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氧化应激相关酶基因的上位性对口腔癌风险的调节作用。

Epistasis of oxidative stress-related enzyme genes on modulating the risks in oral cavity cancer.

机构信息

Division of Plastic Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan.

出版信息

Clin Chim Acta. 2010 Nov 11;411(21-22):1705-10. doi: 10.1016/j.cca.2010.07.007. Epub 2010 Jul 17.

Abstract

BACKGROUND

The aim of this study was to evaluate the risks of the polymorphisms of oxidant stress-related enzymes on patients with oral cavity cancer by genotyping of manganese superoxide dismutase (MnSOD [1183T>C]), myeloperoxidase (MPO [-463G>A]), catalase (CAT [-15A>T]) and glutathione peroxidases 1 (GPx1 [Pro198Leu]).

METHODS

A case-control study was conducted on 122 biopsy-proven oral cavity cancer patients with, at least, one of the past habits of cigarette smoking, alcohol drinking or betel-quid chewing, and 122 approximately age- and habit-matched controls.

RESULTS

The independent risks of the polymorphisms for each enzyme on carcinogenicity were non-significant. The 2-order gene-gene interactions of the polymorphisms, assessed by using a logistic regression model, on risk did not show significant changes, neither. However, the epistasis, assessed by multifactor dimensionality reduction (MDR) for three-order (CAT, MnSOD, and MPO) and four-order was significant. Additionally, the fact that the levels of O(2)(-), GSSG and total GSH in the patients were significantly different according to certain genotypes which revealed that the polymorphisms of these enzymes could affect these parameters to some extent.

CONCLUSIONS

The results suggested that the genetic-effects of the polymorphisms of these enzymes could slightly modify the risk in oral cavity cancer development individually, but significantly when they functioned together.

摘要

背景

本研究旨在通过对锰超氧化物歧化酶(MnSOD [1183T>C])、髓过氧化物酶(MPO [-463G>A])、过氧化氢酶(CAT [-15A>T])和谷胱甘肽过氧化物酶 1(GPx1 [Pro198Leu])的基因分型,评估氧化应激相关酶的多态性对口腔癌患者的风险。

方法

对 122 例经活检证实的口腔癌患者(至少有吸烟、饮酒或咀嚼槟榔的过去习惯之一)和 122 例年龄和习惯匹配的对照进行病例对照研究。

结果

每种酶的多态性对致癌性的独立风险无显著性。通过逻辑回归模型评估的多态性的 2 阶基因-基因相互作用对风险也没有显著变化。然而,通过多因素降维(MDR)对三阶(CAT、MnSOD 和 MPO)和四阶的上位性进行评估是显著的。此外,根据某些基因型,患者的 O(2)(-)、GSSG 和总 GSH 水平存在显著差异,这表明这些酶的多态性在一定程度上可以影响这些参数。

结论

结果表明,这些酶的多态性的遗传效应可能单独轻微改变口腔癌发展的风险,但当它们共同作用时,风险会显著增加。

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