African Americans have the greatest colorectal cancer (CRC) burden in the United States—inter-ethnic differences in protective effects of vitamin D might contribute to disparities. 1α,25(OH)2D3 vitamin D (the active form of vitamin D) induces transcription of the uridine phosphorylase gene (UPP1) in colon tissues from European Americans, but to a lesser extent in colon tissues from African Americans. UPP1-knockout mice have increased intestinal concentrations of uridine and dUTP, increased uridine-induced DNA damage, and develop colon tumors.