Early stage prostate cancer in african american males shows down-regulation of trinucleotide repeats

B100

Introduction: It is known that the CAG repeat polymorphism of the androgen receptor gene has been associated with increased risk for prostate cancer and the repeat length correlated with cancer stage and grade at presentation. Short CAG repeat length on the androgen receptor gene is associated with African American (AA) men and possibly with higher stage. Black men tend to have significantly shorter CAG repeats than White American (WM) men. This study proposes a comparison of Prostate Tumor Gene Expression in African American Men to that of White men. The central hypothesis of this study is that unique androgen receptor (AR) molecular signatures exists in prostate tumor specimen obtained from African American Men that are not present in prostate tumor specimen obtained from Caucasian men, due to CAG repeat androgen receptor polymorphisms. Methods: In this pilot project total RNA was isolated from 3+3 PCa tumor specimen along with matched controls from both African American Males and from 3+3 PCa tumor specimen and matched controls from White Males The purified RNA was processed for hybridization to a U133 plus micro-array chip to profile gene expression of these early stage PCa tumors. Normalized micro-array data was analyzed with Genesifter.Net software. Results: A gene expression profile for African American Men showed 95 altered genes (64 up and 31 down-regulated) and a gene expression profile for White Males showed 29 up and 62 down-regulated genes. Down regulation of diacylglycerol kinase gamma 90 was the only gene common to these two profiles. For AA Males down regulation of two tri-nucleotide repeat genes, an androgen-induced proliferation inhibitor and MYC induced nuclear antigen was seen. For White Males, we did not observe any alteration in tri-nucleotide repeats, however, up-regulation of MAPK13 and of presenalin, and down regulation of Cdk5 & Abl enzyme substrate, Caspase1, apoptosis-related cysteine peptidase and protocadherin was observed. Conclusion: Down regulation of genes containing tri-nucleotide repeats may play a role in early stage PCa in AA males but not in White Males. This concept will be discussed at length during the poster discussion.