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

Abstract

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-trend0.83). The inverse association between 25(OH)D and bladder cancer risk was unchanged after adjustment for DBP (Q4 vs Q1 OR0.61, 95% CI0.361.05; P-trend0.04), and was stronger among men with lower DBP (low DBP: 25(OH)D Q4 vs Q1 OR0.47, 95% CI0.231.00; high DBP: 25(OH)D Q4 vs Q1 OR0.83, 95% CI0.401.75; P for interaction0.11). 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. © 2012 Cancer Research UK All rights reserved.