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中国代谢酶基因表达与食管鳞状细胞癌之间的关联。

Association between gene expression of metabolizing enzymes and esophageal squamous cell carcinomas in China.

作者信息

Liu Ran, Yin Lihong, Pu Yuepu

机构信息

Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, P.R. China.

出版信息

Genet Test Mol Biomarkers. 2012 Oct;16(10):1211-7. doi: 10.1089/gtmb.2012.0032. Epub 2012 Aug 1.

Abstract

Epidemiological studies have indicated that the incidence of esophageal squamous cell carcinoma (ESCC) is associated with environmental exposure to mutagens and carcinogens. To determine whether the basal expression level of genes involved in metabolism of carcinogens is associated with the risk of ESCC, a case-control study of 100 patients with newly diagnosed, untreated ESCC and 117 healthy controls was performed, and the relative expression levels of four metabolism genes (CYP2E1, GSTP1, MTHFR, and NQO1) were determined with quantitative real-time reverse transcription-polymerase chain reaction in peripheral blood mononuclear cells (PBMCs). Analyzed with the mean of relative expression level in the controls as the cut-off point, the result exhibited that the increased risk for ESCC was significantly associated with reduced expression of GSTP1 (odds ratio [OR]=3.644, 95% confidence interval [CI: 1.947-6.823) and NQO1 (OR=1.870, 95% CI: 1.046-3.345). When adjusted for age, sex, smoking status, and alcohol use, the increased risk for ESCC was significantly associated with reduced expression of GSTP1, MTHFR, and NQO1, and GSTP1 mRNA showed a steady association with the risk for ESCC (OR=2.640) in the model of stepwise regression analysis. Reduced expression of GSTP1 in PBMCs was significantly associated with the risk for ESCC, suggesting an important etiology clue to the early progression of ESCC in the Huaian population of China.

摘要

流行病学研究表明,食管鳞状细胞癌(ESCC)的发病率与环境中诱变剂和致癌物的暴露有关。为了确定参与致癌物代谢的基因的基础表达水平是否与ESCC风险相关,我们进行了一项病例对照研究,纳入100例新诊断的未经治疗的ESCC患者和117例健康对照,采用定量实时逆转录-聚合酶链反应测定外周血单个核细胞(PBMC)中四个代谢基因(CYP2E1、GSTP1、MTHFR和NQO1)的相对表达水平。以对照组相对表达水平的均值作为切点进行分析,结果显示,ESCC风险增加与GSTP1表达降低(比值比[OR]=3.644,95%置信区间[CI:1.947 - 6.823])和NQO1表达降低(OR=1.870,95% CI:1.046 - 3.345)显著相关。在对年龄、性别、吸烟状况和饮酒情况进行校正后,ESCC风险增加与GSTP1、MTHFR和NQO1表达降低显著相关,并且在逐步回归分析模型中,GSTP1 mRNA与ESCC风险呈现稳定的相关性(OR=2.640)。PBMC中GSTP1表达降低与ESCC风险显著相关,这为中国淮安人群ESCC的早期进展提供了重要的病因线索。

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