Circulating Vitamin D–Binding Protein Linked With Decreased RCC Risk

There was a strong inverse association between circulating vitamin D–binding protein (DBP) and the risk for kidney cancer, according to the results of a recent nested case-control study.

The study supports the results of a prior nested case-control study conducted within the Alpha-Tocopherol Beta-Carotene Cancer Prevention (ATBC) study cohort that also found an inverse association between risk for renal cell carcinoma (RCC) and DBP status.

“Further study is required to determine if this association is causal and, if so, through what biological mechanisms,” wrote Alison M. Mondul, PhD, of the University of Michigan, and colleagues, in Cancer Epidemiology Biomarkers and Prevention. “Understanding the latter, and examining the association in diverse populations, could provide new insights into the etiology of kidney and other cancers.”

Mondul and colleagues sought to replicate the results of the ATBC study cohort. Using data from the American Cancer Society Cancer Prevention Study-II Nutrition Cohort, the researchers looked at any association between circulating DBP and RCC risk. The study included 87 patients with RCC who were matched to controls.

Those patients in the highest quartile for circulating DBP were younger, more likely to be female, and more likely to have never smoked. There was a strong inverse association between circulating DBP and risk for RCC (odds ratio [OR], 0.29; 95% CI, 0.09–0.91; P-trend = .02). This trend existed across quartiles, with participants with the highest DBP levels having a markedly decreased risk for RCC (Q1 vs Q2: OR, 0.93; Q1 vs Q3: OR, 0.42; Q1 vs Q4: OR, 0.33).

The researchers noted that results from the ATBC study were among male smokers in Finland, making generalizability to a US population unknown. However, these latest results from a mostly white US population that included women and nonsmokers, “suggest that the inverse association between DBP and kidney cancer is generalizable to these populations.”

No associations between RCC risk and sex, smoking, supplemental vitamin D use, family history of cancer, and body mass index were observed.

As an explanation for why circulating DBP might affect RCC risk, Mondul and colleagues wrote that prior research “suggests that the biologic mechanism through which DBP influences risk of kidney cancer may be unrelated to its canonical role in vitamin D status and transport.”

“DBP has other biologic actions that may play an important role in carcinogenesis and cancer progression, such as it being the parent molecule for DBP-macrophage activating factor, which has been shown to induce apoptosis as well as reduce proliferation and migration of cancer cells in vitro, and inhibit cancer in animal models,” they wrote.

The researchers also suggested that reverse causality was one possible explanation for the results.

“That is, undiagnosed renal malignancies with disrupted physiology would incompletely resorb DBP and lead to decreased concentrations in circulation,” the researchers wrote. “However, our results were essentially identical when cases diagnosed within one year of blood collection were excluded from the analysis, arguing against reverse causality as the basis for our findings.”