What is the Dose-Response Relationship between Vitamin D and Cancer Risk?

An inverse association between serum 25-hydroxyvitamin D [25(OH)D], and risk of cancers of the colon, breast, and ovary has been reported in wellconducted observational studies.1 These studies have been supported by numerous natural experiments, specifically, studies that examine differences in incidence rates according to naturally occurring variations among populations in their ambient exposure to solar ultraviolet B irradiance, the main source of vitamin D.2-6 The presence of a dose-response gradient is one of the key criteria for determining whether an association is causal. Vitamin D is essential for the expression of proteins involved in expression of intercellular junctions such as E-cadherin.19,20 Tissue culture systems of normal epithelial cells have confirmed that tight junctions, desmosomes, and gap junctions are the most common junctions between epithelial cells.20 The proteins that constitute junctional systems decline when the concentration of vitamin D metabolites is low.19,20 In the absence of intact intercellular junctions, epithelial cells may separate, lose their normal cuboidal architecture, and acquire an increasingly amorphous architecture, with loss of function and apical-basal polarity.21 This phenomenon has been termed decoupling.\n Concern about such a slow-growing malignancy would be irrelevant.