Prediagnostic vitamin D status and colorectal cancer survival by vitamin D-binding protein isoforms in the US cohorts


 
 
 Lower 25-hydroxyvitamin D [25(OH)D] levels have consistently been associated with higher mortality among participants with colorectal cancer (CRC). However, it is still unknown whether this association differs by vitamin-D binding protein (also known as Gc) isoforms.
 
 
 
 We examined the association between prediagnostic 25(OH)D levels and overall and CRC-specific mortality among participants with CRC within two prospective US cohorts. Cox proportional hazards regression was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs).
 
 
 
 588 participants with CRC were observed until the date of death or last follow-up (2018), whichever came first. Deficient versus sufficient 25(OH)D concentrations (<30 vs. ≥ 50 nmol/L) were associated with higher overall mortality (HR, 2.06; 95% CI, 1.34 to 3.18) but not with CRC-specific mortality (HR, 1.51; 95% CI, 0.75 to 3.07). The HRs for overall mortality comparing deficient versus sufficient concentrations were 2.43 (95% CI, 1.26 to 4.70) for those with Gc1-1 isoform (rs4588 CC) and 1.63 (95% CI, 0.88 to 3.02) for those with Gc1-2 or Gc2-2 (rs4588 CA or AA) isoforms (P for interaction = 0.54). The HRs for CRC-specific mortality were 1.18 (95% CI, 0.27 to 5.14) for those with Gc1-1 isoform and 1.41 (95% CI, 0.62 to 3.24) for those with Gc1-2 or Gc2-2 isoforms (P for interaction = 0.94).
 
 
 
 In these two 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.
