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8-氧鸟嘌呤 DNA 糖基化酶 1 基因 Cys326 等位基因是吸烟和饮酒相关喉癌的危险因素。

The Cys326 allele of the 8-oxoguanine DNA N-glycosylase 1 gene as a risk factor in smoking- and drinking-associated larynx cancer.

机构信息

Department of Pediatric Dentistry, Medical University of Lodz, Lodz, Poland.

出版信息

Tohoku J Exp Med. 2009 Dec;219(4):269-75. doi: 10.1620/tjem.219.269.

Abstract

Tobacco smoke-related products and ethanol would induce oxidative modifications to the DNA bases, thereby contributing to larynx cancer. Human 8-oxoguanine DNA N-glycosylase 1 (hOGG1) deals with oxidative DNA damage, and the base changes in the hOGG1 gene may alter the susceptibility of the human cells to tobacco smoke-related compounds and/or ethanol. In the present work, we investigated the association between smoking, drinking or the Ser326Cys polymorphism of the hOGG1 gene and the risk of larynx cancer in a Polish population. It has been reported that the Ser326 allele exhibits higher activity than the Cys326 variant. In this study, 253 age-matched controls and 253 patients with larynx cancer were enrolled. The polymorphism was determined with DNA from blood lymphocytes by polymerase chain reaction. The frequencies (%) of the genotypes were Ser/Ser 65.6, Ser/Cys 30.4, and Cys/Cys 4.0 in the controls and those in patients were 55.7, 36.0 and 8.3, respectively. Stratification of individuals according to their smoking and drinking habits indicated that these habits might be significant risk factors in larynx cancer. The Ser/Cys and Cys/Cys genotypes are significantly associated with the increased risk of larynx cancer. These genotypes increased the risk ratio of larynx cancer among heavy smokers, but did not change the risk in former smokers and moderate smokers. These genotypes also increased the risk of larynx cancer in moderate and heavy drinkers. Therefore, the Cys326 allele of the hOGG1 gene may increase the risk of larynx cancer associated with smoking or alcohol consumption.

摘要

烟草烟雾相关产品和乙醇会引起 DNA 碱基的氧化修饰,从而导致喉癌。人 8-氧鸟嘌呤 DNA N-糖苷酶 1(hOGG1)处理氧化 DNA 损伤,hOGG1 基因的碱基变化可能改变人细胞对烟草烟雾相关化合物和/或乙醇的易感性。在本工作中,我们研究了吸烟、饮酒或 hOGG1 基因 Ser326Cys 多态性与波兰人群喉癌风险之间的关系。据报道,Ser326 等位基因比 Cys326 变体具有更高的活性。在这项研究中,纳入了 253 名年龄匹配的对照者和 253 名喉癌患者。通过聚合酶链反应从血液淋巴细胞中的 DNA 确定多态性。在对照组中,基因型的频率(%)为 Ser/Ser 65.6、Ser/Cys 30.4 和 Cys/Cys 4.0,而在患者中则分别为 55.7、36.0 和 8.3。根据吸烟和饮酒习惯对个体进行分层表明,这些习惯可能是喉癌的重要危险因素。Ser/Cys 和 Cys/Cys 基因型与喉癌的风险增加显著相关。这些基因型增加了重度吸烟者中喉癌的风险比,但没有改变前吸烟者和中度吸烟者的风险。这些基因型也增加了中度和重度饮酒者患喉癌的风险。因此,hOGG1 基因的 Cys326 等位基因可能会增加与吸烟或饮酒相关的喉癌风险。

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