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

Clin Cancer Res. 2010 Jul 15;16(14):3539-47. doi: 10.1158/1078-0432.CCR-09-3342. Epub 2010 Jul 6.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • African Americans / genetics*
  • Aged
  • Cell Line, Tumor
  • DNA Methylation*
  • Epithelial Cells / cytology
  • Epithelial Cells / metabolism
  • European Continental Ancestry Group / genetics*
  • Genes*
  • Glutathione S-Transferase pi / genetics
  • Health
  • Homeobox Protein Nkx-2.5
  • Homeodomain Proteins / genetics*
  • Humans
  • Male
  • Middle Aged
  • Osteonectin / genetics
  • Prostate / cytology
  • Prostate / metabolism*
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology
  • Receptors, Androgen / genetics
  • Receptors, Retinoic Acid / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Analysis, DNA
  • Tissue Inhibitor of Metalloproteinase-3 / genetics
  • Transcription Factors / genetics*

Substances

  • Homeobox Protein Nkx-2.5
  • Homeodomain Proteins
  • NKX2-5 protein, human
  • Osteonectin
  • Receptors, Androgen
  • Receptors, Retinoic Acid
  • TIMP3 protein, human
  • Tissue Inhibitor of Metalloproteinase-3
  • Transcription Factors
  • retinoic acid receptor, beta2, human
  • GSTP1 protein, human
  • Glutathione S-Transferase pi