DNA氧化损伤和结直肠癌发病风险的相关研究(英文)

Increased oxidative DNA damage is associated with development of colorectal cancer

目的探讨总抗氧化能力,DNA氧化损伤和单核苷酸多态性(SNP)与结直肠癌的相关风险。方法收集175份人血液样本,其中80例健康对照,67例肠息肉,28例结直肠癌患者。分别采用碱性和经DNA糖基化酶修饰的彗星试验,测定外周血白细胞的直接与DNA氧化损伤,以及血浆中的总抗氧化能力,并采用Applied Biosystems公司的引物系统对单核苷酸多态性进行等位基因鉴别检测。结果结直肠癌患者氧化应激诱导的DNA损伤水平显著高于健康对照组(P<0.05)。肠癌组直接DNA损伤水平也表现出明显升高的趋势(P=0.071)。肠息肉人群总抗氧化能力显著高于对照组。分析肠癌与生活方式(如吸烟和饮酒)关系,肠癌组吸烟率显著高于健康对照组(P<0.01)。分析DNA损伤和修复,代谢和解毒等基因的单核苷酸多态性,hOGG1和GSTM的单核苷酸多态性与结直肠癌之间有一定的相关性。结论高水平的氧化应激诱导的DNA损伤与结直肠癌的发病风险增加相关,是值得进一步研究的潜在的肿瘤生物标志物。

Objective Oxidative DNA damage induced by oxidative stress has been implicated in colorectal cancer risk,based on the measurement of 8OHdG and reactive oxygen metabolites level in the blood.However the direct measurement of oxidative DNA in conelation with colorectal cancer risk has not been reported.The present study was designed to investigate the total antioxidant capacity,oxidative DNA damage and single nucleotide polymorphisms （SNPs） and their associated risk for colorectal cancer （CRC）.Methods Blood samples were collected from 175 subjects including 80 healthy controls,67 patients with polyps,and 28 patients diagnosed with colorectal cancer.Both direct and oxidative DNA damage in peripheral white blood cells （WBCs） were measured using alkaline （direct DNA damage） and formamidopyrimidine DNA glycosylase modified （oxidative DNA damage） Comet assay.Trolax equivalent total antioxidant capacity （TEAC） in plasma was also determined spectrophotometrically.An allelic discrimination assay was utilized to detect variants of a single nucleic acid sequence.Results Oxidative stress induced DNA damage was associated with a significantly higher probability of colorectal cancer compared to healthy controls （P ＜ 0.05）.Direct DNA damage also showed a marginally significant effect on colorectal cancer （P =0.071）.Results from the TEAC assay showed a positive trend on polyps but not on colorectal cancer.Females showed significantly higher probability of developing polyps （P ＜ 0.01）.Further,we analyzed interactions between colorectal cancer and life-style such as smoking and alcohol.We found that there was significantly higher rate of smoking in colorectal group relative to control （health population）.Selected SNPs for oxidative damage,detoxification and DNA repair were examined.The results suggested a correlation between SNPs in hOGG1 and GSTM and colorectal cancer.Conclusion This study suggests that high level of oxidative stress induced DNA damage is associated with increased risk of colorectal cancer,and may be a potential good biomarker.