e16046 Background: The current screening method for prostate cancer (PC), which is based on prostate specific antigen (PSA) level lacks specificity and sensitivity. Previous studies have reported that increased levels of free circulating DNA (fcDNA) and hypermethylation of genes are associated with several cancers. In this study we evaluated the use of fcDNA level and aberrant promoter methylation of 4 genes in serum as biomarkers for PC. Methods: 89 PC patients, 59 with prostatitis (PT) and 104 with benign prostatic hyperplasia (BPH) were enrolled. Serum DNA was analyzed for methylation of GSTPi, RARB, RASSF1A and ECAD by methylation-specific PCR. FcDNA level was analyzed by quantitative PCR. We examined the effect of methylation and fcDNA on PC risk by fitting two logistic regression models, one comparing PC vs BPH and PT vs BPH and the other comparing PC vs PT+BPH. Models were adjusted for age, race, and log2PSA, and tested for variation in effect of methylation by race. Similar analyses assessed the effect of fcDNA as continuous variable, after log2 transformation, and as dichotomous variable with cutpoint near the upper quartile for BPH controls. Results: When adjusted for age and log2PSA, positive GSTPi methylation was associated with increased risk of PC in whites (OR = 6.11, p < 0.001, PC vs BPH; OR = 3.93, p = 0.001, PC vs BPH + PT). Methylation of RARB was associated with PT independent of race (OR = 2.85, p = 0.032, PT vs BPH). Patients with fcDNA ≥180ng/ml were at twice the risk of PC compared to those with levels <180ng/ml, and this result did not vary by race. Models including both GSTPi and fcDNA confirmed the independent effect of these two factors in whites (high fcDNA OR = 3.77, p = 0.002, positive GSTPi methylation OR = 5.41, p < 0.001, PC v. BPH + PT). Although high fcDNA also increased risk of PC in blacks, the effect was not statistically significant (OR = 1.91, p = 0.189, PC vs BPH + PT). Conclusions: Our results suggest that aberrant promoter methylation of GSTPi in serum is a potential biomarker for prostate cancer in whites. Level of fcDNA in serum also appears to be an independent diagnostic marker in whites. No significant financial relationships to disclose.
Aberrant Promoter Methylation of Protocadherin8 (PCDH8) in Serum is a Potential Prognostic Marker for Low Gleason Score Prostate Cancer