BRIEF REPORT Associations of circulating retinol, vitamin E, and 1,25-dihydroxyvitamin D with prostate cancer diagnosis, stage, and grade Rebecca Gilbert • Chris Metcalfe • William D. Fraser • Jenny Donovan • Freddie Hamdy • David E. Neal • J. Athene Lane • Richard M. Martin Received: 25 May 2012 / Accepted: 9 August 2012 / Published online: 28 August 2012 Ó Springer Science+Business Media B.V. 2012 Abstract 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. How- ever, 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 popu- lation 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 biologi- cally 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 associ- ations of circulating retinol, vitamin E, or 1,25(OH) 2 D with overall prostate cancer risk, stage (advanced vs localized), or Gleason grade (high- (C7) 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 C 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. Keywords Prostate cancer Á Vitamin D Á 1,25-Dihydroxyvitamn D Á Retinol Á Vitamin E Abbreviations 25(OH)D 25-Hydroxyvitamin D 1,25(OH) 2 D 1,25-Dihydroxyvitamin D ProtecT Prostate Testing for Cancer and Treatment trial PSA Prostate-specific antigen ng/mL Nanograms per milliliter nmol/L Nanomoles per liter pmol/L Picomoles per liter OR Odds ratios CI 95 % Confidence intervals Electronic supplementary material The online version of this article (doi:10.1007/s10552-012-0052-5) contains supplementary material, which is available to authorized users. R. Gilbert (&) Á C. Metcalfe Á J. Donovan Á J. A. Lane Á R. M. Martin School of Social and Community Medicine, University of Bristol, Canynge Hall, 39 Whatley Road, Bristol BS8 2PS, UK e-mail: becky.gilbert@bristol.ac.uk W. D. Fraser Norwich Medical School, University of East Anglia, Norwich, UK F. Hamdy Nuffield Department of Surgery, University of Oxford, Oxford, UK D. E. Neal Department of Oncology, University of Cambridge, Cambridge, UK 123 Cancer Causes Control (2012) 23:1865–1873 DOI 10.1007/s10552-012-0052-5