Cancer health disparities represent a major public health concern in the United States. Even when socioeconomic factors are accounted for, minority populations have higher overall incidence rates and worse outcomes than the overall population. Prostate cancer is one of such disease with higher incidence and death rate in African American (AA) men than Caucasians. Although socioeconomic factors may be blamed to a certain extent, it is being appreciated that the differences in tumor biology make AA men more prone to the aggressive prostate cancer. Therefore, understanding the impact of biological variability in prostate cancer is vital to reduce the observed cancer outcome gaps between AA men and Caucasians. Our goal is to determine the role of macrophage inhibitory cytokine (MIC-1) as a biological factor that play a critical role in prostate tumor biology leading to cancer heath disparities. MIC-1 has drawn significant attention due to its increased association with the development and progression of prostate cancer, and increasing serum MIC-1 levels correlates with the presence of bone metastasis. Preliminary data from our laboratory clearly demonstrate that serum MIC-1 in prostate cancer patients is significantly higher in AA men than Caucasians. We hypothesize that increased level of MIC-1 in prostate tumor microenvironment of African American men contributes to an increase in prostate cancer health disparity. To date the role of MIC-1 to differentiate the aggressive prostate cancer among AA men and Caucasians has not been investigated. To test the above hypothesis, our specific Aims are: 1) To determine the clinical significance of MIC-1 in prostate cancer health disparity among African American men and Caucasians;and 2) To determine the mechanism of MIC-1 in immune surveillance leading to prostate cancer disparity using mouse models. Using the skills of multidisciplinary team of investigators, we will measure serum MIC-1 levels in prostate cancer patients with recurrent metastasis, and newly diagnosed prostate cancer. We will also analyze the stromal and epithelial expression of MIC-1 in archival specimens of human prostate tumor tissues from AA men and Caucasians. We will determine the mechanistic role of MIC-1 regulating aggressive prostate cancer by analyzing the nature of infiltrating lymphocytes using immuno- competent mouse models. Clearly, the serum MIC-1 levels differ in AA men and Caucasians with prostate cancer. This will have a significant impact to establish the biological role of MIC-1 contributing o prostate cancer health disparity for its subsequent translation into clinics to reduce the sufferin of African American men with prostate cancer using improved therapeutic treatment modalities.
Given the facts of a significant racial disparity in prostate cancer among African American (AA) men and Caucasians, there is an utmost need to understand the prostate tumor biology. Apart from socioeconomic factors, AA men clearly differ from Caucasians on a number of accounts, including genetic predisposition, which favors for high incidence and mortality rate for prostate cancer development. Preliminary data from our laboratory clearly demonstrate that serum MIC-1 (macrophage inhibitory cytokine) in prostate cancer patients was significantly higher in AA men than Caucasians. Therefore, we propose to determine that MIC-1 plays a vital role in regulating prostate tumor biology resulting in racial disparity. Clinical validation of MIC-1 will help to develop better strategies for prostate cancer diagnosis and treatment to reduce the observed cancer outcome gaps between African American men and Caucasians.
|Karan, Dev; Dubey, Seema (2016) From Inflammation to Prostate Cancer: The Role of Inflammasomes. Adv Urol 2016:3140372|
|Dubey, Seema; Vanveldhuizen, Peter; Holzbeierlein, Jeffrey et al. (2012) Inflammation-associated regulation of the macrophage inhibitory cytokine (MIC-1) gene in prostate cancer. Oncol Lett 3:1166-1170|