April 8, 2002
MEDIA CONTACT: Vanessa Wasta
PROSTATE CANCER MAY RESULT FROM CHRONIC INFLAMMATION
The earliest stages of prostate cancer may develop in lesions generally associated with chronic inflammation and might be reversible with anti-inflammatory drugs and dietary supplements, new research suggests. Hopkins Kimmel Cancer Center researchers screened several stages of normal and cancerous prostate cells for changes in a key gene, called glutathione S-transferase p (GSTP1), that detoxifies environmental carcinogens and protects against cancer. In prostate cancer, this gene is deactivated through a biochemical process known as hypermethylation. Methylation acts like the safety on a gun, causing a gene to stop working. Too much or "hyper"methylation on the GSTP1 gene shuts off its cancer-preventing properties as the prostate stops producing critical protective enzymes. Hopkins Kimmel Cancer Center researchers looked at GSTP1 hypermethylation in normal and prostate cancers tissue samples as well as in inflammatory prostate lesions known as PIA (proliferative inflammatory atrophy) and PIN (prostate intraepithelial neoplasia). They found GSTP1 methylation in three of 17 (17.6 percent) of PIA lesions, six of ten (60 percent) of high-grade PIN lesions and seven of seven (100 percent) prostate cancers. No GSTP1 methylation was detected in seven samples of normal prostate tissue.
The increasing levels of GSTP1 methylation may show how prostate cancer develops. The starting point may be PIA lesions, which are associated with inflammation and produce high levels of the GSTP1 gene suggesting that the gene has kicked into high gear from some kind of environmental stress. It is in these PIA lesions that researchers believe the first genetic mistakes are made leading to hypermethylation of the GSTP1 gene leaving prostate cells unable to repair damage from carcinogens. With an onslaught of carcinogens from the environment and diet, researchers believe more gene mistakes are made, making PIA lesions progress to PIN lesions, funny-looking cells strongly linked to cancer and considered by some to be pre-cancerous. Investigators will test the prostate cancer preventive effects of anti-inflammatory agents and antioxidant nutrients on PIA lesions in animal models