非小细胞肺癌患者 hOGG1基因启动子区域突变的研究 Translated title: Mutational Analysis of hOGG1 Gene Promoter in Patients with Non-small Cell Lung Cancer

Abstract

背景与目的

8-羟基鸟嘌呤DNA糖苷酶（8-hydroxygumine DNA glycosylase 1, OGG1）是一种DNA修复酶，可以从DNA切除修复8-羟基鸟嘌呤（8-dihydro-8-oxoguanine, 8-OH-G）。人类 OGG1基因（ hOGG1）的多态性可能会改变酶的活性而影响个体修复损伤DNA的能力，促进癌变。然而， hOGG1基因启动子区域的突变与非小细胞肺癌（non-small cell lung cancer, NSCLC）的关系尚不明晰。我们拟探讨 hOGG1基因启动子区域的突变与NSCLC发生发展的潜在关系。

方法

选取苏州大学附属第一医院2003年1月-2005年12月新鲜手术切除的40例NSCLC组织标本，采用PCR-SSCP和直接测序的方法检测NSCLC及其对应的癌旁组织中 hOGG1基因启动子区域的突变。

结果

在40例NSCLC患者中未发现 hOGG1基因启动子区域的异常突变，但发现单核苷酸多态位点rs159153与TNM分期明显相关（ P=0.008）；同时发现吸烟者中淋巴结转移率明显较低（ P=0.034）。

结论

单核苷酸多态位点rs159153和吸烟史可能对NSCLC的侵袭和转移潜在性提供预测。

Translated abstract

Background and objective

8-hydroxygumine DNA glycosylase 1 (OGG1) is a DNA repair enzyme, which can repair damaged DNA by excising 8-dihydro-8-oxoguanine (8-OH-G). Polymorphisms in human OGG1 gene ( hOGG1) may alter glycosylase activity, thereby affects its repair to the damaged DNA, resulting in contribution to carcinogenesis. However, an association of genetic variants of hOGG1 promoter with non-small cell lung cancer (NSCLC) remains unclear. The present study aims to explore whether there are mutations in the promoter region of hOGG1 and the association of the potential genetic variants with NSCLC.

Methods

Forty lung cancer patients were enrolled from January, 2003 to December, 2005 in the first affiliated hospital of Soochow University. PCR-SSCP followed by direct sequencing were performed to detect mutations within the promoter region of the hOGG1 gene in NSCLC and corresponding paracancerous lung tissues.

Results

No abnormal mutation was found in the promoter region of the hOGG1 gene in 40 patients with NSCLC. However, a SNP rs159153 in hOGG1 was significantly associated with higher TNM stage ( P=0.008). Moreover, lower frequency of lymph node metastasis was observed in smoker patients with NSCLC ( P=0.034).

Conclusion

The SNP rs159153 in the promoter region of the hOGG1 gene and smoking history may effectively forebode the aggressiveness and metastatic potential of NSCLC.