Vitamin D binding protein and risk of renal cell carcinoma in the prostate, lung, colorectal and ovarian cancer screening trial

Abstract

Our group has conducted two previous studies on the association between vitamin D binding protein (DBP) and renal cell carcinoma (RCC), the most common form of kidney cancer, finding strong inverse associations. We undertook the current analysis to replicate our findings in a different study population that included women and nonsmokers. We conducted a nested case-control study in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO). Cases (n = 323) were matched 1:1 to controls on age (AE1 year), race/ethnicity, date of blood collection (AE30 days) and sex. We performed conditional logistic regression to estimate the odds ratios and 95% confidence intervals for the association between quartiles of circulating DBP and risk of RCC. We observed a statistically significant positive association between DBP and RCC that persisted after adjustment for history of diabetes, history of hypertension, family history of renal cancer, body mass index and smoking status (mv-adj Q4 vs. Q1 OR = 4.1, 95% CI = 2.2-7.8; p-trend <0.0001). These findings were similar when we restricted to cases with at least 2 years of follow-up and no major weight loss, suggesting that our findings are not due to reverse causality. In the present study, those with higher serum concentrations of DBP were at increased risk of RCC, in contrast to previously published findings. Further research is necessary to determine the true association between DBP and risk of RCC, and whether different DBP phenotypes may have different associations with risk of RCC.Additional Supporting Information may be found in the online version of this article.

Vitamin D binding protein induces skeletal muscle atrophy and contributes to cancer-associated muscle wasting

“…Increased levels of VDBP have been reported in pathologies often associated with muscle wasting or cachexia, including several tumors [7][8][9][10][11][12] . Since cancer cachexia in humans is often associated with low levels of vitamin D 35 , the increased VDBP could easily lead to the idea of a VDBP-mediated reduction in vitamin D bioavailability.…”

“…Interestingly, proteomic analyses revealed the upregulation of VDBP in biological fluids from patients or animal models affected by pathologies susceptible to progressive muscle wasting or cachexia, including several types of cancer [7][8][9][10][11][12] , chronic kidney disease 13 , diabetes mellitus 14 , multiple sclerosis 15 , Parkinson's disease 16 , and COPD 17 , suggesting a potential role for VDBP in skeletal muscle homeostasis. We specifically hypothesized that VDBP could induce muscle atrophy and participate in cancer-associated muscle wasting.…”