Prediagnostic Vitamin D Status and Colorectal Cancer Survival by Vitamin D Binding Protein Isoforms in US Cohorts

Context Lower 25-hydroxyvitamin D (25(OH)D) levels have consistently been associated with higher mortality among participants with colorectal cancer (CRC). Objective To investigate whether the association between 25(OH)D and CRC mortality differs according to vitamin D binding protein (also known as Gc) isoforms. Methods We examined the association between prediagnostic 25(OH)D levels and overall and CRC-specific mortality among participants with CRC within 2 prospective US cohorts. Cox proportional hazards regression was used to estimate the hazard ratios (HRs) and 95% CIs. Results 588 participants with CRC were observed until the date of death or last follow-up (2018), whichever came first. Deficient vs sufficient 25(OH)D concentrations (<30 vs >= 50 nmol/L) were associated with higher overall mortality (HR 2.06; 95% CI 1.34-3.18) but not with CRC-specific mortality (HR 1.51; 95% CI 0.75-3.07). The HRs for overall mortality comparing deficient vs sufficient concentrations were 2.43 (95% CI 1.26-4.70) for those with the Gc1-1 isoform (rs4588 CC) and 1.63 (95% CI 0.88-3.02) for those with the Gc1-2 or Gc2-2 (rs4588 CA or AA) isoform (P for interaction = .54). The HRs for CRC-specific mortality were 1.18 (95% CI 0.27-5.14) for those with the Gc1-1 isoform and 1.41 (95% CI 0.62-3.24) for those with the Gc1-2 or Gc2-2 isoform (P for interaction = .94). Conclusion In these 2 US cohorts, we found that lower 25(OH)D levels were associated with higher overall mortality, but this association did not differ by Gc isoforms.