ORIGINAL PAPER Predictors of 25-hydroxyvitamin D and its association with risk factors for prostate cancer: evidence from the Prostate testing for cancer and Treatment study Rebecca Gilbert • Richard M. Martin • William D. Fraser • Sarah Lewis • Jenny Donovan • Freddie Hamdy • David E. Neal • J. Athene Lane • Chris Metcalfe Received: 12 October 2011 / Accepted: 9 February 2012 / Published online: 1 March 2012 Ó Springer Science+Business Media B.V. 2012 Abstract Purpose Circulating 25-hydroxyvitamin D (25(OH)D) may protect against prostate and other cancers. Few epi- demiology studies have measured 25(OH)D on all partic- ipants, 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 substi- tuting missing values. We assessed the usefulness of pre- dicted 25(OH)D by comparison with multiple imputation of 25(OH)D levels. Methods 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. Results 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 esti- mates of 25(OH)D. However, standard deviations for the prediction score did not incorporate extra error from pre- diction. Multiple imputation of missing 25(OH)D values predicted a more realistic range of 25(OH)D. Conclusion 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. Keywords Prostate cancer Á Prostatic neoplasms Á Vitamin D Á 25-Hydroxyvitamin D Á Calcifediol Introduction Ecological studies report inverse relationships between living at latitudes close to the equator and prostate cancer mortality [1, 2], leading to speculation that total circulating 25-hydroxyvitamin D (25(OH)D), approximately 80–90% Electronic supplementary material The online version of this article (doi:10.1007/s10552-012-9919-8) contains supplementary material, which is available to authorized users. R. Gilbert (&) Á R. M. Martin Á S. Lewis Á J. Donovan Á J. A. Lane Á C. Metcalfe 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 R. M. Martin Á S. Lewis MRC Centre for Causal Analysis in Translational Epidemiology, School of Social and Community Medicine, University of Bristol, Bristol, UK W. D. Fraser Norwich Medical School, Faculty of Medicine and Health Sciences, 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) 23:575–588 DOI 10.1007/s10552-012-9919-8