The incidence and mortality of prostate cancer (PC) is approximately 2-fold higher among African-Americans as compared to Caucasians and very low in Asian. We hypothesize that inactivation of GSTP1 genes through CpG methylation plays a role in the pathogenesis of PC, and its ability to serve as a diagnostic marker that differs among ethnic groups. GSTP1 promoter hypermethylation and its correlation with clinico-pathological findings were evaluated in 291 PC (Asian = 170; African-American = 44; Caucasian = 77) and 172 benign prostate hypertrophy samples (BPH) (Asian = 96; African-American = 38; Caucasian = 38) using methylation-specific PCR. In PC cells, 5-aza-dC treatment increased expression of GSTP1 mRNA transcripts. The methylation of all CpG sites was found in 191 of 291 PC (65.6%), but only in 34 of 139 BPH (24.5%). The GSTP1 hypermethylation was significantly higher in PC as compared to BPH in each ethnic group (p < 0.0001). Logistic regression analysis (PC vs. BPH) showed that African-Americans had a higher hazard ratio (HR) (13.361) compared to Caucasians (3.829) and Asian (8.603). Chi-square analysis showed correlation of GSTP1 hypermethylation with pathological findings (pT categories and higher Gleason sum) in Asian PC (p < 0.0001) but not in African-Americans and Caucasian PC. Our results suggest that GSTP1 hypermethylation is a sensitive biomarker in African-Americans as compared to that in Caucasians or Asian, and that it strongly influences tumor progression in Asian PC. Ours is the first study investigating GSTP1 methylation differences in PC among African-American, Caucasian and Asian.
Copyright 2005 Wiley-Liss, Inc.