Accumulated evidence from laboratory and human investigations supports the hypothesis that \#8220;low\#8221; vitamin D status (from dietary intake or UV induced synthesis) enhances prostate cancer risk. Although less consistent, several studies suggest that high calcium status is also associated with increased prostate cancer risk. In this study, we examined the effects of varying dietary vitamin D and calcium on the carcinogenic process in the transgenic APT121 murine model with a variant of the SV40 large -T antigen driven by the androgen responsive probasin promoter. These mice develop hyperproliferative and dysplastic lesions with focal areas of adenocarcinoma. A 3 x 3 factorial design experiment was completed in mice fed one of 9 diets (n = 30 per diet) varying in dietary vitamin D (25, 150 or 1,000 IU/kg vitamin D) or calcium (0.2%, 0.5% or 1.5% calcium) from 4 - 28 weeks of age. Food intake and growth were similar in all treatment groups. Our preliminary analysis suggests that increasing dietary vitamin D lowered the risk of prostate adenocarcinoma (incidence of adenocarcinoma: 95%, 86% and 69% for 25, 150 and 1000 IU /kg, respectively) while increasing the percentage of mice with hyperplasia or PIN as the most advanced lesion. Although less striking, increased levels of dietary calcium are associated with a trend toward worsening prostate pathology, particularly in the setting of low dietary vitamin D. However, femur bone DEXA analysis showed greater density with increasing calcium, with minimal impact of vitamin D. Our study supports the hypothesis that high dietary vitamin D has a beneficial effect on the early stages of prostate carcinogenesis in vivo and that high calcium diets may modestly attenuate the anti-carcinogenic effects of 1,25(OH)2D while having a beneficial impact upon bone density. Support from NIH/NCI 5R01CA101113-05, AICR 05A131, Schoen Cancer Prevention Fund (246394) at the Arthur James Cancer Hospital and Solove Research Institute.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 42.

100th AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO