Sunlight, the vitamin D endocrine system, and their relationships with gynaecologic cancer.

Vitamin D has classically been considered an important nutrient, but modern scientific evidence points out that it has a new and more critical role as ubiquitous hormone at the centre of a complex endocrine, paracrine, and autocrine system involved in maintaining general health. Vitamin D is found in small quantities in food; however, it is also produced by the skin when exposed to certain intensities of ultraviolet light. Substantial epidemiological and clinical data suggest a link between low levels of vitamin D and an increased risk of a number of female specific cancers. Different types of cancer cells present vitamin D receptors and the enzymatic system involved in both vitamin D synthesis and inhibition. Sustained low levels of its precursor are responsible for alterations in vitamin D tissue and cell production and metabolism. The active form of vitamin D, 1,25(OH)2D3, can induce differentiation, inhibit proliferation, and modulate immune responsiveness of breast and a wide variety of female genital cell types. Vitamin D effects have been observed on expression of cell cycle regulators, growth factors and their receptors, apoptotic machinery, metastatic potential, and angiogenesis; all of which have some effect on hyperproliferative conditions. However, vitamin D blood levels may not be representative of the local metabolic alterations during carcinogenesis. Clinical studies support the recommendation to increase vitamin D levels to a normal range in order to prevent the tissue disorders related to hypovitaminosis D which are thought to be involved in the initiation and progression of cancer.