Hypermethylation of GSTP1, CD44, and E-cadherin genes in prostate cancer among US Blacks and Whites.
BACKGROUND
In the US, the incidence and mortality of prostate cancer is about twofold higher among US Blacks compared to Whites, suggesting racial differences in prostate tumor occurrence and aggressiveness. The reason for these racial differences is unknown. Epigenetic events such as promoter-region gene hypermethylation may be influenced by environmental exposures and have been implicated in prostate carcinogenesis (by the silencing of tumor suppressors and other regulatory genes).


METHODS
Using real-time methylation-sensitive PCR, we assessed differences in DNA hypermethylation of GSTP1, CD44, and E-cadherin (three genes thought to be important in the progression of prostate cancer) in archival tumor tissue of black (n = 47) and white men (n = 64).


RESULTS
We found a high prevalence of GSTP1 hypermethylation overall (84%) but no differences by race (89 and 83% in black vs. white men, respectively), tumor stage, or grade. Although CD44 hypermethylation was less prevalent overall (found in 32% of tumors), we observed a 1.7-fold higher frequency among black men (43 vs. 25% in black vs. white men, P = 0.05) and a correlation with tumor grade (CD44 was hypermethylated in 10, 42, and 52% of well, moderate, and poorly differentiated tumors, respectively, P = 0.003) but not disease stage. The E-cadherin gene was not hypermethylated in any of the tumors. In summary, of the three genes examined, only CD44 hypermethylation differed by race and correlated with tumor grade, independent of race.


CONCLUSIONS
These preliminary findings suggest that differences in gene promoter hypermethylation may potentially underlie racial differences in prostate cancer pathogenesis and should be explored in larger studies.
Woodson
Karen
K
Cancer Prevention Studies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892, USA. kw114@nih.gov
Hayes
Richard
R
Wideroff
Louise
L
Villaruz
Liza
L
Tangrea
Joseph
J
D000368:Aged; D044383:Black People; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D002277:Carcinoma / Q000235:genetics*; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics* / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods; D011471:Prostatic Neoplasms / Q000235:genetics*; D044465:White People
D015820:Cadherins; D004273:DNA, Neoplasm; D018960:Hyaluronan Receptors; D007527:Isoenzymes; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase