Vitamin D, Cancer Risk, and Mortality.

Antiproliferative effects of 1,25-dihydroxyvitamin D, the biologically active form of vitamin D, are well established in various cell types by influencing cell differentiation and decreasing cell proliferation, growth, invasion, angiogenesis, and metastasis. Several meta-analyses showed that low serum levels of 25(OH)D was associated with colorectal cancer and overall mortality, while the association with cancer mortality was less consistent. VDR is a crucial mediator for the cellular effects of vitamin D and conflicting data have been reported for most malignancies. Beyond VDR, the biological effects of vitamin D are mediated by the vitamin D-binding protein. The GC (group-specific component) gene, encoding DBP, is highly polymorphic and several polymorphisms were investigated in association with cancer development with controversial results. Vitamin D supplementation was found to be associated with a reduced risk of overall mortality, reviewing all published trials on healthy subjects, whereas the evidence of an effect on cancer risk and mortality is less clear. Furthermore, long-term health effects of high doses of vitamin D, extended duration of supplementation, and the association with different baseline vitamin D levels remain to be investigated. In summary, epidemiological and preclinical studies support the development of vitamin D as preventative and therapeutic anticancer agents, with significant associations especially found for low vitamin D status with overall mortality and cancer outcome, more than cancer incidence. However, a definitive conclusion cannot be drawn and only large randomized clinical trials, both in healthy subjects and in cancer patients, will allow to draw definitive conclusions on the effect of vitamin D supplementation on cancer risk, prognosis, and mortality.