Vitamin D Binding Protein and Risk of Renal Cell Carcinoma in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO).
Int J Cancer. 2019 Oct 29. doi: 10.1002/ijc.32758
Kratzer TB1, Weinstein SJ2, Albanes D2, Mondul AM1.
1 Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI.
2 Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD.
- 5X less risk of Kidney cancer if good ratio of Vitamin D binding protein to circulating vitamin D – Nov 2013
- Vitamin D Binding Protein masks how much Vitamin D gets to tissues – May 2019
- Kidney cancer 22 percent less likely if high vitamin D – meta-analysis Nov 2015
- Classic thought was that Vitamin D level, not VDRP level was the important blood marker for Kidney Cancer
Vitamin D Binding Protein (GC) gene can decrease the bio-available Vitamin D that can get to cells,
- GC is not the only such gene - there are 3 others, all invisible to standard Vitamin D tests
- The bio-available calculation does not notice the effect of GC, CYP27B1, CYP24A1, and VDR
- The actual D getting to the cells is a function of measured D and all 4 genes
- There is >2X increase in 8+ health problems if have poor VDBP (GC)
- It appears that VDBP only blocks oral vitamin D, but not Vitamin D from sun, UV, topical or inhaled (tissue activated)
Vitamin D Binding Protein has a list of health problems
|6 X||Food Allergy|
|4 X, 5X||Kidney Cancer|
|4 X||Poor Response to Oral Vitamin D|
|3 X||Ear infection|
|2 X||Colorectal Cancer|
|2 X||Prostate Cancer -in those with dark skins|
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 non-smokers. 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.
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 (BMI), 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 two 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.
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