African American men have the highest prostate cancer morbidity and mortality rates than any other racial or ethnic group in the US. Although the overall incidence of and mortality from prostate cancer has been declining in White men since 1991, the decline in African American men lags behind White men. Of particular concern is the growing literature on the disproportionate burden of prostate cancer among other Black men of West African ancestry in the Caribbean Islands, United Kingdom and West Africa. This higher incidence of prostate cancer observed in populations of African descent may be attributed to the fact that these populations share ancestral genetic factors. To better understand the burden of prostate cancer among men of West African Ancestry, we conducted a review of the literature on prostate cancer incidence, prevalence, and mortality in the countries connected by the Transatlantic Slave Trade.

African American Men are 65% more likely to develop prostate cancer and are twice as likely to die of prostate cancer, than are Caucasian American Males. The explanation for this glaring health disparity is still unknown; although a number of different plausible factors have been offered including genetic susceptibility and gene-environment interactions. We favor the hypothesis that altered gene expression plays a major role in the disparity observed in prostate cancer incidence and mortality between African American and Caucasian American Males. To discover genes or gene expression pattern(s) unique to African American or to Caucasian American Males that explain the observed prostate cancer health disparity in African American males, we conducted a micro array pilot project study that used prostate tumors with a Gleason score of 6. We compared gene expression profiling in tumors from African-American Males to prostate tumors in Caucasian American Males. A comparison of case-matched ratios revealed at least 67 statistically significant genes that met filtering criteria of at least +/- 4.0 fold change and p < 0.0001. Gene ontology terms prevalent in African American prostate tumor/normal ratios relative to Caucasian American prostate tumor/normal ratios included interleukins, progesterone signaling, Chromatin-mediated maintenance and myeloid dendritic cell proliferation. Functional in vitro assays are underway to determine roles that selected genes in these onotologies play in contributing to prostate cancer development and health disparity.

Clear-cell renal cell carcinoma (ccRCC) is the most common and aggressive form of all urological cancers, with poor prognosis and high mortality. At late stages, ccRCC is known to be mainly resistant to chemotherapy and radiotherapy. Therefore, it is urgent and necessary to identify biomarkers that can facilitate the early detection of ccRCC in patients. In this study, the levels of transcripts of ccRCC from The Cancer Genome Atlas (TCGA) dataset were used to identify prognostic biomarkers in this disease. Analyzing the data obtained indicated that the KRAB-ZNF protein is significantly suppressed in clear-cell carcinomas. Furthermore, ZNF433 is differentially expressed in ccRCC in a stage- and histological-grade-specific manner. In addition, ZNF433 expression was correlated with metastasis, with greater node involvement associated with lower ZNF433 expression (p < 0.01) and with a more unsatisfactory overall survival outcome (HR, 0.45; 95% CI, 0.33–0.6; p = 8.5 × 10⁻⁸). Since ccRCC is characterized by mutations in proteins that alter epigenetic modifications and /or chromatin remodeling, we examined the expression of ZNF433 transcripts in ccRCC with wildtype and mutated forms of BAP1, KDMC5, MTOR, PBRM1, SETD2, and VHL. Analysis revealed that ZNF433 expression was significantly reduced in ccRCC with mutations in the BAP1, SETD2, and KDM5C genes (p < 0.05). In addition, the ZNF433 promoter region was highly methylated, and hypermethylation was significantly associated with mRNA suppression (p < 2.2 × 10⁻¹⁶). In silico analysis of potential ZNF target genes found that the largest group of target genes are involved in cellular metabolic processes, which incidentally are particularly impaired in ccRCC. It was concluded from this study that gene expression of ZNF433 is associated with cancer progression and poorer prognosis, and that ZNF433 behaves in a manner that suggests that it is a prognostic marker and a possible tumor-suppressor gene in clear-cell renal cell carcinoma.

Background/Aim: Clear-cell renal cell carcinoma (ccRCC) is the most common and aggressive form of all urological cancers, with poor prognosis and high mortality. Despite growing evidence of involvement in carcinogenesis, the role of KRAB-ZFP in ccRCC has not been fully explored. KRAB Zinc finger proteins (KRAB-ZFPs) are the largest family of mammalian transcription regulators. They are differentially expressed in various tissues during cellular development and phenotypic differentiation. Materials and Methods: In this study, the levels of transcripts of ccRCC from The Cancer Genome Atlas (TCGA) dataset were used to identify prognostic biomarkers in this disease. Results: Using bioinformatics techniques, we demonstrate that approximately 60% of KRAB zinc finger proteins located on chromosome 19p13.2 are differentially expressed, with all but two being down-regulated in ccRCC. Moreover, ZNF844, a paralog of ZNF433, was the most down-regulated across all histological grades and pathological stages (p<0.001). In addition, the decrease in ZNF844 expression was associated with poor patient survival (HR=0.41; 95% CI=0.3-0.56; p<0.0001). Gene Set Enrichment Analysis of genes inversely co-expressed with ZNF844 revealed that enriched pathways were consistently related to immune and translation processes (p<0.05, FDR <0.05). Lastly, ZNF844 expression showed moderate, inverse correlation to Helper T-cell (CD4 or Th1) subtype 1 (R=–0.558, p=5.15×10^–39) infiltration and with the exhausted T-cell phenotype (R=–0.37; p=4.1×10^–21). Conclusion: Down-regulation of KRAB-ZFPs at 19p13.2 may represent a signature for ccRCC. Moreover, ZNF844 is a prognostic marker for ccRCC and may serve as a putative immune-related tumor suppressor gene.

This is a short summary of a meeting of the "African-Caribbean Cancer Consortium", jointly organized by the University of Pittsburgh, Department of Epidemiology and the University of Pittsburgh Cancer Institute, held in Montego Bay, Jamaica as a satellite meeting at the Caribbean Health Research Council, 52^nd Annual Council and Scientific meeting on May 4, 2007.