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5X less risk of Kidney cancer if good ratio of Vitamin D binding protein to circulating vitamin D – Nov 2013

Vitamin D binding protein, circulating vitamin D, and risk of renal cell carcinoma

International Journal of Cancer, DOI: 10.1002/ijc.28596
Alison M. Mondul 1, mondulam at mail.nih.gov
Stephanie J. Weinstein 1,
Kristin A. Moy 1,
Satu Männistö 2,
Demetrius Albanes 1
1 Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, MD
2 Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland

Cell culture experiments suggest that vitamin D may inhibit renal carcinogenesis, but human studies of circulating 25-hydroxyvitamin D (25(OH)D), the accepted measure of vitamin D status, and kidney cancer have been null. Limited research has examined the role of circulating vitamin D binding protein (DBP) in the association between 25(OH)D and disease risk, and it is unclear whether free 25(OH)D in circulation is a better measure of effective exposure, or if DBP may independently impact outcomes.

We conducted a nested case-control analysis within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study to examine whether circulating DBP concentration was prospectively associated with risk of renal cell carcinoma, and whether it modified the association with 25(OH)D.

Renal cell carcinoma cases (n=262) were matched 1:1 to controls on age (± 1 year) and date of blood collection (± 30 days). We estimated odds ratios and 95% confidence intervals of renal cell carcinoma risk by quartiles of 25(OH)D, DBP, and the molar ratio of 25(OH)D:DBP, a proxy for free circulating 25(OH)D.

Men with higher DBP concentrations were at significantly decreased risk of kidney cancer (Q4 vs. Q1: OR=0.17, 95% CI=0.08–0.33; p-trend<0.0001), a finding unchanged by adjustment for 25(OH)D.

Although we observed no association with total 25(OH)D, we found slightly increased risk with higher levels of estimated free 25(OH)D (Q4 vs. Q1 of the 25(OH)D:DBP ratio, OR=1.61, 95% CI=0.95–2.73; p-trend=0.09).

The strong protective association observed between higher circulating DBP concentration and kidney cancer risk requires replication but suggests a vitamin D-independent influence of DBP.

Conclusions (from PDF)
In this prospective analysis, men with higher serum concentrations of DBP experienced lower risk of renal cell carcinoma, whereas the 25(OH)D:DBP molar ratio, a proxy for free circulating 25(OH)D, showed a possible positive risk association. Combined, the two findings suggest that the DBP association may reflect a biological mechanism unrelated to vitamin D status. Our findings require confirmation in addi-tional studies, particularly in populations that include womenand nonsmokers. The relationship of circulating bound and free 25(OH)D and DBP with tissue-level availability of25(OH)D also warrants examination, and may help elucidate some of the conflicting results observed in epidemiologic studies of vitamin D and cancer.

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6039 Mondul_et_al-2014-International_Journal_of_Cancer.pdf PDF 2013 admin 11 Oct, 2015 23:04 157.44 Kb 698