In what researchers said is the second study of its kind, it was determined that circulating vitamin D binding protein (DBP) is inversely associated with the risk of kidney cancer.1 The findings, which were published in Cancer Epidemiology, Biomarkers & Prevention, support previous data that demonstrated that a higher DBP was linked to a decreased risk of developing renal cell carcinoma (RCC).2

The current case-control study — which was nested in the American Cancer Society Cancer Prevention Study-II (CPS-II) Nutrition Cohort that began in 1992 — sought to prospectively confirm the suspected link between DBP concentration and the risk of renal cell carcinoma. It included 39,371 individuals who provided a blood sample and were free of cancer at the time of blood collection; 87 of these individuals were determined to have a primary diagnosis of RCC prior to June 30, 2009. A diagnosis of RCC was collected by way of self-reported questionnaires and confirmed through the review of medical records and the National Death Index.

The investigators found that a higher level of serum DBP concentration was inversely associated with renal cell carcinoma risk (P-trend = .02). Individuals with the highest levels of DBP were found to be younger, more likely to be female, had a lower BMI, and were more likely to be nonsmokers.

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Alison Mondul, PhD, MSPH, assistant professor of epidemiology at the University of Michigan in Ann Arbor, and an author of the study, told Cancer Therapy Advisor that based on what is known so far, vitamin D itself doesn’t have a big effect on the risk of developing kidney cancer. But, DBP can help investigators estimate the proportion of vitamin D that is free versus bound in circulation. “Studies of other things in the body, like sex hormones, have suggested that only free, unbound hormones can have an effect. Based on a previous study, free vitamin D, just like total vitamin D, was also not associated with risk of RCC.”

Dr Mondul added that there were no strong associations seen with DBP as it related to prostate cancer, colorectal cancer, lung cancer, and bladder cancer. “Thus far, the association really does seem to be different for renal than for other sites. This is a relatively new area, however, and we need to do more [research] to fully understand this association.”

Although previous studies have concluded that there was no strong link between circulating 15(OH)D and kidney cancer, and DBP did not appear to influence the risk association with 25(OH)D, the researchers hypothesized “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.”2 Simply put, DBP may influence carcinogenesis through a mechanism outside of its role of delivering vitamin D metabolites to various organs.

Limitations of the study included low statistical power to detect the effect of lifestyle factors and the bulk of cases examined were of patients with European ancestry. “Given that there is an existing racial disparity in kidney cancer incidence in the [United States] with higher rates among black men compared to white men, further study in non-white populations is warranted.”

In addition, the sample size of the study was fairly small, but the authors said this was expected, as RCC is a relatively rare cancer.


  1. Mondul AM, Weinstein SJ, Parisi D, et al. Vitamin D binding protein and risk of renal cell carcinoma in the Cancer Prevention Study-II Cohort [published online July 20, 2018]. Cancer Epidemiol Biomarkers Prev. doi: 10.1158/1055-9965.EPI-18-0263
  2. Tagliabue E, Raimondi S, Gandini S. Meta-analysis of vitamin D-binding protein and cancer risk. Cancer Epidemiol Biomarkers Prev. 2015;24(11):1758-1765. doi: 10.1158/1055-9965.EPI-15-0262