Bladder cancer risk is associated with low serum 25-hydroxyvitamin D levels; a systematic review


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Corina Chivu1,Janet Dunn1,Bland Rosemary1,Kieran Jefferson2,Donald MacDonald2,Gulnaz Iqbal1
1University of Warwick,2Department of Urology, University Hospital Coventry and Warwickshire, Coventry



Vitamin D deficiency (low levels of serum 25-hydroxyvitamin D; 25D) is associated with the development of some cancers. Although the mechanism is not well understood local conversion of 25D to active vitamin D (1,25-dihydroxyvitamin D; 1,25D) and the modification of tissue specific immune responses may be key; non- muscle-invasive bladder cancer is highly immunoresponsive. We have previously shown that bladder epithelial cells express functional vitamin D signalling and are able to synthesize sufficient 1,25D to stimulate a local immune response.  To assess the clinical impact of serum 25D on the risk of bladder cancer we conducted a systematic review.


Studies were identified from Medline, Embase, Web of Science and Cochrane Library limited to English language, humans and 1995-2016. Studies included randomized controlled trials and observational studies, evaluating serum level of vitamin D (25D) and bladder cancer risk. Data in relation to characteristics of studies, participants, interventions, and outcomes were extracted by two independent reviewers. Reviews were excluded.


The initial search identified 287 citations. After removal of duplicates and title and abstract review 10 met the inclusion criteria. Following review of the full text, 3 further papers were excluded. Studies varied in the number of participants (500-9791), and point of vitamin D measurement (pre-diagnosis, diagnosis, or follow-up). Included studies were conducted between 2000-2016. Low vitamin D levels were associated with bladder cancer risk in 5 of the 7 studies. Importantly higher vitamin D levels also correlated with better survival and outcomes.


These data demonstrate that bladder cancer risk correlates with serum 25D levels. We suggest that in order to maintain optimal immune surveillance within the bladder adequate levels of serum 25D are required for direct synthesis of 1,25D by bladder epithelial cells. We propose that vitamin D supplementation presents a new therapy for bladder cancer.