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 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.
Yang
Li
L
Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska 68198-6805, USA.
Gaikwad
Nilesh W
NW
Meza
Jane
J
Cavalieri
Ercole L
EL
Muti
Paola
P
Trock
Bruce
B
Rogan
Eleanor G
EG
D000368:Aged; D000369:Aged, 80 and over; D000728:Androgens / Q000096:biosynthesis / Q000652:urine*; D014408:Biomarkers, Tumor / Q000652:urine*; D016022:Case-Control Studies; D018736:DNA Adducts / Q000096:biosynthesis / Q000652:urine*; D042241:Early Diagnosis; D004967:Estrogens / Q000096:biosynthesis / Q000652:urine*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000453:epidemiology* / Q000652:urine*; D012307:Risk Factors
D000728:Androgens; D014408:Biomarkers, Tumor; D018736:DNA Adducts; D004967:Estrogens