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与泌尿生殖系统肿瘤相关的N-乙酰转移酶和谷胱甘肽S-转移酶的基因多态性。综述。

Genetic polymorphism of N-acetyltransferase and glutathione S-transferase related to neoplasm of genitourinary system. Minireview.

作者信息

Reszka E, Wasowicz W

机构信息

Department of Toxicology and Carcinogenesis, Nofer Institute of Occupational Medicine, 90-950 Lodz, Poland.

出版信息

Neoplasma. 2002;49(4):209-16.

Abstract

Genetically determined risk factors may considerably contribute to the development of neoplastic diseases, including neoplasm of urinary organs, e.g. bladder and prostate cancers. It is believed that they may result, among others, from the differences in the metabolism of environmental carcinogens and mechanisms of DNA repair. There is a clear evidence that the kind and rate of metabolism is genetically determined by polymorphic enzyme coding genes participating in the process of xenobiotic transformation. Genetic polymorphism has been confirmed for a number of enzymes involved in the reaction of oxidation or conjugation of exo- and endogenous xenobioties. Gene variability may alter the expression or enzymatic activity of coded enzymes. Therefore, the cancer risk assessment should also be based on individual differences in the ability to activate (phase I) or to detoxify (phase II) possible carcinogens. In the present study, the information on the significance of glutathione 5-transferase (GST) and N-acetyltransferase (NAT) gene families in protection of human health and incidence of various diseases is summarized. The role of hereditary polymorphisms of GST and NAT genes involved in the etiology of neoplasm of urinary organs is controversial. That is why, special attention has to be focused on the recent information on a possible role of GST and NAT polymorphisms in the predisposition to urinary bladder, prostate and urothelial transitional cell carcinoma.

摘要

遗传决定的风险因素可能在很大程度上促使肿瘤性疾病的发生,包括泌尿器官肿瘤,如膀胱癌和前列腺癌。人们认为,这些因素可能尤其源于环境致癌物代谢及DNA修复机制的差异。有明确证据表明,代谢的类型和速率由参与外源性物质转化过程的多态性酶编码基因在遗传上决定。对于许多参与外源性和内源性异生物质氧化或结合反应的酶,已证实存在基因多态性。基因变异性可能会改变编码酶的表达或酶活性。因此,癌症风险评估也应基于激活(I期)或解毒(II期)潜在致癌物能力的个体差异。在本研究中,总结了谷胱甘肽S-转移酶(GST)和N-乙酰转移酶(NAT)基因家族在保护人类健康及各种疾病发病率方面的重要性信息。GST和NAT基因的遗传多态性在泌尿器官肿瘤病因学中的作用存在争议。正因为如此,必须特别关注关于GST和NAT多态性在膀胱癌、前列腺癌和尿路上皮移行细胞癌易感性中可能作用的最新信息。

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