Serum Vitamin D, Vitamin D Binding Protein, and Risk of Colorectal Cancer

PLoS One. 2014 Jul 18;9(7):e102966. doi: 10.1371/journal.pone.0102966. eCollection 2014.


Background: We previously reported a positive association between serum 25-hydroxyvitamin D (25(OH)D) and colorectal cancer risk. To further elucidate this association, we examined the molar ratio of 25(OH)D to vitamin D binding protein (DBP), the primary 25(OH)D transport protein, and whether DBP modified the association between 25(OH)D and colorectal cancer risk.

Methods: In a nested case-control study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, controls were 1∶1 matched to 416 colorectal cancer cases based on age and date of blood collection. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CI) for quartiles of 25(OH)D, DBP, and the molar ratio of 25(OH)D:DBP, a proxy for free, unbound circulating 25(OH)D.

Results: Comparing highest to lowest quartiles, DBP was not associated with colorectal cancer risk (OR = 0.91; 95% CI: 0.58, 1.42, p for trend = 0.58); however, a positive risk association was observed for the molar ratio of 25(OH)D:DBP (OR = 1.44; 95% CI: 0.92, 2.26, p for trend = 0.04). In stratified analyses, the positive association between 25(OH)D and colorectal cancer was stronger among men with DBP levels above the median (OR = 1.89; 95% CI: 1.07, 3.36, p for trend = 0.01) than below the median (OR = 1.20; 95% CI: 0.68, 2.12, p for trend = 0.87), although the interaction was not statistically significant (p for interaction = 0.24).

Conclusion: Circulating DBP may influence the association between 25(OH)D and colorectal cancer in male smokers, with the suggestion of a stronger positive association in men with higher DBP concentrations. This finding should be examined in other populations, especially those that include women and non-smokers.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Case-Control Studies
  • Colorectal Neoplasms / blood*
  • Colorectal Neoplasms / etiology*
  • Double-Blind Method
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Odds Ratio
  • Risk
  • Risk Factors
  • Vitamin D / analogs & derivatives
  • Vitamin D / blood*
  • Vitamin D / metabolism
  • Vitamin D-Binding Protein / blood*
  • Vitamin D-Binding Protein / metabolism
  • alpha-Tocopherol / metabolism
  • beta Carotene / metabolism


  • Vitamin D-Binding Protein
  • beta Carotene
  • Vitamin D
  • 25-hydroxyvitamin D
  • alpha-Tocopherol