R Gilbert, C Metcalfe, WD Fraser, J Donovan, F Hamdy, DE Neal, JA Lane, RM Martin
Cancer Causes Control
PURPOSE: Some epidemiological studies suggest that vitamin A (retinol), vitamin E, and vitamin D (total 25-hydroxyvitamin D, 25(OH)D; 1,25-dihydroxyvitamin, 1,25(OH)(2)D) are protective against prostate cancer. However, the evidence is not conclusive, with positive and null associations reported for all three vitamins. Limitations of previous studies include small sample size, lack of population controls, and reliance on self-reported dietary intake. Few studies have explored the interactions of circulating 25(OH)D with 1,25(OH)(2)D or retinol, which are biologically plausible interactions. METHODS: We investigated the associations of circulating retinol, vitamin E, and 1,25(OH)(2)D with PSA-detected prostate cancer risk, stage, and grade in a case-control study nested within the Prostate Testing for Cancer and Treatment (ProtecT) trial. We investigated the possibility of an interaction between 25(OH)D and 1,25(OH)(2)D and whether the previously observed association between 25(OH)D and prostate cancer may be modified by retinol levels. RESULTS: We included 1,433 prostate cancer cases and 1,433 healthy controls. There was no evidence of associations of circulating retinol, vitamin E, or 1,25(OH)(2)D with overall prostate cancer risk, stage (advanced vs localized), or Gleason grade (high- (≥7) vs low (<7) grade). There was no evidence of an interaction of 1,25(OH)(2)D and 25(OH)D with prostate cancer risk, stage, or grade (p interaction ≥ 0.24). The association between 25(OH)D and prostate cancer did not differ by retinol level (p interaction = 0.34). CONCLUSIONS: We found no evidence that retinol, vitamin E, or 1,25(OH)(2)D concentrations were associated with overall prostate cancer risk or more aggressive prostate cancer phenotypes. There was no evidence of an interaction between 25(OH)D and 1,25(OH)(2)D or retinol.