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Association of Nad(P)H: Quinone Oxidoreductase 1 (NQO1) C609t Polymorphism and Hepatocellular Carcinoma in Taiwan Population

NAD (P)H: QUINONE OXIDOREDUCTASE 1 (NQO1)C609T基因之多形性與臺灣肝癌之相關性

摘要


研究動機:NAD(P)H: QUINONE OXIDOREDUCTASE 1 (NQO1)爲一可催化環境致癌物去毒化之抗氧化酶。此酶亦對p53功能之調控扮演一重要角色。位於核苷酸609之單一鹼基置換(C→T)之多形性降低此酶之穩定性以及功能。此研究之目的爲探討NAD(P)H: QUINONE OXIDOREDUCTASE 1 (NQO1) C609T基因之多形性與臺灣肝癌之相關性。 材料方法:吾人對116肝癌患者以及121無相關、非癌症之對照臺灣人進行以醫院爲基礎之病例-對照組研究,利用PCR-RFLP基因分折法,以探討NAD(P)H: QUINONE OXIDOREDUCTASE 1 (NQO1) C609T基因之多形性與臺灣肝癌之相關性。 結果:研究結果顯示肝癌患者與對照組基因形之頻率有顯著之差異。與C/C及C/T基因形相比,NQO1 T/T基因形顯著增加臺灣人肝癌之發生率(OR=2.01; 95% CI=1.06-3.72)。 結論:NQO1基因之多形性可能在臺灣人肝癌之致癌性扮演一重要角色。須作進一步研究以探討NQO1改變癌症之危險性之機制。

關鍵字

NQO1 C609T 基因多形性 肝癌

並列摘要


Introduction: NAD(P)H: quinone oxidoreductase 1 (NQO1) is an antioxidant enzyme that catalyzes the detoxification of environmental carcinogens and plays an important role in regulating p53 functions. A single base substitution (C→T) polymorphism at nucleotide 609 (null-allele) of NQO1 gene impairs stability and function of this enzyme. The purpose of this study was to investigate the association of this NQO1 C609 gene polymorphism with HCC susceptibility. Materials and Methods: We conducted a hospital-based case-control study of 116 hepatocellular carcinoma (HCC) patients and 121 unrelated noncancer controls Taiwanese to investigate the association of this NQO1 C609 gene polymorphism with HCC susceptibility by using PCR-RFLP genotyping assay techniques. We examined the relationship between HCC and NQO1 genotypes after adjusting for gender, age, alcoholic drinking, and smoking status. Results: Results revealed significant differences in genotypic frequencies between HCC and control groups. NQO1 T/T genotype significantly increased the risk for developing HCC in Taiwanese population (OR=2.01; 95% CI=1.06-3.72), compared with the combined C/C and C/T genotypes. Conclusion: The findings supported the hypothesis that the NQO1 genetic polymorphism could play an important role in carcinogenesis and modulates HCC risk in Taiwanese population. The prevalence of the NQO1 T/T genotypes in this study, other studies in ethnic Chinese and Japanese populations are higher than those in Caucasian. Further studies are needed to investigate mechanisms by which the NQO1 polymorphism potentially modifies cancer risk.

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