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Plasma vitamin D and prostate cancer risk: results from the Selenium and Vitamin E Cancer Prevention Trial

Kristal AR, Till C, Song X, Tangen CM, Goodman PJ, Neuhauser ML, Schenk JM, Thompson IM, Meyskens FL Jr, Goodman GE, Minasian LM, Parnes HL, Klein EA.

Cancer Epidemiol Biomarkers Prev. 2014;23:1494-504



In vitro, animal, and ecological studies suggest that inadequate vitamin D intake could increase prostate cancer risk, but results of biomarker-based longitudinal studies are inconsistent.


Data for this case (n = 1,731) and cohort (n = 3,203) analysis are from the Selenium and Vitamin E Cancer Prevention Trial. Cox proportional hazard models were used to test whether baseline plasma vitamin D (25-hydroxy) concentration, adjusted for season of blood collection, was associated with the risk of total and Gleason score 2-6, 7-10, and 8-10 prostate cancer.


There were U-shaped associations of vitamin D with total cancer risk: compared with the first quintile, HRs were 0.83 [95% confidence interval (CI), 0.66-1.03; P = 0.092], 0.74 (95% CI, 0.59-0.92; P = 0.008), 0.86 (95% CI, 0.69-1.07; P = 0.181), and 0.98 (95% CI, 0.78-1.21; P = 0.823), for the second through fifth quintiles, respectively. For Gleason 7-10 cancer, corresponding HRs were 0.63 (95% CI, 0.45-0.90; P = 0.010), 0.66 (95% CI, 0.47-0.92; P = 0.016), 0.79 (95% CI, 0.56-1.10; P = 0.165), and 0.88 (95% CI, 0.63-1.22; P = 0.436). Among African American men (n = 250 cases), higher vitamin D was associated with reduced risk of Gleason 7-10 cancer only: in the a posteriori contrast of quintiles 1-2 versus 3-5, the HR was 0.55 (95% CI, 0.31-0.97; P = 0.037), with no evidence of dose-response or a U-shaped association.


Both low and high vitamin D concentrations were associated with increased risk of prostate cancer, and more strongly for high-grade disease.


The optimal range of circulating vitamin D for prostate cancer prevention may be narrow. Supplementation of men with adequate levels may be harmful. Cancer Epidemiol Biomarkers Prev; 23(8); 1494-504. ©2014 AACR.

©2014 American Association for Cancer Research.

Comment from Henk van der Poel: Both low and high Vit D plasma levels found to increase prostate cancer risk in the SELECT trial population. Vit D supplementation may increase PCA risk.

In the PCPT trial elevated serum vit D levels were also associated with increased incidence of Gleason 2-6 but with a reduced risk of Gleason 8-10 cancers in both the placebo and finasteride study arm.

It is suggested that this apparent contradiction is caused by selection bias in the SELECT trial population (Schwartz cancer epidemiol biom prev 23:1447, 2014) and that indeed vit D may decrease the incidence of higher risk prostate cancer as suggested by the PCPT findings.