Associations between circulating 1,25(OH)₂D concentration and odds of metachronous colorectal adenoma

Cellular-level studies demonstrate that the availability of the secosteroid hormone 1α,25-dihydroxyvitamin D [1,25(OH)₂D] to colon cells promotes anti-carcinogenic activities. Although epidemiological data are relatively sparse, suggestive inverse trends have been reported between circulating 1,25(OH)₂D concentration and colorectal neoplasia. We therefore sought to evaluate the relationship between circulating 1,25(OH) ₂D concentrations and odds for metachronous colorectal adenomas among 1,151 participants from a randomized trial of ursodeoxycholic acid for colorectal adenoma prevention. No relationship between 1,25(OH)₂D and overall odds for metachronous lesions was observed, with ORs (95 % CIs) of 0.80 (0.60-1.07) and 0.81 (0.60-1.10) for participants in the second and third tertiles, respectively, compared with those in the lowest (p-trend = 0.17). However, a statistically significant inverse association was observed between circulating 1,25(OH)₂D concentration and odds of proximal metachronous adenoma, with an OR (95 % CI) of 0.71 (0.52-0.98) for individuals in the highest tertile of 1,25(OH)₂D compared with those in the lowest (p-trend = 0.04). While there was no relationship overall between 1,25(OH)₂D and metachronous distal lesions, there was a significantly reduced odds for women, but not men, in the highest 1,25(OH)₂D tertile compared with the lowest (OR 0.53; 95 % CI 0.27-1.03; p-trend = 0.05; p-interaction = 0.08). The observed differences in associations with proximal and distal adenomas could indicate that delivery and activity of vitamin D metabolites in different anatomic sites in the colorectum varies, particularly by gender. These results identify novel associations between 1,25(OH) ₂D and metachronous proximal and distal colorectal adenoma, and suggest that future studies are needed to ascertain potential mechanistic differences in 1,25(OH)₂D action in the colorectum.