Examination of Vitamin D Disparities in African American and Caucasian Prostate Cancer Patients and Cells
thesisposted on 21.07.2015, 00:00 by Rachael S. Farhat
African American men have some of the highest rates and poorest outcomes of prostate cancer globally, they are 60% more likely to develop prostate cancer than European American men and 240% more likely to die from the disease. Additionally, African American men have significantly lower levels of vitamin D, in large part due to decreased endogenous production of active vitamin D during exposure to UVB radiation. Vitamin D has been extensively studied and shown to have anti-inflammatory and chemopreventative effects in tissues throughout the body, including the prostate specifically. We hypothesized that in addition to the reduced levels of available vitamin D in African American men, there may be a difference in the effects of vitamin D within the prostate contributing to this disparity. To study this, we used clinical samples as well as in vitro experiments with primary prostate cells. Beyond disparities, we also examined the effects of cross-talk between the two major cell types of the prostate, the stroma and epithelium, and the influence of vitamin D on this interaction. Clinical samples of serum from 46 African American and European American men confirmed that African American men in our cohort had significantly lower levels of vitamin D. SNP analysis of these same patient’s blood quantified percent West African ancestry in patients, but did not find a significant link between percentage West African ancestry and circulating levels of vitamin D. In vitro experiments found a decreased response to active vitamin D treatment in primary stromal prostate cells derived from African American patients compared to cells derived from European Americans. In vitro experiments looking at cross-talk (co-cultures) resulted in luminal differentiation of basal epithelial progenitor cells. However, contrary to our hypothesis we saw no significant difference in differentiation when these cultures were treated with vitamin D. The results of these experiments support the idea that prostatic levels of, and response to vitamin D may play an important role in the disparity of this malignancy.