TY - JOUR
T1 - Novel biomarkers for risk of prostate cancer
T2 - Results from a case-control study
AU - Yang, Li
AU - Gaikwad, Nilesh W.
AU - Meza, Jane
AU - Cavalieri, Ercole L.
AU - Muti, Paola
AU - Trock, Bruce
AU - Rogan, Eleanor G.
PY - 2009/1/1
Y1 - 2009/1/1
N2 - BACKGROUND. Although the estrogens estrone and estradiol are recognized to play very important roles in 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, can 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 adducts 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.
AB - BACKGROUND. Although the estrogens estrone and estradiol are recognized to play very important roles in 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, can 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 adducts 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.
KW - Biomarker
KW - Depurinating estrogen-DNA adducts
KW - Prostate cancer
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U2 - 10.1002/pros.20850
DO - 10.1002/pros.20850
M3 - Article
C2 - 18816637
AN - SCOPUS:58149328544
SN - 0270-4137
VL - 69
SP - 41
EP - 48
JO - Prostate
JF - Prostate
IS - 1
ER -