Department of Urologic Surgery, Vanderbilt University Medical Center, Nashville, Tennessee 37203, USA.
J Urol. 2011 Jun;185(6):2102-7. doi: 10.1016/j.juro.2011.02.020. Epub 2011 Apr 15.
Oxidative stress is implicated in prostate cancer by several lines of evidence. We studied the relationship between the level of F2-isoprostanes, a validated biomarker of oxidative stress, and prostate cancer and high grade prostatic intraepithelial neoplasia.
This case-control analysis within the Nashville Men's Health Study included men recruited at prostate biopsy. Body morphometrics, health history and urine were collected from more than 2,000 men before biopsy. F2-isoprostanes were measured by gas chromatography/mass spectrometry within an age matched sample of Nashville Men's Health Study participants that included 140 patients with high grade prostatic intraepithelial neoplasia, 160 biopsy negative controls and 200 prostate cancer cases. Multivariable linear and logistic regression was used to determine the associations between F2-isoprostane level, and high grade prostatic intraepithelial neoplasia and prostate cancer.
Mean patient age was 66.9 years (SD 7.2) and 10.1% were nonwhite. Adjusted geometric mean F2-isoprostane levels were higher in patients with prostate cancer (1.82, 95% CI 1.66-2.00) or high grade prostatic intraepithelial neoplasia (1.82, 95% CI 1.68-1.96) than in controls (1.63, 95% CI 1.49-1.78, p <0.001), but were similar across Gleason scores (p = 0.511). The adjusted odds of high grade prostatic intraepithelial neoplasia and prostate cancer increased with increasing F2-isoprostane quartile (p-trend = 0.015 and 0.047, respectively) and the highest F2-isoprostane quartile was associated with significantly increased odds of prostate cancer (OR 2.44, 95% CI 1.17-5.09, p = 0.017).
Pre-diagnosis urine F2-isoprostane level is increased in men with high grade prostatic intraepithelial neoplasia or prostate cancer, suggesting urinary F2-isoprostane provides a biomarker for the role for oxidative stress in prostate carcinogenesis. F2-isoprostanes may also serve to estimate the efficacy of interventions targeting oxidative stress mechanisms in prostate cancer prevention or treatment.
氧化应激是几种证据表明与前列腺癌有关。我们研究了 F2-异前列腺素水平与前列腺癌和高级别前列腺上皮内瘤变之间的关系，F2-异前列腺素是一种已验证的氧化应激生物标志物。
本研究是纳什维尔男性健康研究中的病例对照分析，包括在前列腺活检前招募的男性。超过 2000 名男性在活检前采集了身体形态、健康史和尿液。在年龄匹配的纳什维尔男性健康研究参与者样本中，通过气相色谱/质谱法测量了 F2-异前列腺素，该样本包括 140 名高级别前列腺上皮内瘤变患者、160 名活检阴性对照者和 200 名前列腺癌病例。多变量线性和逻辑回归用于确定 F2-异前列腺素水平与高级别前列腺上皮内瘤变和前列腺癌之间的关系。
患者平均年龄为 66.9 岁（标准差 7.2），10.1%为非白人。与对照组（1.63，95%置信区间 1.49-1.78，p<0.001）相比，前列腺癌（1.82，95%置信区间 1.66-2.00）或高级别前列腺上皮内瘤变（1.82，95%置信区间 1.68-1.96）患者的调整后几何均数 F2-异前列腺素水平更高，但在 Gleason 评分方面无差异（p=0.511）。F2-异前列腺素四分位数越高，高级别前列腺上皮内瘤变和前列腺癌的调整后比值比（OR）越高（p-trend=0.015 和 0.047），F2-异前列腺素最高四分位数与前列腺癌的OR 显著升高（OR 2.44，95%置信区间 1.17-5.09，p=0.017）。
高级别前列腺上皮内瘤变或前列腺癌患者的预诊断尿液 F2-异前列腺素水平升高，提示尿液 F2-异前列腺素为氧化应激在前列腺癌发生中的作用提供了生物标志物。F2-异前列腺素也可能用于估计针对氧化应激机制的干预措施在前列腺癌预防或治疗中的效果。
