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SOD 和 GPX 基因家族的遗传变异与癌症风险。

Inherited variations in the SOD and GPX gene families and cancer risk.

机构信息

Department of Genetics, Kemerovo State University, Kemerovo, Russian Federation.

出版信息

Free Radic Res. 2012 May;46(5):581-99. doi: 10.3109/10715762.2012.658515. Epub 2012 Feb 8.

Abstract

Antioxidant defence enzymes are essential protectors of living organisms against oxidative stress. These enzymes are involved in the detoxification and decomposition of harmful chemical compounds called reactive oxygen species (ROS), which are, first and foremost, a source of intracellular oxidative stress. ROS directly promote the oxidative damage of genes resulting in aberrant regulation of many vital cell processes. As a consequence, the presence of ROS can lead to genomic instability, deregulation of transcription, induction of mitogenic signal transduction pathways and replication errors, all of which may increase the risk of cancer development. Single nucleotide polymorphisms of antioxidant defence genes may significantly modify the functional activity of the encoded proteins; therefore, certain alleles can be established as risk factors for particular cancer types. In the future, these risk alleles may be utilized as genomic markers of cancer predisposition to allow for early prevention measures among carriers of these alleles. The review is devoted to common single nucleotide polymorphisms of the superoxide dismutase (SOD) and glutathione peroxidase (GPX) gene families and their impact on carcinogenesis. The predictive significance of several polymorphisms was determined, and these polymorphisms were recommended for further in-depth research.

摘要

抗氧化防御酶是生物对抗氧化应激的重要保护者。这些酶参与解毒和分解有害的化学化合物,称为活性氧物种(ROS),ROS 首先是细胞内氧化应激的来源。ROS 直接促进基因的氧化损伤,导致许多重要细胞过程的异常调节。因此,ROS 的存在可导致基因组不稳定性、转录失调、有丝分裂信号转导途径的诱导和复制错误,所有这些都可能增加癌症发展的风险。抗氧化防御基因的单核苷酸多态性可能显著改变编码蛋白的功能活性;因此,某些等位基因可以被确定为特定癌症类型的风险因素。将来,这些风险等位基因可以用作癌症易感性的基因组标记,以允许这些等位基因携带者采取早期预防措施。本文综述了超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GPX)基因家族的常见单核苷酸多态性及其对致癌作用的影响。确定了几种多态性的预测意义,并建议对这些多态性进行进一步深入研究。

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