OGG1 expression and OGG1 Ser326Cys polymorphism and risk of lung cancer in a prospective study
OGG1 expression and OGG1 Ser326Cys polymorphism and risk of lung cancer in a prospective study
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DOI：
10.1016/j.mrfmmm.2007.11.002
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发表时间：
2008-03-01
影响因子：
2.3
通讯作者：
Vogel, Ulla
中科院分区：
文献类型：
--
作者：
Hatt, Lotte;Loft, Steffen;Vogel, Ulla
DNA氧化损伤被认为与肺癌的发生有关。8-OxodG是一种在DNA中诱导的诱变和丰富的氧化修饰。OGG1， NEIL1和MUTYH都参与8- oxodg衍生突变的修复和预防，并可能在氧化应激下上调。在一些研究中，多态性OGG1 Ser326Cys与肺癌的风险有关。在57,053名丹麦人的人群队列中，我们研究了灰褐色外套材料中OGG1、NEIL1、MUTYH和NUDT mRNA水平与随后肺癌风险之间的关系。260例肺癌患者被确诊，263人的亚队列在性别、年龄和吸烟时间上进行了匹配。我们发现健康个体的OGG1 mRNA水平与随后患肺癌的风险无关。然而，OGG1 Cys326/Cys326基因型受试者的OGG1 mRNA表达水平高于野生型等位基因携带者。纯合子Cys326携带者OGG1 mRNA水平翻倍的发生率比（IRR）为1.51 (95% CI: 1.09 ~ 2.08)，基因型与mRNA水平的交互作用有统计学意义。在不吸烟者中，每增加一倍OGG1 nrRNA水平的IRR为4.29(1.09-16.9)，而在吸烟者中没有发现。此外，我们发现OGG1 mRNA的表达与尿中8-oxodG的排泄量呈正相关（RS = 0.18; p < 0.005）。由于低且不可靠的表达水平，NUDT1 mRNA水平被省略。结果表明，OGG1 mRNA水平应被视为暴露于氧化应激诱导DNA的生物标志物，而不是先天DNA修复能力的标志物。(c) 2007 Elsevier B.V.版权所有
Oxidative DNA damage is believed to be implicated in lung carcinogenesis. 8-OxodG is a mutagenic and abundant oxidative modification induced in DNA. OGG1, NEIL1 and MUTYH are all involved in the repair and prevention of 8-oxodG-derived mutations and may be up-regulated by oxidative stress. The polymorphism OGG1 Ser326Cys has in some studies been associated with risk of lung cancer.In a population-based cohort of 57,053 Danes, we examined associations between mRNA levels of OGG1, NEIL1, MUTYH and NUDT in buffy coat material and subsequent lung cancer risk. 260 cases with lung cancer were identified and a sub-cohort of 263 individuals was matched on sex, age and smoking duration.We found that OGG1 mRNA levels in healthy individuals were not associated with risk of subsequent getting lung cancer. However, subjects with the OGG1 Cys326/Cys326 genotype had a higher expression level of OGG1 mRNA than wildtype-allele carriers. For homozygous Cys326 carriers, the incidence rate ratio (IRR) was 1.51 (95% CI: 1.09-2.08) for a doubling of the OGG1 mRNA level and there was a statistically significant interaction between the genotype and mRNA level. Among never-smokers, the IRR was 4.29 (1.09-16.9) per doubling of the OGG1 nrRNA level, which was not found among smokers. Furthermore, we found a positive correlation between OGG1 mRNA expression and urinary excretion of 8-oxodG (RS = 0.18; p < 0.005). NUDT1 mRNA levels were omitted due to low and unreliable expression levels. The results suggest that OGG1 mRNA levels should be regarded as a, biomarker of exposure to oxidative stress with induction of DNA rather than a marker of inborn DNA repair capacity. (c) 2007 Elsevier B.V. All rights reserved.