Public Release: 

Low vitamin D levels linked to increased risk of bladder cancer

University of Warwick

Vitamin D deficiency is associated with an increased risk of developing bladder cancer, according to a systematic review of seven studies presented today at the Society for Endocrinology annual conference in Brighton. Though further clinical studies are needed to confirm the findings, the study adds to a growing body of evidence on the importance of maintaining adequate vitamin D levels.

Vitamin D, which is produced by the body through exposure to sunshine, helps the body control calcium and phosphate levels. Vitamin D can also be obtained from food sources such as fatty fish and egg yolks. Previous studies have linked vitamin D deficiency with a host of health problems including cardiovascular disease, cognitive impairment, autoimmune conditions, and cancer.

In countries with low levels of sunlight, it is difficult to obtain enough vitamin D from food alone. In the UK, 1 in 5 adults are vitamin D deficient and 3 in 5 have low levels. This is especially prevalent in people with darker skin: in winter, 75% of dark-skinned people in the UK are vitamin D deficient.

In this work, researchers from the University of Warwick and University Hospital Coventry and Warwickshire, Coventry and the investigated the link between vitamin D and bladder cancer risk. They reviewed seven studies on the topic which ranged from having 112 to 1125 participants each. Five out of the seven studies linked low vitamin D levels to an increased risk of bladder cancer.

In a separate experiment, the researchers then looked at the cells that line the bladder, known as transitional epithelial cells, and found that these cells are able to activate and respond to vitamin D, which in turn can stimulate an immune response. According to lead author of the study Dr Rosemary Bland, this is important because the immune system may have a role in cancer prevention by identifying abnormal cells before they develop into cancer.

"More clinical studies are required to test this association, but our work suggests that low levels of vitamin D in the blood may prevent the cells within the bladder from stimulating an adequate response to abnormal cells," said Dr Bland. "As vitamin D is cheap and safe, its potential use in cancer prevention is exciting and could potentially impact on the lives of many people."

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Abstract

P129

Low vitamin D is associated with increased bladder cancer risk; a systematic review and evidence of a potential mechanism.

Rosemary Bland1,2, Corina Chivu1, Kieran Jefferson2, Donald MacDonald2, Gulnaz Iqbal1 & Janet Dunn1

1The University of Warwick, Coventry, UK; 2University Hospital Coventry and Warwickshire, Coventry, UK.

Vitamin D deficiency is associated with the development of some cancers and in vitro 1,25-dihydroxyvitamin D (1,25D) reduces cell proliferation. We suggest that modification of tissue specific immune responses, as a consequence of local synthesis of 1,25D, may be key.

To assess the impact of serum 25D on the risk of bladder cancer we conducted a systematic review. To test our hypothesis, expression of vitamin D signalling components and the synthesis of 1,25D were examined in human bladder epithelial cell lines (T24/83 and RT4). A search of Embase, Web of Science, Medline and Cochrane library (April-May 2016) identified 287 citations.

Following title and abstract review by 2 reviewers 7 full papers were appraised. Studies varied in the number of participants (112-1125) and point of vitamin D measurement (pre-diagnosis, diagnosis, or follow-up). Low vitamin D levels were associated with bladder cancer risk in 5 of the 7 studies.

Higher vitamin D levels also correlated with better survival and outcomes. The vitamin D receptor and 25-hydroxyvitamin D 1α-hydroxylase (CYP27B1; 1α-OHase) mRNA and protein were expressed by both cell lines. 24-hydroxylase (24-OHase; metabolises 1,25D) mRNA was almost undetectable in unstimulated cells but was increased significantly by 1,25D (10nM, 3-24 hours; p<0.05). 24-OHase was also induced by 25D (100nM, 6-24 hours; p<0.05) indicating 1α-OHase activity.

Synthesis of 1,25D was confirmed by EIA. Cathelicidin mRNA was induced by 1,25D and 25D in RT4 cells (10nM/100nM, 6 hours; p<0.05). These data demonstrate that bladder cancer risk correlates with low serum 25D levels. Transitional epithelial cells express functional vitamin D signalling and are able to synthesize sufficient 1,25D to stimulate a local immune response. We propose that in order to initiate a cell-mediated immune response to malignancy adequate levels of serum 25D are required for synthesis of 1,25D by bladder epithelial cells.

Notes for editors

1. For further information about the study please contact:

Dr Rosemary Bland
Honorary Associate Professor
University of Warwick
Tel: +44 07506102426
Email: rosemary.bland1@gmail.com

2. The study Low vitamin D is associated with increased bladder cancer risk; a systematic review and evidence of a potential mechanism is a poster presented by Dr Rosemary Bland at the Society for Endocrinology's annual conference. Please note this is a conference abstract, and this study has not yet been published in a peer-reviewed journal.

3. For press enquiries, please contact the Society for Endocrinology press office:

Omar Jamshed
Communications Executive
Tel: +44 (0)1454 642 206 (office)
Tel: +44 (0) 7876824027 (mobile)
Email: omar.jamshed@endocrinology.org

University of Warwick Medial Relations Manager
Nicola Jones
email: N.Jones.1@warwick.ac.uk
Mobile: 07920531221

4. The Society for Endocrinology's annual conference is held at the Brighton Conference Centre from 7-9 November 2016. The conference features some of the world's leading basic and clinical endocrinologists who present their work. Journalists wishing to attend should contact the Society for Endocrinology press office using the details above. The scientific programme is available on the conference webpage.

5. The Society for Endocrinology is a UK-based membership organisation representing a global community of scientists, clinicians and nurses who work with hormones. Together we aim to improve public health by advancing endocrine education and research, and engaging wider audiences with the science of hormones. http://www.endocrinology.org

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