Influence of vitamin D binding protein on the association between circulating vitamin D and risk of bladder cancer

Br J Cancer. 2012 Oct 23;107(9):1589-94. doi: 10.1038/bjc.2012.417. Epub 2012 Sep 18.


Background: There is little research investigating the role of vitamin D binding protein (DBP) in the association between 25-hydroxyvitamin D (25(OH)D) and disease risk.

Methods: Within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, 250 bladder cancer cases were randomly sampled and matched 1:1 to controls on age and date of blood collection. Odds ratios (OR) and 95% confidence intervals (CI) of bladder cancer were estimated by quartiles of DBP (measured by ELISA), 25(OH)D and the molar ratio of 25(OH)D:DBP, a proxy for free circulating 25(OH)D. Analyses were also conducted stratifying 25(OH)D by DBP (median split) and vice versa.

Results: We found no direct association between circulating DBP levels and bladder cancer risk (P-trend=0.83). The inverse association between 25(OH)D and bladder cancer risk was unchanged after adjustment for DBP (Q4 vs Q1 OR=0.61, 95% CI=0.36-1.05; P-trend=0.04), and was stronger among men with lower DBP (low DBP: 25(OH)D Q4 vs Q1 OR=0.47, 95% CI=0.23-1.00; high DBP: 25(OH)D Q4 vs Q1 OR=0.83, 95% CI=0.40-1.75; P for interaction=0.11).

Conclusion: Our findings provide additional support for an aetiologic role for vitamin D in bladder cancer and suggest that free, rather than total, circulating vitamin D may be a more relevant exposure when examining bladder and, perhaps, other cancers.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticarcinogenic Agents / therapeutic use
  • Case-Control Studies
  • Double-Blind Method
  • Humans
  • Male
  • Middle Aged
  • Prospective Studies
  • Risk Factors
  • Urinary Bladder Neoplasms / blood*
  • Urinary Bladder Neoplasms / prevention & control
  • Vitamin D / analogs & derivatives*
  • Vitamin D / blood
  • Vitamin D-Binding Protein / blood*
  • alpha-Tocopherol / therapeutic use
  • beta Carotene / therapeutic use


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