Abstract B62: Circulating vitamin D binding protein, 25-hydroxyvitamin D, and advanced and lethal prostate cancer risk
Authors: Shui Irene , Wilson Kathryn , Stampfer Meir , Mucci Lorelei , Giovannucci Ed 
Published: May 2019

Abstract
Introduction: Circulating 25-hydroxyvitamin D (25(OH)D) is the most commonly accepted blood biomarker for vitamin D status in epidemiologic studies. We have previously shown that higher circulating 25(OH)D was related to a reduced risk of advanced and lethal prostate cancer (PCa). However, 85-90% of circulating 25(OH)D is bound to vitamin D-binding protein (DBP) and current laboratory assays do not differentiate between bound and unbound forms of 25(OH)D. The role of DBP on PCa remains unclear. DBP extends the half-life of circulating 25(OH)D, but it is not known whether DBP-bound vitamin D activity on prostate cells is less than in the unbound form. DBP circulates at much higher levels than 25(OH)D and may also have independent effects on prostate carcinogenesis. Using prospectively measured circulating DBP and 25(OH)D, we assessed whether DBP was related to advanced/lethal PCa and whether the relationship between 25(OH)D and advanced/lethal PCa was modified by DBP levels.
Methods: We included 164 men diagnosed with advanced (Stage T3b or higher) and lethal (distant metastases or PCa specific cause of death) PCa and 164 matched controls nested in the Health Professionals Follow-up Study. We used unconditional logistic regression, adjusted for matching factors, to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between DBP, 25(OH)D, and advanced/lethal PCa. We assessed effect modification by high and low 25(OH)D or DBP levels using the median value as the cut point.
Results: Circulating DBP and 25(OH)D were modestly correlated in controls (Spearman correlation=0.17; p=0.04). Consistent with our previous study, higher plasma 25(OH)D was associated with a reduced risk of advanced/lethal PCa (OR (95% CI) for highest vs. lowest quartile of 25(OH)D: 0.28 (0.14-0.57); p-trend &lt;0.0001); adjusting for circulating DBP did not change these results. The association between 25(OH)D and advanced/lethal PCa was not modified by DBP level (p-interaction=0.34). Plasma DBP was inversely associated with advanced and lethal PCa risk in those with high 25(OH)D levels (OR (95% CI) for highest vs. lowest quartile of DBP: 0.29(0.08-0.99); p-trend=0.03), but not in those with low 25(OH)D levels (OR (95% CI): 1.32(0.52-3.36); p-trend=0.73). The p-interaction was 0.0003.
Conclusions: Adjusting for circulating DBP did not influence the association between 25(OH)D and advanced/lethal PCa in our study. However, the role of DBP in prostate carcinogenesis warrants future investigation.
Citation Format: Irene Shui, Kathryn Wilson, Meir Stampfer, Lorelei Mucci, Ed Giovannucci. Circulating vitamin D binding protein, 25-hydroxyvitamin D, and advanced and lethal prostate cancer risk. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr B62.