Abstract
Background. Prostate cancer (PCa) is the most common non-skin cancer in men. Risk factors include age, African race, and family history. Methylation has been associated with gene regulation and prostate cancer development. Here we compared the global methylation profiles in normal and malignant tissues of African American (AA) and Caucasian patients with PCa.
Methods. DNA was extracted, treated with sodium bisulfite and hybridized to chips interrogating the status of more than 27,000 CpG sites in 14,000 genes. The β value (methylation fraction) was compared separately between normal and malignant tissues from AA and Caucasians to identify those CpG with at least 2-fold change (tumor/normal). The genes containing those differentially methylated CpG were analyzed in MetaCore to find cellular processes associated with either AA or Caucasians, or both.
Results. Two hundred fifteen (215) CpG sites were associated with AA, 42 CpG sites were found exclusively in Caucasians, and 47 were found in both ethnic groups. Pathway and network analyses showed that the most prominent cellular processes associated with the genes harboring those significant CpG sites in AA are involved in tissue remodeling / wound repair (p=2.98 x 10-5) and neurogenesis (1.068 x 10-5), while neurotransmission (p=0.006) and regulation of proliferation (p=0.0004) were the most prominent in Caucasians. Calcium signaling and platelet aggregation were the most prominent common processes to both ethnic groups.
Conclusion. Divergent pathways may exist in PCA in AA and Caucasians suggesting different targets for treatment
Citation Format: Shahriar Koochekpour, Jovanny Zabaleta. Differential profiles of methylation in African American and Caucasian men diagnosed with prostate cancer. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr B24. doi:10.1158/1538-7755.DISP13-B24
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