Vitamin D and colorectal cancer: molecular, epidemiological and clinical evidence

Abstract

In many cells throughout the body, vitamin D is converted into its active form calcitriol, and binds to vitamin D receptor (VDR), which functions as a transcription factor to regulate various biological processes including cellular differentiation and immune response. Vitamin D metabolizing enzymes (including CYP24A1 and CYP27B1) and VDR play major roles in exerting and regulating effects of vitamin D. Preclinical and epidemiological studies provide evidence for anticancer effects of vitamin D (in particular, against colorectal cancer), though clinical trials have yet to prove its benefit. Additionally, molecular pathological epidemiology research can provide insights into the interaction of vitamin D with tumour molecular and immunity status. Other future research directions include genome-wide research on VDR transcriptional targets, gene-environment interaction analyses, and clinical trials on vitamin D efficacy in colorectal cancer patients. Here we review the literature on vitamin D and colorectal cancer from both mechanistic and population studies, and discuss the links and controversies within and between the two parts of evidence.

In vitro and clinical data analysis of Osteopontin as a prognostic indicator in colorectal cancer

“…Some reports indicated that calcitriol would enhance radiation sensitivity in colorectal cancer regulated by the epithelial‐mesenchymal transition, for example, in vitro experiment trial of DLD1 and HCT116, 24 hours calcitriol pre‐treatment enhanced the radiation sensitivity by 2.3‐ and 2.6‐fold . Pre‐clinical and epidemiological studies have promoted the anti‐tumour effect of calcitriol, particularly against colorectal cancer which involved in anti‐proliferation, pro‐differentiation, pro‐apoptosis, anti‐angiogenesis, immune modulation and miR regulation . A number of genes are recognized to contain functional vitamin D response elements, which also include OPN .…”

Colonic transcriptional response to 1α,25(OH) 2 vitamin D 3 in African- and European-Americans

“…Multiple lines of evidence show that vitamin D has protective actions against malignant transformation (9, 11–13, 46) and epidemiological studies correlated serum vitamin D with CRC risk (4–6). However, it is not known how individuals differ in their tissue-specific responses to a fixed dose of 1α,25(OH) 2 D 3 , which, in turn, could impact disease risk irrespective of differences in serum 25(OH)D levels.…”

“…Transcriptome-wide studies have identified thousands of differentially expressed (DE) genes of which many are primary targets of the VDR and show cell type-specificity (7, 8). 1α,25(OH) 2 D 3 is thought to exert its chemoprotective effects in the colon through inhibition of proliferation and induction of differentiation and apoptosis (9–13), although additional mechanisms are likely and remain understudied. Inactive 25-hydroxyvitamin D (25(OH)D), which is measured in the serum, is converted to 1α,25(OH) 2 D 3 locally in the colonic epithelium (7, 8), and also likely contributes to anti-tumor effects.…”

Vitamin D/VDR, Probiotics, and Gastrointestinal Diseases

“…It seems like that the effects of both probiotics and vitamin D/VDR in colorectal cancer patients are not conclusive, e.g. as recently reviewed by Dou et al [71] , epidemiological studies have consistently demonstrated a strong inverse association of plasma 25(OH)D concentration with colorectal cancer incidence and mortality. However, the effect of vitamin D intake on colorectal cancer prevention is controversial [72–74] .…”