Free vitamin D (VDR) may be more important than total for bladder cancer – March 2013

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.
Mondul AM, Weinstein SJ, Virtamo J, Albanes D.
Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Department of Health and Human Services, 6120 Executive Boulevard, Suite 320, Rockville, MD, USA. mondulam at mail.nih.gov

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.

PMID: 22990651

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