Association among plasma 1,25(OH)₂D, ratio of 1,25(OH)₂D to 25(OH)D, and prostate cancer aggressiveness

Background: African-American (AA) men tend to present with more aggressive prostate cancer (Gleason score >7) than European-American (EA) men. Vitamin D and its metabolites are implicated in prostate cancer biology with vitamin D deficiency, indicated by its metabolite levels in serum or plasma, usually observed in AA men. Objective: To determine if 1, 25-dihydroxy vitamin D3 [1,25(OH)₂D] plasma levels in AA and EA prostate cancer patients alter the risk of having aggressive prostate cancer. Design: Research subjects from the North Carolina-Louisiana Prostate Cancer Project (AA n = 435 and EA n = 532) were included. Plasma metabolites 1,25(OH)₂D and 25-hydroxyvitamin D3 [25(OH)D] were measured using liquid chromatography with tandem mass spectrophotometry. Research subjects were classified into low (Gleason sum < 7, stage T1-T2, and Prostate-specific antigen (PSA) < 9 ng/mL) or high (Gleason sum > 8 or Gleason sum = 7 with 4 + 3, or PSA > 20 ng/mL, or Gleason sum = 7 and stage T3-T4) aggressive disease. Results: Research subjects in the second and third tertiles of plasma levels of 1, 25(OH)₂D had lower odds of high aggressive prostate cancer (AA [OR_T2vsT1: 0.66, 95%CI: 0.39-1.12; OR_T3vsT1: 0.83, 95%CI: 0.49-1.41] and EA [OR_T2vsT1: 0.68, 95%CI: 0.41-1.11; OR_T3vsT1: 0.67, 95%CI: 0.40-1.11]) compared with the first tertile, though confidence intervals included the null. Greater 1,25(OH)₂D/25(OH)D molar ratios were associated with lower odds of high aggressive prostate cancer more evidently in AA (OR_Q4vsQ1: 0.45, CI: 0.24-0.82) than in EA (OR_Q4vsQ1: 0.64, CI: 0.35-1.17) research subjects. Conclusions: The 1,25(OH)₂D/25(OH)D molar ratio was associated with decreased risk of high aggressive prostate cancer in AA men, and possibly in EA men. Further studies analyzing vitamin D polymorphisms, vitamin D binding protein levels, and prostatic levels of these metabolites may be useful. These studies may provide a better understanding of the vitamin D pathway and its biological role underlying health disparities in prostate cancer.