THE ROLE OF VITAMIN D AND VDR IN CARCINOGENESIS: THROUGH EPIDEMIOLOGY AND BASIC SCIENCES
Abstract
In the last two decades
vitamin D (VD) research has demonstrated new extraskeletal actions of
this pre-hormone, suggesting a protective role of this secosteroid in
the onset, progression and prognosis of several chronic noncommunicable
diseases, such as cardiovascular disease, diabetes mellitus or
cancer.
Regarding carcinogenesis, both preclinical and epidemiological evidence
available show oncoprotective actions of VD and its receptor, the VDR.
However, in late neoplastic stages the VD system (VDS)
seems to be less
functional, which appears to be due to an epigenetic silencing of the
system. In
preclinical experimental studies, VD presents oncoprotective
actions through modulation of inflammation, cell proliferation, cell
differentiation, angiogenesis, invasive and metastatic potential,
apoptosis, miRNA expression regulation and modulation of the Hedgehog
signalling pathway.
Moreover, epidemiological evidence points towards an
oncoprotective role of vitamin D and VDR in colorectal cancer. This
association is more controversial with breast, ovarian and prostate
cancers, although with a few adverse effects. Nonetheless, we should
consider other factors to determine the benefit of increased serum
concentration of VD.
Much of the epidemiological evidence is still
inconclusive, and we will have to wait for new, better-designed ongoing
RCTs and their results to discern the real effect of vitamin D in cancer
risk reduction and therapy. The objective of this literature review is
to offer an up-to-date analysis of the role of the VD and VDR, in the
onset, progression and prognosis of all types of cancer. We further
discuss the available literature and suggest new hypotheses and future
challenges in the field of VD research.
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