Vitamin D axis and its role in skin carcinogenesis: a comprehensive review

Vitamin D (VD) is a secosteroid hormone that is mainly synthesized in the skin upon exposure to UVB radiation. VD is widely known for its role in calcium metabolism; however, multiple endocrine, paracrine and autocrine functions of VD have been described, including a prominent role on carcinogenesis. In recent years, multiple associations between VD deficiency and different types of cancer have been described, supported by evidence of anti-proliferative, anti-angiogenic, pro-apoptotic, cell-differentiating and anti-invasive effects of this hormone. An immunomodulatory role of VD associated to cancer microenvironment has also been suggested. Regarding skin cancer, it has been shown that VD inhibits tumor development in basal cell carcinoma, squamous cell carcinoma, and melanoma in vitro. Some studies have suggested that lower VD levels may be a risk factor for skin cancer, while others have shown the opposite; there is also preliminary evidence on the role of VD supplementation for the prevention of melanoma in vivo. In this review, we explore the mechanisms of VD effects on carcinogenesis and the available scientific evidence of the interplay between VD and the genesis of both non-melanoma and melanoma skin cancer.