Does testosterone mediate the relationship between vitamin D and prostate cancer?


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Luke Robles1,Sean Harrison1,Vanessa Tan1,Rhona Beynon1,Alexandra McAleenan1,Karen Dawe1,Tom Gaunt1,Julian Higgins1,Richard Martin1,Sarah Lewis1
1University of Bristol

Abstract

Background

Evidence from observational and experimental studies have shown an association between vitamin D and prostate cancer risk and progression. However, available studies are limited and have not examined biological mechanisms, which can provide insight into the robustness of this association and potential interventions.

Method

This review used the World Cancer Research Fund International/University of Bristol two-stage framework. In stage 1, a biological mechanism was identified using a bioinformatic approach (namely the Text Mining for Mechanism Prioritisation (TeMMPo)) tool (https://www.temmpo.org.uk/)), combined with expert opinion. In stage 2, a systematic literature review examined studies of the identified mechanism in relation to both vitamin D and prostate cancer. Meta-analyses were performed on studies with usable data. 

Results

In stage 1, TeMMPo showed the term ‘testosterone’ had a substantial number of publications with both vitamin D and prostate cancer terms and was identified as a potential mechanism. In stage 2, 32 studies were reviewed. Six studies examined the vitamin D-testosterone association and were all, except one, randomised controlled trials. Meta-analyses showed no strong evidence of associations of vitamin D with total (SMD = 0.18, 95% CI = -0.04, 0.40) or free (SMD = 0.02, 95% CI = -0.30, 0.34) testosterone. Twenty-six studies (21 observational, 5 rodent) examined the testosterone-prostate cancer association. Meta-analyses showed no strong evidence of associations between total (OR = 0.99, 95% CI = 0.94, 1.05) or free (OR = 1.01, 95% CI = 0.93, 1.11) testosterone and prostate cancer risk. A summary of findings from studies measuring progression showed both high and low doses of testosterone to increase progression.

Conclusion

There was no strong evidence of the vitamin D-prostate cancer association operating through testosterone. However, estimates for the vitamin D-testosterone studies were imprecise and the strength of this association was inconclusive according to the grading of recommendations assessment, development and evaluation (GRADE). In addition, the strength of the evidence for the testosterone-prostate cancer studies was considered weak.