Plasma 1,25-dihydroxy- and 25-hydroxyvitamin D and subsequent risk of prostate cancer

Objective: The hormone 1,25-dihydroxyvitamin D (1,25(OH)(2)D) promotes prostate epithelial cell differentiation in vitro and thus, several groups have hypothesized that men who systemically have lower levels of 1,25( OH) 2D may be at increased risk for prostate cancer. To address this hypothesis, we evaluated the association of circulating concentrations of 1,25(OH)(2)D and its precursor 25-hydroxyvitamin D (25(OH)D) with subsequent risk of prostate cancer. Methods: Prostate cancer cases were 460 men in the Health Professionals Follow-up Study who were diagnosed through 1998 after providing a blood specimen in 1993/95. 90.2% of the cases were organ confined or had minimal extraprostatic extension. An equal number of controls who had had a screening PSA test after blood draw were individually matched to cases on age, history of a PSA test before blood draw, and time of day, season, and year of blood draw. Plasma 1,25(OH)(2)D and 25( OH) D concentrations were determined by radio-immunosorbant assay blindly to case - control status. Odds ratios ( OR) of prostate cancer and 95% confidence intervals (CI) were estimated from conditional logistic regression models mutually adjusting for quartiles of 1,25(OH)(2)D and 25( OH) D concentrations and for suspected prostate cancer risk factors. Quartile cutpoints were determined separately by season of blood draw using the distributions among controls. Results: Mean concentrations of 1,25(OH)(2)D and 25(OH) D were slightly, but not statistically significantly (p = 0.06 and 0.20, respectively), higher in cases (34.3 +/- 7.1 pg/ml and 24.6 +/- 7.7 ng/ml, respectively) than in controls (33.5 +/- 7.1 pg/ml and 23.9 +/- 8.2 ng/ml, respectively). The OR of prostate cancer comparing men in the top to bottom quartile of 1,25(OH)(2)D was 1.25 (95% CI: 0.82 - 1.90, p-trend = 0.16). For 25(OH) D the OR of prostate cancer comparing the top and bottom quartiles was 1.19 ( 95% CI: 0.79 - 1.79, p- trend = 0.59). These findings did not vary by level of the other metabolite, age at diagnosis, family history of prostate cancer, or factors that are thought to influence 25(OH) D levels. Conclusion: In this prospective study, we did not observe an inverse association between plasma concentrations of 1,25(OH)(2)D or 25(OH) D and incident prostate cancer, although we cannot rule out potential effects at later stages of the disease.