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

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. British Journal of Cancer (2012) 107, 1589-1594. doi:10.1038/bjc.2012.417 www.bjcancer.com Published online 18 September 2012 (C) 2012 Cancer Research UK