One important method by which cancers can grow in an uncontrolled way is by inactivating key regulatory genes known as "tumor suppressor genes" by epigenetic mechanisms such as DNA methylation. Several genes have been shown to be inactivated by DNA hypermethylation in human prostate cancer. We have found that many of these genes actually undergo DNA methylation as a function of age in normal prostate tissues. Such aberrant DNA methylation in normal prostate cells may in itself be a pathologic event that increases with aging, and this may precede and predispose to full-blown malignancy. The goal of our study is to identify genes that undergo age-related methylation. This would be potentially useful for several reasons. First, it would help in quantifying methylation in the prostate as a function of age and in studying whether such events in genes may predispose aging cells to neoplastic transformation. Second, such a methylation profile would be useful to distinguish benign prostate from cancerous prostate and improve correlations between methylation and prostate tissue pathological features such as stage, grade, and recurrence. Finally, differences in gene methylation profiles from same-age individuals of one ethnic race or of different ethnicity may help in understanding how genetic factors or environmental exposures (or both) contribute to prostate disease. |
