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Cancers 2014, 6(1), 211-225; doi:10.3390/cancers6010211

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

1
Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY 14263, USA
2
Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, NY 14263, USA
3
Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY 14263, USA
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 25 November 2013 / Revised: 23 December 2013 / Accepted: 9 January 2014 / Published: 27 January 2014
(This article belongs to the Special Issue Vitamin D: Role in Cancer Causation, Progression and Therapy)
View Full-Text   |   Download PDF [539 KB, 29 January 2014; original version 27 January 2014]

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. View Full-Text
Keywords: interactions; 25-hydroxyvitamin D; cytokines; breast cancer; epidemiology; biomarker interactions; 25-hydroxyvitamin D; cytokines; breast cancer; epidemiology; biomarker
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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MDPI and ACS Style

Yao, S.; Hong, C.-C.; McCann, S.E.; Zirpoli, G.; Quan, L.; Gong, Z.; Johnson, C.S.; Trump, D.L.; Ambrosone, C.B. Combined Effects of Circulating Levels of 25-Hydroxyvitamin D and Th1 and Th2 Cytokines on Breast Cancer Estrogen Receptor Status. Cancers 2014, 6, 211-225.

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