Global Epigenetic Changes May Underlie Ethnic Differences and susceptibility to Prostate Cancer
Annual rept. 26 Aug 2011-25 Aug 2012
HOWARD UNIV WASHINGTON DC
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The incidence and mortality of prostate cancer PCa is approximately 2 fold higher in African American AA than in European-American EA men. This disparity is believed to be a complex combination of environment, socioeconomic factors and genetics. The purpose of the present study is to study genome wide DNA methylation changes in prostate biospecimens from AA and EA men in order to elucidating the epigenetic DNA methylation changes associated with prostate cancer disparity and identify novel biomarkers for early disease detection. RESULTS In our preliminary genome-wide methylation studies, we examined the methylation status of Infunium 450K 484,968 CpG sites that corresponds to 21,221 genes in microarray illumina analysis. In all, we selected 25 promoter associated novel CpG sites that were differentially methylated in correlation with prostate cancer progression from benign to HGPIN to prostate cancer FDR adjusted p- value 0.05 b value 0.2 fold change 1.5. Several novel genes demonstrated significant difference in methylation patterns in AA versus EA prostate cancer cell lines. Conclusion Our on-going genome-wide methylation approach based on the methyl-binding domain of MBD2 qMBD-seq coupled with newly developed computational methods has the advantage that we can now obtain genome-wide methylation data without bias to specific regions in comparison with other independent methodologies such as the Infunium 450K array and this will improve the quantitative determination of DNA methylation status across sample groups e.g. AA versus EA samples. Concerted efforts to accurately study genome wide DNA methylation changes in prostate biospecimens from AA in comparison to EA men is needed in order to fully understand the molecular mechanisms underlying PCa disparity if genome knowledge-based perspective can be used to eliminate PCa health disparity.
- Anatomy and Physiology
- Medicine and Medical Research