Abstract B33: Genome-wide methylation analyses reveal racial differences in blood DNA of prostate cancer patients from the North Carolina-Louisiana Prostate Cancer Project (PCaP) cohort.

Epigenetic aberrations occur early in prostate carcinogenesis and contribute to disease progression. African American men experience the highest incidence and mortality from prostate cancer among all groups of men in the US. However, the role of epigenetics in prostate cancer health disparities in African American men has not been investigated thoroughly. Although prostate cancer health disparities are complex phenomena, evidence exists that biological mechanisms contribute to disparity. DNA methylation plays an important role in prostate cancer etiology and progression. Environment-gene interactions may differ between racial groups, in turn leading to variably altered methylomes. Genome-wide investigation of epigenetic variation between African Americans and European Americans may contribute to an understanding of the underlying mechanisms of these health disparities and help identify novel biomarkers of aggressive prostate cancer. We performed a pilot, new generation genome-wide DNA methylation profiling of peripheral blood cell (PBC) DNA from fourteen African Americans and twelve European Americans from the North Carolina-Louisiana Prostate Cancer Project (PCaP) cohort who were matched by age and disease stage. We utilized 450K Illumina methylation array for our studies. Interestingly, we found that African Americans and European Americans are separated into two distinct DNA methylation subgroups using a model-based cluster analysis. Global methylation analysis showed patterns of hypermethylation in African Americans when compared to European Americans, most significantly evident in non-CpG island promoter regions. We then examined gene candidates that were previously implicated in prostate cancer or differentially methylated in normal prostate tissues in African Americans versus European Americans. We identified several genes (e.g., NKX2, RAR-β, and TIMP3) with significant promoter DNA hypermethylation in African Americans when compared to European Americans; this suggests that PBC DNA may in part recapitulate methylation patterns seen in prostate tissue. Our findings demonstrate that racial differences in methylation patterns exist in the blood DNA of prostate cancer patients, which supports the concept that environment-gene interactions might differ among racial and ethnic groups. Furthermore, our findings suggest that future studies should take racial differences into account when searching for blood-based methylation biomarkers. Our ongoing work will explore whether such differences relate to more aggressive disease and poorer prostate cancer outcomes in African Americans when compared to men of European ancestry. (Funded by a grant to AWR from the DoD W81XWH1110308). Citation Format: Anna Woloszynska-Read, Dan Wang, Song Liu, James L. Mohler, Donald L. Trump, Candace S. Johnson. Genome-wide methylation analyses reveal racial differences in blood DNA of prostate cancer patients from the North Carolina-Louisiana Prostate Cancer Project (PCaP) cohort. [abstract]. In: Proceedings of the Fifth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2012 Oct 27-30; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(10 Suppl):Abstract nr B33.