Predictors of 25-hydroxyvitamin D and its association with risk factors for prostate cancer: evidence from the Prostate testing for cancer and Treatment study
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Circulating 25-hydroxyvitamin D (25(OH)D) may protect against prostate and other cancers. Few epidemiology studies have measured 25(OH)D on all participants, weakening the evidence-base through reduced statistical power and the potential for bias. We developed a score to predict individual 25(OH)D based on potential predictors, including sun exposure, nutrient intake, and vitamin D pathway genes, providing a method of substituting missing values. We assessed the usefulness of predicted 25(OH)D by comparison with multiple imputation of 25(OH)D levels.
Amongst 1,091 controls from a population-based case–control study (ProtecT), we quantified relationships of sun exposure, demographic, clinical, anthropologic, nutrient, and genetic data with circulating 25(OH)D and constructed several prediction scores from subsets of these measures. We investigated associations of three prostate cancer risk factors (PSA level, BMI, family history of prostate cancer) with 25(OH)D levels in sensitivity analyses based upon participants with measured 25(OH)D only and based upon the addition of all participants with missing 25(OH)D levels substituted by prediction score values or by multiple imputation.
Our score accounted for 27.7% of the variation in measured 25(OH)D. Associations with risk factors of prostate cancer were consistent across the different estimates of 25(OH)D. However, standard deviations for the prediction score did not incorporate extra error from prediction. Multiple imputation of missing 25(OH)D values predicted a more realistic range of 25(OH)D.
In epidemiological studies of cancer risk associated with vitamin D, multiple imputation of missing 25(OH)D is preferable to prediction scores, as a wider range of 25(OH)D levels are imputed and appropriate confidence intervals calculated.
KeywordsProstate cancer Prostatic neoplasms Vitamin D 25-Hydroxyvitamin D Calcifediol
This analysis was funded by the World Cancer Research Fund UK (Grant number 2006/15). RG is recipient of a Cancer Research UK Graduate Training Fellowship (C31211/A10095). The UK Department of Health funded the ProtecT study through the NIHR Health Technology Assessment programme. Freddie Hamdy, Jenny Donovan, and David Neal are NIHR Senior Investigators. The authors would like to acknowledge the provision of additional epidemiological data by the NHS R&D Directorate supported Prodigal study and the ProMPT (Prostate Mechanisms of Progression and Treatment) collaboration, which is supported by the National Cancer Research Institute (NCRI) formed by the Department of Health, the Medical Research Council and Cancer Research, UK. 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, and 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..
Conflicts of interest
The authors declare that they have no conflict of interest.
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