2 cytokine ratios. This is the first study to provide evidence of interactions between vitamin D and the immune system in relation to breast cancer ER status, which may inform combinational use of vitamin D and anti-inflammatory drugs for cancer prevention and therapy.

Highlights

There is a rich body of evidence supporting vitamin D as a potent immunomodulator [1,2,3,4]
We examined the combinational associations of serum levels of 25OHD with plasma levels of three cytokines, interferon α2 (IFNα2), tumor necrosis factor α (TNFα) and interleukin 5 (IL5), as well as ten cytokine ratios, on estrogen receptor (ER) status of breast cancer
There was some evidence for antagonistic associations between 25OHD and IFNα2 on ER status, which was found for two cytokine ratios where IFNα2 was the numerator

Summary

Introduction

There is a rich body of evidence supporting vitamin D as a potent immunomodulator [1,2,3,4]. VDR and vitamin D activating enzyme 1α-hydroxylase is expressed in almost all immune cells [5]. While enhancing innate immune responses against bacterial infection, vitamin D modulates adaptive immunity by influencing the actions of antigen presenting cells (APCs) and T-helper lymphocytes. Among the genes upregulated by vitamin D stimulation, it was found that genes involved in autoimmune diseases are enriched [7]. In randomized clinical trials of patients with cardiovascular disease and colorectal adenoma, vitamin D supplementation significantly alters patients’ immune profiles [8,9]

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Conclusion