Prediagnostic circulating concentrations of vitamin D binding protein and survival among colorectal cancer patients

BACKGROUND: Higher total 25-hydroxyvitamin D [25(OH)D] levels are associated with improved survival among colorectal cancer (CRC) patients, but the relationships between circulating vitamin D binding protein (VDBP), bioavailable or free 25(OH)D, and CRC survival remain unknown. METHODS: We examined the associations between prediagnostic plasma levels of vitamin D-related markers and survival among 603 white participants diagnosed with CRC from 2 prospective US cohorts. Plasma VDBP and total 25(OH)D were directly measured, while bioavailable and free 25(OH)D were calculated using a validated formula based on total 25(OH)D, VDBP, and albumin levels. Cox proportional hazards regression was used to estimate hazard ratios (HRs) for overall and CRC-specific mortality, adjusted for other prognostic markers and potential confounders. RESULTS: Higher VDBP levels were associated with improved overall (P(trend) = 0.001) and CRC-specific survival (P(trend) = 0.02). Compared to patients in the lowest quartile, those in the highest quartile of VDBP had a multivariable HR of 0.58 (95% confidence interval [CI], 0.41–0.80) for overall mortality and 0.58 (95% CI, 0.37–0.91) for CRC-specific mortality. The results remained similar after further adjustment for total 25(OH)D levels. In contrast, neither bioavailable nor free 25(OH)D levels were associated with overall or CRC-specific mortality (all P(trend) > 0.15). CONCLUSION: Prediagnostic circulating concentrations of VDBP were positively associated with survival among CRC patients. IMPACT: The clinical utility of VDBP as a prognostic marker warrants further exploration, as well as research into underlying mechanisms of action.