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碱基切除修复基因 hOGG1 326cys 和 XRCC1 280His 的多态性增加肝细胞癌风险。

Polymorphisms of base-excision repair genes hOGG1 326cys and XRCC1 280His increase hepatocellular carcinoma risk.

机构信息

Department of Hepatobiliary Surgery, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing 400042, China.

出版信息

Dig Dis Sci. 2012 Sep;57(9):2451-7. doi: 10.1007/s10620-012-2192-6. Epub 2012 May 8.

DOI:10.1007/s10620-012-2192-6
PMID:22565339
Abstract

BACKGROUND

DNA base-excision repair genes hOGG1 and XRCC1 play an important role in preserving genetic stability in mammalian cells against any damage caused by different factors. However, it is unclear whether altered expression and function of these DNA repair genes could lead to hepatocellular carcinoma (HCC) susceptibility.

AIMS

This study determined the association between polymorphisms of the genes encoding two key proteins of DNA base excision repair (hOGG1 ser326Cys and XRCC1 Arg 280His) and HCC risk.

METHODS

A total of 350 HCC patients (mean age of 51.1 years) and 400 healthy controls (mean age of 51.4 years) were recruited for analysis of XRCC1 and hOGG1 gene polymorphisms using PCR plus restriction fragment length polymorphism (PCR-RFLP).

RESULTS

The data showed that the hOGG1 Cys326Cys and Ser326Cys genotypes were associated with increase in HCC risk. In contrast, there was no association between HCC susceptibility and the distribution of XRCC1 His 280 His and Arg280His. However, combination of these two gene polymorphisms (XRCC1-280 Arg and hOGG1-326Cys) is associated with significant induction of HCC risk. In addition, the data also showed that XRCC1 280His polymorphism was associated with HBV infection and HCC family history to increase HCC risk. The hOGG1 326cys genotype was associated with alcohol consumption, tobacco smoke, and HBV infection to increase HCC risk.

CONCLUSION

The data from the current study demonstrated the association of these two DNA repair gene polymorphisms with HCC risk. Future studies will confirm these data before they can be used as a biomarker for assessing HCC risk.

摘要

背景

DNA 碱基切除修复基因 hOGG1 和 XRCC1 在保护哺乳动物细胞的遗传稳定性方面发挥着重要作用,使其免受各种因素造成的损伤。然而,这些 DNA 修复基因的表达和功能改变是否会导致肝细胞癌(HCC)易感性尚不清楚。

目的

本研究旨在确定编码 DNA 碱基切除修复两个关键蛋白(hOGG1 Ser326Cys 和 XRCC1 Arg280His)的基因多态性与 HCC 风险之间的关联。

方法

采用 PCR 加限制性片段长度多态性(PCR-RFLP)方法,对 350 例 HCC 患者(平均年龄 51.1 岁)和 400 例健康对照者(平均年龄 51.4 岁)的 XRCC1 和 hOGG1 基因多态性进行分析。

结果

数据显示,hOGG1 Cys326Cys 和 Ser326Cys 基因型与 HCC 风险增加相关。相比之下,XRCC1 His280His 和 Arg280His 基因型的分布与 HCC 易感性之间没有关联。然而,这两个基因多态性(XRCC1-280 Arg 和 hOGG1-326Cys)的组合与 HCC 风险的显著增加相关。此外,数据还表明,XRCC1 280His 多态性与 HBV 感染和 HCC 家族史相关,增加 HCC 风险。hOGG1 326cys 基因型与饮酒、吸烟和 HBV 感染相关,增加 HCC 风险。

结论

本研究数据表明,这两个 DNA 修复基因多态性与 HCC 风险相关。未来的研究将在这些数据得到确认后,用于评估 HCC 风险的生物标志物。

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