Identification of differentially methylated genes in normal prostate tissues from African American and Caucasian men.

Published

Journal Article

PURPOSE: Aberrant DNA methylation changes are common somatic alterations in prostate carcinogenesis. We examined the methylation status of six genes in prostate tissue specimens from African American (AA) and Caucasian (Cau) males. EXPERIMENTAL DESIGN: We used pyrosequencing to quantitatively measure the methylation status of GSTP1, AR, RARbeta2, SPARC, TIMP3, and NKX2-5. Real-time PCR was used to determine gene expression, and gene reactivation was analyzed by 5-aza-2'-deoxycytidine and/or trichostatin A treatment. RESULTS: Statistical analysis showed significantly higher methylation in the prostate cancer tissue samples in comparison with matched normal samples for GSTP1 (P = 0.0001 for AA; P = 0.0008 for Cau), RARbeta2 (P < 0.001 for AA and Cau), SPARC (P < 0.0001 for AA and Cau), TIMP3 (P < 0.0001 for AA and Cau), and NKX2-5 (P < 0.0001 for AA; P = 0.003 for Cau). Overall, we observed significant differences (P < 0.05) in the methylation level for all genes, except GSTP1, in the AA samples in comparison with 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) after adjusting for race. CONCLUSION: Our findings show higher methylation of several genes in prostate tissue samples from AA in comparison with Cau and may potentially contribute to the racial differences that are observed in prostate cancer pathogenesis.

Full Text

Duke Authors

Cited Authors

  • Kwabi-Addo, B; Wang, S; Chung, W; Jelinek, J; Patierno, SR; Wang, B-D; Andrawis, R; Lee, NH; Apprey, V; Issa, J-P; Ittmann, M

Published Date

  • July 15, 2010

Published In

Volume / Issue

  • 16 / 14

Start / End Page

  • 3539 - 3547

PubMed ID

  • 20606036

Pubmed Central ID

  • 20606036

International Standard Serial Number (ISSN)

  • 1078-0432

Digital Object Identifier (DOI)

  • 10.1158/1078-0432.CCR-09-3342

Language

  • eng

Conference Location

  • United States