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

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 (1 year), race/ethnicity, date of blood collection (30days) 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 2years 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. What's new? Vitamin D binding protein (DBP) plays several biological functions of potential relevance to cancer risk. However, its role in renal cell carcinoma (RCC) remains unclear. This prospective, relatively large nested case-control study revealed a statistically significant positive association between DBP and RCC that persisted after adjustment for diabetes, hypertension, renal cancer family history, body mass index, and smoking status. This is a novel finding that runs in opposition to previous cohort studies investigating the association between DBP and risk of RCC, calling for further research on the true association between DBP and RCC and the potential roles of different DBP phenotypes.