Associations of circulating 25‐hydroxyvitamin D with prostate cancer diagnosis, stage and grade

Abstract Epidemiological studies suggest that vitamin D protects against prostate cancer, although evidence is limited and inconsistent. We investigated associations of circulating total 25‐hydroxyvitamin D (25(OH)D) with prostate specific antigen‐detected prostate cancer in a case‐control study nested within the prostate testing for cancer and treatment (ProtecT) trial. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) quantifying the association between circulating total 25(OH)D and prostate cancer. In case‐only analyses, we used unconditional logistic regression to quantify associations of total 25(OH)D with stage (advanced vs. localized) and Gleason grade (high‐grade (≥7) vs. low‐grade (<7)). Predetermined categories of total 25(OH)D were defined as: high: ≥30 ng/mL; adequate: 20 – <30 ng/mL; insufficient: 12 – <20 ng/mL; deficient: <12 ng/mL. Fractional polynomials were used to investigate the existence of any U‐shaped relationship. We included 1,447 prostate cancer cases (153 advanced, 469 high‐grade) and 1,449 healthy controls. There was evidence that men deficient in vitamin D had a 2‐fold increased risk of advanced versus localized cancer (OR for deficient vs. adequate total 25(OH)D = 2.33, 95% CI: 1.26, 4.28) and high‐grade versus low‐grade cancer (OR for deficient vs. adequate total 25(OH)D = 1.78, 95% CI: 1.15, 2.77). There was no evidence of a linear association between total 25(OH)D and prostate cancer ( p = 0.44) or of an increased risk of prostate cancer with high and low vitamin D levels. Our study provides evidence that lower 25(OH)D concentrations were associated with more aggressive cancers (advanced versus localized cancers and high‐ versus low‐Gleason grade), but there was no evidence of an association with overall prostate cancer risk.