Novel Biomarkers for Risk of Prostate Cancer: Results From a Case-Control Study

BACKGROUND. Although the estrogens estrone and estradiol are recognized to play very important roles it) the risk of developing prostate cancer (Pca), the molecular mechanism by which estrogens initiate and/or promote Pca is still unknown. Substantial evidence supports that specific metabolites of estrogens, catechol estrogen quinones, call react with DNA to form depurinating estrogen-DNA adducts. Apurinic sites derived from depurination of these adducts can induce mutations leading to cancer. Once released from DNA, depurinating estrogen-DNA adducts are shed from cells into the bloodstream and excreted in urine. By analyzing profiles of estrogen metabolites, conjugates, and depurinating DNA adducts in urine from men with and without prostate cancer, potential biomarkers of Pca can be detected. The goal of this case-control study was to detect and identify potential biomarkers of Pca. METHODS. Urine samples from fourteen cases, men diagnosed with Pca, and 125 controls, men who had not been diagnosed with Pca, were partially purified by solid phase extraction and analyzed by ultraperformance liquid chromatography/tandem mass spectrometry. The urinary levels of androgens, estrogens, estrogen metabolites, conjugates and depurinating DNA adducts were measured. RESULTS. The ratio of depurinating estrogen-DNA adducts to the sum of the corresponding estrogen metabolites and conjugates was significantly higher in cases (median: 57.34) compared to controls (median: 23.39) (P < 0.001). CONCLUSIONS. This study suggests that depurinating estrogen-DNA ad ducts could serve as potential biomarkers to predict risk of Pca. They also could be useful tools for early clinical diagnosis and development of suitable strategies to prevent Pca. Prostate 69: 41-48, 2009. (C) 2008 Wiley-Liss, Inc.