Associations of circulating retinol, vitamin E, and 1,25-dihydroxyvitamin D with prostate cancer diagnosis, stage, and grade
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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)2D) 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)2D or retinol, which are biologically plausible interactions.
We investigated the associations of circulating retinol, vitamin E, and 1,25(OH)2D 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)2D and whether the previously observed association between 25(OH)D and prostate cancer may be modified by retinol levels.
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)2D 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)2D 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).
We found no evidence that retinol, vitamin E, or 1,25(OH)2D 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)2D or retinol.
KeywordsProstate cancer Vitamin D 1,25-Dihydroxyvitamn D Retinol Vitamin E
Prostate Testing for Cancer and Treatment trial
Nanograms per milliliter
Nanomoles per liter
Picomoles per liter
95 % Confidence intervals
Body mass index
Mean arterial pressure
This analysis was funded by the World Cancer Research Fund, United Kingdom (Grant number 2006/15). RG is recipient of a Cancer Research UK Graduate Training Fellowship (C31211/A10095). Development of models for PSA was funded by the National Institute for Health Research Health Services Research programme (project 09/2000/63). The UK Department of Health funded the ProtecT study through the NIHR Health Technology Assessment programme. Ethics approvals for ProtecT and ProMPT: All men provided written informed consent prior to inclusion in the study. Trent Multicentre Research Ethics Committee (MREC) approved the ProtecT study (MREC/01/4/025) and the associated ProMPT study, which collected biological material (MREC/01/4/061). The authors would like to acknowledge the provision of additional epidemiological data by the NHS R&D Directorate supported Prodigal study. Also, the ProMPT (Prostate Mechanisms of Progression and Treatment, grant code G0500966/75466) collaboration which has funded tissue and urine collections and is supported by the National Cancer Research Institute (NCRI) formed by the Department of Health, the Medical Research Council and Cancer Research UK. These collaborations are supported by the University of Cambridge Cancer Research, United Kingdom, and the National Institute for Health Research funded Cambridge Bio-medical Research Centre, Cambridge, United Kingdom. The authors would like to acknowledge the tremendous contribution of all members of the ProtecT study research group, and especially the following who were involved in this research (Prasad Bollina, Sue Bonnington, Lynn Bradshaw, James Catto, Debbie Cooper, Michael Davis, Liz Down, Andrew Doble, Alan Doherty, Garrett Durkan, Emma Elliott, David Gillatt, Pippa Herbert, Peter Holding, Joanne Howson, Mandy Jones, Roger Kockelbergh, Howard Kynaston, Teresa Lennon, Norma Lyons, Hing Leung, Malcolm Mason, Hilary Moody, Philip Powell, Alan Paul, Stephen Prescott, Derek Rosario, Patricia O’Sullivan, Pauline Thompson, Sarah Tidball). They would also like to thank Gemma Marsden, who processed the blood samples at the biorepository. Department of Health disclaimer: The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the Department of Health.
Conflict of interest
The authors declare that they have no conflict of interest.
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