Prostate cancer (PCa) is a common malignancy and a leading cause of cancer deaths among men in the United States. African American (AA) men have both a higher incidence and significantly higher mortality rates than Caucasian (Cau) men. Abundant evidence has accumulated to suggest that epigenetic DNA methylation changes may appear earlier during PCa development than genetic changes, as well as more commonly and consistently. Most studies have emphasized DNA hypermethylation as an important mechanism for inactivation of key regulatory genes in prostate cancers. Thus methylated genes can serve as biomarkers for the detection of cancer from clinical specimens such as tissue biopsies or body fluids. We used pyrosequencing to quantitatively measure methylation status of GSTP1, AR, RAR 2, SPARC, TIMP3 and NKX2-5 in prostate tissue specimen from AA and Cau men. Statistical analysis showed significantly higher methylation in the prostate cancer tissue samples in comparison with matched normal samples. Overall, we observed significant differences (p < 0.05) in the methylation level for all genes (except GSTP1) in the AA samples in comparison to the Cau samples. Furthermore, regression analysis revealed significantly higher methylation for NKX2-5 (p = 0.008) and TIMP3 (p = 0.039) in normal prostate tissue samples from AA in comparison with Cau, and a statistically significant association of methylation with age for NKX2-5 (p = 0.03) in AA in comparison with Cau. In conclusion, we observed higher prevalence of DNA methylation changes in prostate tissue samples from AA in comparison to Cau men. The DNA methylation differences in AA in comparison to Cau men may potentially contribute to racial disparity associated with prostate cancer. Gene specific DNA methylation changes could potentially lead to the identification of “ethnic sensitive” biomarker for PCa detection.

Citation Information: Cancer Epidemiol Biomarkers Prev 2010;19(10 Suppl):B62.