Mounting evidence suggests a biological plausibility for anti-carcinogenic effects of vitamin D, which could explain these results. 1,25(OH)2D, which has been shown to be produced locally by various cancer cells metabolizing the substrate 25(OH)D [38], inhibits carcinogenesis by several mechanisms [141]. 1,25(OH)2D exerts anti-proliferative effects on cancer cells by promoting cyclin-dependent kinase (CDK) inhibitor synthesis, and by influencing several growth factors and their signaling pathways including insulin-like growth factor 1 (IGF-1), transforming growth factor β (TGFβ), Wnt/β-catenin, MAP kinase 5 (MAPK5) and nuclear factor κB (NF-kB) [142] (Figure 5).