Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.
Mutat Res. 2011 Feb 3;719(1-2):41-6. doi: 10.1016/j.mrgentox.2010.11.005. Epub 2010 Nov 21.
The capacity of an individual to process DNA damage is considered a crucial factor in carcinogenesis. The comet assay is a phenotypic measure of the combined effects of sensitivity to a mutagen exposure and repair capacity. In this paper, we evaluate the association of the DNA repair kinetics, as measured by the comet assay, with prostate cancer risk. In a pilot study of 55 men with prostate cancer, 53 men without the disease, and 71 men free of cancer at biopsy, we investigated the association of DNA damage with prostate cancer risk at early (0-15 min) and later (15-45 min) stages following gamma-radiation exposure. Although residual damage within 45 min was the same for all groups (65% of DNA in comet tail disappeared), prostate cancer cases had a slower first phase (38% vs. 41%) and faster second phase (27% vs. 22%) of the repair response compared to controls. When subjects were categorized into quartiles, according to efficiency of repairing DNA damage, high repair-efficiency within the first 15 min after exposure was not associated with prostate cancer risk while higher at the 15-45 min period was associated with increased risk (OR for highest-to-lowest quartiles=3.24, 95% CI=0.98-10.66, p-trend=0.04). Despite limited sample size, our data suggest that DNA repair kinetics marginally differ between prostate cancer cases and controls. This small difference could be associated with differential responses to DNA damage among susceptible individuals.
个体处理 DNA 损伤的能力被认为是致癌作用中的一个关键因素。彗星试验是一种测量对诱变剂暴露的敏感性和修复能力综合效应的表型方法。在本文中，我们评估了彗星试验测量的 DNA 修复动力学与前列腺癌风险之间的相关性。在一项针对 55 名前列腺癌患者、53 名无该病患者和 71 名活检无癌症患者的初步研究中，我们研究了 DNA 损伤与早期（0-15 分钟）和晚期（15-45 分钟）γ 辐射暴露后前列腺癌风险之间的关联。尽管在 45 分钟内的残留损伤在所有组中相同（彗星尾中 65%的 DNA 消失），但与对照组相比，前列腺癌患者的修复反应第一阶段（38%对 41%）较慢，第二阶段（27%对 22%）较快。当根据修复 DNA 损伤的效率将受试者分为四组时，暴露后 15 分钟内的高修复效率与前列腺癌风险无关，而 15-45 分钟期间的高修复效率与风险增加相关（最高至最低四分位数的 OR=3.24，95%CI=0.98-10.66，p 趋势=0.04）。尽管样本量有限，但我们的数据表明，前列腺癌病例和对照组之间的 DNA 修复动力学略有不同。这种微小差异可能与易感性个体对 DNA 损伤的不同反应有关。
