Colon cancer and vitamin D

Vitamin D is an important prohormone for calcium homeostasis and for optimal bone health. Since this vitamin is made in the skin after exposure to sunlight, it was assumed that deficiency of this vitamin was rare among healthy adults. However, due to increasing concern for skin cancer and decreasing intake of vitamin D containing foods such as milk, many young adults are at risk for vitamin D deficiency. The initial aim of this thesis was to determine the prevalence of vitamin D deficiency among a young healthy population. It was determined that nearly one third of young healthy adults suffered from vitamin D deficiency and secondary hyperparathyroidism. Since vitamin D deficiency has been implicated as a possible risk factor for many common cancers including colon cancer, a study was conducted to determine the prevalence of vitamin D deficiency among patients with cancer. Nearly 50% of patients with cancer suffered from vitamin D deficiency compared to only 12% of age matched controls. A series of in vitro and in vivo experiments were designed to test the hypothesis that vitamin D is protective against colon cancer cell proliferation. Using 3H-thymidine incorporation into DNA as a marker of proliferation, it was determined that human and mouse colon cancer growth was inhibited in the presence of the active form of vitamin D, 1,25-dihydroxyvitamin D 3. Using the MC-26/Balb/c colon cancer model, it was demonstrated that vitamin D deficient mice had 40% larger tumors than vitamin D sufficient mice. Additional experiments revealed that treatment with 1,25(OH)2D 3 and a Gemini-19-nor-vitamin D analogue decreased the metastatic colon cancer progression in mice. The possibility that colon cancer tumors have the ability to convert circulating 25-hydroxyvitamin D to active anti-proliferative metabolite of vitamin D3, 1,25(OH)2D3, was evaluated. The expression of mRNA for the 25-hydroxyvitamin D-1-alpha-hydroxylase was detected in human colon cancer specimens and several human colon cancer cell lines. Western blot analysis confirmed the protein expression of the 1-alpha-hydroxylase in the colon tissues. In conclusion, this translational research project defines vitamin D deficiency as an important unrecognized health problem and provides evidence that vitamin D may protect or inhibit the progression of one of the most common human cancers, namely colon cancer.