Yang Li, Gaikwad Nilesh W, Meza Jane, Cavalieri Ercole L, Muti Paola, Trock Bruce, Rogan Eleanor G
Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska 68198-6805, USA.
Prostate. 2009 Jan 1;69(1):41-8. doi: 10.1002/pros.20850.
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.
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.
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).
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.
尽管雌酮和雌二醇等雌激素在前列腺癌（Pca）发生风险中起着非常重要的作用，但雌激素启动和/或促进Pca的分子机制仍不清楚。大量证据支持雌激素的特定代谢产物儿茶酚雌激素醌可与DNA反应形成脱嘌呤雌激素-DNA加合物。这些加合物脱嘌呤产生的无嘌呤位点可诱导导致癌症的突变。脱嘌呤雌激素-DNA加合物一旦从DNA中释放出来，就会从细胞中脱落进入血液，并随尿液排出。通过分析前列腺癌患者和非前列腺癌患者尿液中雌激素代谢产物、结合物和脱嘌呤DNA加合物的谱图，可以检测到Pca的潜在生物标志物。本病例对照研究的目的是检测和鉴定Pca的潜在生物标志物。
对14例被诊断为Pca的男性患者和125例未被诊断为Pca的男性对照者的尿液样本进行固相萃取部分纯化，并通过超高效液相色谱/串联质谱分析。测量尿液中雄激素、雌激素、雌激素代谢产物、结合物和脱嘌呤DNA加合物的水平。
与对照组（中位数：23.39）相比，病例组（中位数：57.34）中脱嘌呤雌激素-DNA加合物与相应雌激素代谢产物和结合物总和的比值显著更高（P < 0.001）。
本研究表明，脱嘌呤雌激素-DNA加合物可作为预测Pca风险的潜在生物标志物。它们也可能是早期临床诊断和制定预防Pca合适策略的有用工具。
