Vitamin D Influence on Cancer Risk and Progression
Summary
Vitamin D, obtained through cutaneous synthesis and dietary sources, is metabolised into its active form, calcitriol, which exerts genomic and non-genomic effects via the vitamin D receptor (VDR). A substantial body of epidemiological evidence links low circulating 25-hydroxyvitamin D levels with increased incidence and poorer outcomes in multiple malignancies, including colorectal, breast and prostate tumours. Mechanistic investigations have revealed that vitamin D signalling regulates key hallmarks of cancer by controlling cell proliferation, differentiation, apoptosis and angiogenesis, as well as modulating inflammatory and immune responses within the tumour microenvironment. Dysregulation of vitamin D metabolic enzymes and VDR expression is frequently observed in neoplastic tissues, contributing to resistance against the hormone’s antitumourigenic actions. Randomised trials of supplementation have yielded mixed results, highlighting the complexity of dose–response relationships and the influence of genetic, environmental and lifestyle factors. Globally, optimising vitamin D status offers a practical avenue for cancer prevention, while emerging strategies aim to harness VDR-targeted therapies and combination regimens to improve progression-free survival and treatment efficacy.
Research from Nature Portfolio
Recent meta-analytical work encompassing cohort and case-control designs has demonstrated a consistent inverse association between serum 25-hydroxyvitamin D concentrations and breast cancer risk in premenopausal women, with a protective effect plateauing beyond defined thresholds. Notably, no significant associations were observed for dietary vitamin D intake or circulating levels of the active metabolite, emphasising the primacy of 25-hydroxyvitamin D as a biomarker for risk stratification. This refined understanding of menopausal status and dose–response kinetics informs targeted screening and supplementation guidelines.
Vitamin D Influence on Cancer Risk and Progression publication trend
The graph below shows the total number of articles in vitamin d influence on cancer risk and progression across all publications each year (not limited to Nature Index journals).
Technical terms
25-hydroxyvitamin D (25(OH)D): The principal circulating form of vitamin D, used as an indicator of vitamin D status.
Calcitriol (1,25-dihydroxyvitamin D3): The hormonally active metabolite of vitamin D that binds to VDR to regulate gene expression.
Vitamin D receptor (VDR): A nuclear receptor that mediates the genomic effects of calcitriol.
Chemokine CCL20: A cytokine implicated in recruitment and polarisation of immune cells, notably M2 macrophages.
M2 macrophage: An alternatively activated macrophage phenotype associated with tissue repair and tumour-promoting functions.
References
- VDR promotes pancreatic cancer progression in vivo by activating CCL20-mediated M2 polarization of tumor associated macrophage. Cell Communication and Signaling (2024).
- Exploring vitamin D metabolism and function in cancer. Experimental & Molecular Medicine (2018).
- Vitamin D and Cancer: An Historical Overview of the Epidemiology and Mechanisms. Nutrients (2022).
- Vitamin D exposure and Risk of Breast Cancer: a meta-analysis. Scientific Reports (2018).
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