The human 8-oxoguanine DNA N-glycosylase 1 (hOGG1) DNA repair enzyme and its association with lung cancer risk
The human 8-oxoguanine DNA N-glycosylase 1 (hOGG1) DNA repair enzyme and its association with lung cancer risk
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DOI：
10.1097/00008571-200402000-00004
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发表时间：
2004-02-01
期刊：
影响因子：
--
通讯作者：
Lazarus, P
中科院分区：
文献类型：
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作者：
Park, J;Chen, L;Lazarus, P
目的人8-氧代鸟嘌呤DNA N-糖基化酶1基因编码的DNA糖基化酶参与氧化损伤DNA中8-羟基-2-脱氧鸟嘌呤的碱基切除修复，并在肺组织中表达。基于体外功能分析，hOGG 1基因中的密码子326多态性被认为降低了DNA修复酶活性。本研究的目的是确定密码子326多态性是否与个体肺癌风险的变化显着相关。方法为了确定hOGG 1是否在肺癌风险中发挥作用，我们测量了肺癌患者和匹配的非癌症对照中Ser 326 Cys多态性的患病率。通过PCR-限制性片段长度多态性分析从179例高加索人肺癌病例和358例对照中分离的基因组DNA进行hOGG 1基因分型，这些病例和对照按种族、性别和年龄（+/- 5岁）以1：2的比例单独匹配。肺癌风险与吸烟的剂量依赖性效应。结果hOGG 1 326 Ser/Cys基因多态性与肺癌发生的危险性显著相关（P < 0. 05），hOGG 1 326 Ser/Cys基因多态性与肺癌发生的危险性显著相关（P < 0. 05），hOGG 1 326 Ser/Cys基因多态性与肺癌发生的危险性显著相关（P < 0. 05（OR = 1.9，95% CI = 1.2-2.9）和hOGG 1326（cys/cys）基因型（OR = 3.8，95% CI = 1.4-10.6）。hOGG 1（326）ser/cys基因型（OR = 1.7，95%CI = 1.1-2.8）和hOGG 1 326 cys/cys基因型（OR = 4.9，95%CI = 1.5-16.1）的吸烟者患肺癌的风险增加。hOGG 1基因型与肺癌风险之间存在显着相关性，并与吸烟呈剂量依赖性效应。所有非小细胞肺癌患者hOGG 1基因型变异的风险显著增加。结论hOGG 1基因Ser 326 Cys多态性在肺癌风险中起重要作用，并与烟草烟雾暴露有关。
Objective The human 8-oxoguanine DNA N-glycosylase 1 gene encodes a DNA glycosylase that is involved in the base excision repair of 8-hydroxy-2-deoxyguanine from oxidatively-damaged DNA and expressed in lung tissue. The codon 326 polymorphism in the hOGG1 gene has been suggested to reduce DNA repair enzyme activity based on in vitro functional analysis. The goal of the present study is to determine whether the codon 326 polymorphism was significantly associated with alterations in individual risk for lung cancer.Methods To determine whether hOGG1 plays a role in risk for lung cancer, we measured the prevalence of the Ser326Cys polymorphism in incident lung cancer patients and matched non-cancer controls. hOGG1 genotyping was performed by PCR-restriction fragment length polymorphism analysis of genomic DNA isolated from 179 Caucasian lung cancer cases and 358 controls individually matched in a 1:2 ratio by race-, sex- and age (+/- 5 years). lung cancer risk with a dose-dependent effect with smoking. Significantly increased risk for variant hOGG1 genotypes was observed for all non-small cell lung cancer patients.Results Significantly increased risk for lung cancer was observed for both the hOGG1 326 Ser/Cys (odds ratio [OR] = 1.9, 95% confidence interval [CI] = 1.2-2.9) and hOGG1 326(cys/cys) genotypes (OR = 3.8,95% Cl = 1.4-10.6). The increased risk for lung cancer was observed for subjects with both the hOGG1 (326)ser/Cys (OR = 1.7, 95% Cl = 1.1-2.8) and hOGG1 326cys/cys genotypes (OR = 4.9, 95% Cl = 1.5-16.1) in ever-smokers. A significant association was found between hOGG1 genotypes and lung cancer risk with a dose-dependent effect with smoking. Significantly increased risk for variant hOGG1 genotypes was observed for all non-small cell lung cancer patients.Conclusion These results suggest that the hOGG1 Ser326Cys polymorphism plays an important role in the risk for lung cancer and is linked to exposure to tobacco smoke.