Age-related DNA methylation changes in normal human prostate tissues.

Area of Science:

• Oncology
• Epigenetics
• Urology

Background:

• Prostate cancer is a significant cause of mortality in aging men, with unclear underlying mechanisms.
• Aberrant promoter CpG island methylation is linked to gene silencing and may contribute to sporadic cancer risk.
• Age-dependent methylation patterns in normal prostate tissue are not well understood.

Purpose of the Study:

• To investigate the extent of gene promoter methylation in pathologically normal human prostate tissue.
• To determine the relationship between gene methylation status and age in normal prostate tissue.
• To compare methylation levels in matched benign and cancerous prostate tissues.

Main Methods:

• Quantitative pyrosequencing analysis of nine CpG islands in normal prostate DNA from 45 organ donors and 45 cystoprostatectomy patients.
• Analysis of 12 matched pairs of benign and prostate cancer tissue DNA.
• Linear regression analysis to correlate methylation levels with age.

Main Results:

• Significant age-dependent increases in promoter methylation were observed for RARbeta2, RASSF1A, GSTP1, NKX2-5, and ESR1 in normal prostate tissue.
• A strong correlation between average methylation across nine CpG loci and age was found (r = 0.6, P < 0.001).
• Prostate cancer tissues exhibited significantly higher methylation levels than matched benign tissues for multiple genes, including RARbeta2, RASSF1A, and GSTP1.

Conclusions:

• Aberrant hypermethylation occurs as a function of age in normal prostate tissues.
• These age-related methylation changes may precede and predispose individuals to prostate cancer.
• Epigenetic alterations in normal prostate tissue are associated with aging and cancer development.