AACR 2016 Ogunwobi

Non-coding RNA-based biomarker discovery for clinical applications in prostate cancer in males of African ancestry

Men of African ancestry (moAA) have the highest prostate cancer (PCa) incidence and mortality rates compared to other racial groups. Genetic differences, low socioeconomic status, and lack of access to healthcare may play a role in the disparity of prostate cancer among these men. Also, it was recently found that obesity is significantly associated with PCa in moAA, but not in Caucasian men. However, the relationship between these possible risk factors and PCa in moAA is not clearly understood. Therefore, investigating factors that may contribute to PCa incidence and mortality are necessary to address PCa health disparity in moAA. PCa is one of the most heritable common cancers with an estimated 42% of variation attributed to genetic factors. However, deciphering the genetic basis for PCa has been challenging. The most promising results have emerged from recent genome-wide association studies (GWAS) of sporadic PCa, which have identified a number of loci and genetic variants that have been consistently replicated and individually contribute to increase in PCa risk. The 8q24 human chromosomal region is one of the most important susceptibility loci for PCa. Multiple single nucleotide polymorphisms, including rs378854 at the 8q24 human chromosomal region, have been associated with aggressive PCa. The risk allele of rs378854 is associated with increased expression of PVT1 in PCa. Moreover, analysis of human PCa samples have revealed amplification of 8q24 spanning a range that includes the location of PVT1. The PVT1 gene locus encodes six annotated micro RNAs (miRNAs). The role of PVT1 and its encoded miRNAs in PCa is currently unknown.

The goal of this collaborative study by Drs. Ogunwobi (PI) and Camacho-Rivera‎ (collaborator) is to acquire a better understanding of non-coding RNAs (ncRNAs) that are associated with aggressive prostate cancer in moAA. Examining expression of ncRNAs and their molecular targets in men with PCa and determining whether expression of specific ncRNAs differ by race is important in identifying potential biomarkers for PCa outcomes.