We hypothesized that low <i>CYP27A1</i> expression is associated with high cholesterol synthesis, low vitamin D signaling, and higher risk of lethal prostate cancer.
Our findings suggest that CYP27A1 is a critical cellular cholesterol sensor in prostate cells and that dysregulation of the CYP27A1/27HC axis contributes significantly to prostate cancer pathogenesis.<i></i>.
Pathway analyses found that the set of SNPs that included all seven genes (P = .008) as well as sets of SNPs that included VDR (P = .01) and CYP27A1 (P = .02) were associated with risk of lethal prostate cancer.
We systematically investigated the association of 48 SNPS in four vitamin D metabolizing genes [CYP27A1, GC, CYP27B1 and CYP24A1] with serum 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)(2)D] levels and the association of these SNPS and an additional 164 SNPS in eight downstream mediators of vitamin D signaling [VDR, RXRA, RXRB, PPAR, NCOA1, NCOA2, NCOA3 and SMAD3] with prostate cancer risk in the 749 incident prostate cancer cases and 781 controls of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial.