Molecular basis of the potential of vitamin D to prevent cancer.
OBJECTIVE
To review current research findings in cell biology, epidemiology, preclinical, and clinical trials on the protective effects of vitamin D against the development of cancers of the breast, colon, prostate, lung, and ovary. Current recommendations for optimal vitamin D status, the movement towards revision of standards, and reflections on healthy exposure to sunlight are also reviewed. Search methodology: A literature search was conducted in April and updated in September 2007. The Medline and Web of Knowledge databases were searched for primary and review articles published between 1970 and 2007, using the search terms 'vitamin D', 'calcitriol', 'cancer', 'chemoprevention', 'nuclear receptor', 'vitamin D receptor', 'apoptosis', 'cell cycle', 'epidemiology', and 'cell adhesion molecule'. Articles that focused on epidemiological, preclinical, and clinical evidence for vitamin D's effects were selected and additional articles were obtained from reference lists of the retrieved articles.


RESULTS
An increasing body of research supports the hypothesis that the active form of vitamin D has significant, protective effects against the development of cancer. Epidemiological studies show an inverse association between sun exposure, serum levels of 25(OH)D, and intakes of vitamin D and risk of developing and/or surviving cancer. The protective effects of vitamin D result from its role as a nuclear transcription factor that regulates cell growth, differentiation, apoptosis and a wide range of cellular mechanisms central to the development of cancer. A significant number of individuals have serum vitamin D levels lower than what appears to protect against cancer, and the research community is currently revising the guidelines for optimal health. This will lead to improved public health policies and to reduced risk of cancer.


CONCLUSIONS
Research strongly supports the view that efforts to improve vitamin D status would have significant protective effects against the development of cancer. The clinical research community is currently revising recommendations for optimal serum levels and for sensible levels of sun exposure, to levels greater than previously thought. Currently, most experts in the field believe that intakes of between 1000 and 4000 IU will lead to a more healthy level of serum 25(OH)D, at approximately 75 nmol/L that will offer significant protection effects against cancers of the breast, colon, prostate, ovary, lungs, and pancreas. The first randomized trial has shown significant protection against breast cancer, and other clinical trials will follow and ultimately lead to improved public health policies and significantly fewer cancers.
University of Maine, Orono, ME 04469-5737, USA. bingraham@umche.maine.edu
Betty A
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Ingraham
Beth
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Bragdon
Anja
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D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics*; D016021:Epidemiologic Studies; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000235:genetics / Q000517:prevention & control*; D016032:Randomized Controlled Trials as Topic; D018167:Receptors, Calcitriol / Q000235:genetics / Q000502:physiology; D013472:Sunlight; D014807:Vitamin D / Q000502:physiology / Q000600:supply & distribution / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D015815:Cell Adhesion Molecules; D018167:Receptors, Calcitriol; D014807:Vitamin D