Alison Mondul

Ph.D., M.S.P.H.

University of Michigan

Assistant Professor

PLCO (Learn more about this study)

2014-0027

Mar 7, 2014

Serum vitamin D binding protein and risk of renal cell carcinoma

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 vitamin D exposure, or if DBP might independently impact outcomes. Our group recently published a nested case-control analysis within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study cohort of male smokers that examined whether circulating DBP concentration was prospectively associated with renal cell carcinoma risk, and whether it modified the risk association with 25(OH)D. We observed that 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 less than 0.0001), a finding unchanged by adjustment for 25(OH)D. This strong protective association observed between higher circulating DBP concentration and kidney cancer risk suggested a vitamin D-independent influence of DBP on renal carcinogenesis. The present proposal involves a similar nested case-control investigation of renal cell carcinoma aimed at replicating the prior DBP association in the PLCO cohort population that includes women and non-smokers.

1. Examine whether pre-diagnostic serum concentration of vitamin D binding protein (DBP) is associated with risk of renal cell carcinoma in the PLCO cohort.

2. Explore whether the association between DBP and risk of renal cell carcinoma differs by sex or smoking status, or circulating 25(OH)D.