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食管癌中NQO1基因多态性、NQO1基因表达及PAH-DNA加合物的研究。一项来自伊朗的病例对照研究。

Investigation of NQO1 genetic polymorphism, NQO1 gene expression and PAH-DNA adducts in ESCC. A case-control study from Iran.

作者信息

Marjani H A, Biramijamal F, Rakhshani N, Hossein-Nezhad A, Malekzadeh R

机构信息

National Institute of Genetic Engineering & Biotechnology, Tehran, Iran.

出版信息

Genet Mol Res. 2010 Feb 9;9(1):239-49. doi: 10.4238/vol9-1gmr693.

DOI:10.4238/vol9-1gmr693
PMID:20198579
Abstract

We evaluated the effect of NQO1 genetic variation on PAH-DNA adducts in esophageal squamous cell carcinoma (ESCC) in northeast Iran. Golestan Province in northeast of Iran has one of the highest esophageal cancer incidences in the world. The study included 93 ESCC cases and 50 control individuals who were seen at the clinical cancer center in Golestan province. NQO1 C609T genotypes were determined by PCR-RFLP analysis. NQO1 gene expression in tissue samples was determined by quantitative real-time PCR. Immunohistochemical techniques were used to detect PAH-DNA adducts in ESCC and normal esophageal tissues. The distributions of NQO1 genetic polymorphism between cases and the control group were not significantly different. NQO1 gene expression was not higher in tumor tissues than in normal esophageal tissues adjacent to the ESCC; expression was higher in tumor tissues that had the NQO1 T allele. NQO1 gene expression was high in normal esophageal tissues. The level of PAH-DNA adducts was significantly higher in ESCC tissues of cases than in normal tissues adjacent to tumor tissues and in normal esophageal tissues of healthy controls. There were no significant differences between the adduct levels of normal esophageal tissues of patients and controls. There was also no significant relationship between cigarette smoking and PAH-DNA adducts. We concluded that PAHs are a risk factor for ESCC and that PAH-DNA adducts have potential as a biomarker for risk of ESCC.

摘要

我们评估了NQO1基因变异对伊朗东北部食管鳞状细胞癌(ESCC)中多环芳烃-DNA加合物的影响。伊朗东北部的戈勒斯坦省是世界上食管癌发病率最高的地区之一。该研究纳入了93例ESCC患者和50名对照个体,这些个体均来自戈勒斯坦省临床癌症中心。通过聚合酶链反应-限制性片段长度多态性分析(PCR-RFLP)确定NQO1 C609T基因型。采用定量实时聚合酶链反应测定组织样本中NQO1基因的表达。运用免疫组织化学技术检测ESCC组织和正常食管组织中的多环芳烃-DNA加合物。病例组与对照组之间NQO1基因多态性的分布无显著差异。ESCC肿瘤组织中NQO1基因表达并不高于相邻的正常食管组织;具有NQO1 T等位基因的肿瘤组织中表达更高。正常食管组织中NQO1基因表达较高。ESCC患者组织中多环芳烃-DNA加合物水平显著高于肿瘤组织相邻的正常组织以及健康对照者的正常食管组织。患者与对照者正常食管组织的加合物水平无显著差异。吸烟与多环芳烃-DNA加合物之间也无显著关联。我们得出结论,多环芳烃是ESCC的一个风险因素,且多环芳烃-DNA加合物有潜力作为ESCC风险的生物标志物。

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