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Introduction/Study purpose: Vitamin D binding protein (DBP) is the major carrier of vitamin D in circulation. In addition to its role in vitamin D transport, DBP has several other biologic mechanisms that may be relevant to cancer risk including macrophage activation, apoptosis, and angiogenesis. Although previous studies have demonstrated no association between vitamin D and RCC, our group has conducted two previous studies which found strong inverse associations between DBP and RCC. We undertook the current analysis to replicate our findings in a different study population.Methods: 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, date of blood collection (+/- 30 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. In addition to conditioning on the matching factors, multivariable models were further adjusted for history of diabetes or hypertension, family history of renal cancer, body mass index (BMI), and smoking status. Additionally, we performed stratified analyses by sex, family history of renal cancer, BMI, smoking status, and tumor stage at diagnosis.Results: We observed a statistically significant positive association between DBP and RCC that persisted after multivariable adjustment (mv-adj Q4 vs. Q1 OR=3.1, 95% CI=1.8-5.6; p-trend <0.0001). Sensitivity analyses were performed removing matched pairs where the case was diagnosed within 2 years of blood collection or experienced a large weight loss (>40 lbs), with little effect on the overall trend (Q4 vs. Q1 OR=2.5 CI=1.4-4.6 p-trend=<0.0001).Conclusions: In the present study, those with higher serum concentrations of DBP were at increased risk of RCC, which differs from previously-published findings. Further research is necessary to determine the trueassociation between DBP and risk of RCC, and whether different DBP phenotypes via GC variation may have different associations with risk of RCC.Note: This abstract was not presented at the meeting.Citation Format: Tyler B. Kratzer, Alison M. Mondul, Stephanie J. Weinstein, Demetrius Albanes. Vitamin D binding protein and risk of renal cell carcinoma in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 609.