Prostate cancer is a leading cause of cancer death among men in the United States. The current method used for the screening for prostate cancer, the prostate-specific antigen (PSA) test, has poor specificity and sensitivity. This has lead to the search for new biomarkers that can improve the prostate cancer screening, either by themselves or in combination with established markers. Epigenetic modifications, believed to occur early during tumorgenesis are one of the new measurements that could aid in improving prostate cancer screening. We conducted a case-control study to determine the association of promoter methylation of p16 INK4a and GSTP1 and prostate cancer risk. Twenty seven histologically confirmed prostate cancer patients were matched by age and ethnicity to twenty four controls. DNA was extracted from plasma, and percentage of DNA methylation was determined by pyrosequencing. We found that methylation levels were consistently higher in cases than in controls, but this difference was not statistically significant (p16 INK4a OR (95%CI)=2.38 (0.75-7.50); GSTP1 OR (95%CI)=2.57 (0.79-8.40). Methylation levels in these regions were also investigated in tumor and normal adjacent tissue samples from cases. Promoter regions of these genes are hypermethylated in prostatic tumors (7.2% for p16INK4a and 95.8% for GSTP1). Hypermethylation of both regions is statistically significantly associated with tumor status with OR p16INK4a =5.0, 95%CI: 1.3-19.1 and ORGSTP1=22.9, 95%CI: 2.7-198.6, respectively. The correlations of GSTP1 and p16INK4a methylation levels in matched tissue and plasma samples were also determined. Pearson's correlation coefficient was 0.46 for GSTP1 methylation when comparing tumor tissue and plasma (p=0.037). However, the tissue-plasma correlation for p16INK4a methylation levels was not statistically significant. Our samples size is small, but our results are encouraging suggesting that plasma DNA methylation levels at the promoter regions of p16INK4a and GSTP1 are relevant in the etiology of prostate cancer and may be useful as markers of the onset of prostate cancer.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4936.