Correlating blood-based DNA methylation markers and prostate cancer risk in African-American men.

Emmanuel Moses-Fynn,Yasmine Kanaan,Desta Beyene,Robert Copeland,Bernard Kwabi-Addo,Wei Tang,Victor Apprey,Chih-Pin Chuu

doi:10.1371/journal.pone.0203322

Abstract

The objective of this work was to investigate the clinical significance of promoter gene DNA methylation changes in whole blood from African-American (AA) men with prostate cancer (PCa). We used high throughput pyrosequencing analysis to quantify percentage DNA methylation levels in a panel of 8 genes (RARβ2, TIMP3, SPARC, CDH13, HIN1, LINE1, CYB5R2 and DRD2) in blood DNA obtained from PCa and non-cancerous controls cases. Correlations of methylation status and various clinicopathological features were evaluated. Six genes tested achieved significant difference in DNA methylation levels between the PCa compared to control cases (P < 0.05). The TIMP3 loci demonstrated significant correlation of DNA methylation with age for all cases analyzed (p < 0.05). We observed an inverse correlation between CDH13 methylation (p = 0.045; r = -0.21) and serum vitamin D level whereas TIMP3 methylation (p = 0.021; r = -0.24) and DRD2 methylation (p = 0.056; r = -0.201) showed inverse correlation with supplementary vitamin D in the cancer cases. We also observed a direct correlation between methylation of RARβ2 (p = 0.0036; r = 0.293) and SPARC (p = 0.0134; r = 0.20) loci with PSA level in the controls but not the cancer cases. In addition, alcohol cases significantly correlated with higher RARβ2 methylation (p = 0.0314) in comparison with non-alcohol cases. Furthermore, we observed an inverse correlation of DRD2 methylation (p = 0.0349; r = -0.343) and Gleason score. Our data suggests that promoter methylation occurred more frequently in the blood of AA PCa and is associated with various clinicopathological features in AA men with PCa.

Highlights

The incidence and mortality rate of prostate cancer (PCa) is higher for African-American (AA) men than any other US racial and ethnic groups [1,2]
The mean age is 58.6 (± 9.558) for controls and 68.5 (± 9.09) for cases, indicating that the average age of cases were higher than control; and an age over 60 years was significantly associated with PCa risk when compared with the control individuals (OR = 8.06; 95% Cl = 2.44–26.58, p = 0.0006)
We analyzed a total panel of 8 genes: RARβ2, TIMP3, SPARC, and CYB5R2 that we have previously demonstrated to be most differentially hypermethylated in PCa in AA and EA men [16] and LINE1, HIN1 and CDH13 that we have shown to be most differential hypermethylated in Breast cancers from AA and EA women [24]

Summary

Introduction

The incidence and mortality rate of prostate cancer (PCa) is higher for African-American (AA) men than any other US racial and ethnic groups [1,2]. Supporting reports from autopsy data suggests higher incidence of high grade prostate intraepithelial neoplasia and PCa in AA men when compared to age-adjusted EA men. The disparity of PCa incidence and mortality rates is believed to be a complex integration of socioeconomic factors, environment and biology [6]. While some of the PCa disparity can be attributed to environmental and/or socioeconomic factors, a number of studies points to a higher mortality rate for AA men with PCa even after adjustment for these factors [6]. Biological differences may account for a significant proportion of PCa disparity in AA men in comparison to EA men [6]

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