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台湾地区尿中15-F2t-异前列腺素、黄曲霉毒素B1暴露、乙型肝炎病毒感染与肝细胞癌

Urinary 15-F2t-isoprostane, aflatoxin B1 exposure and hepatitis B virus infection and hepatocellular carcinoma in Taiwan.

作者信息

Wu Hui-Chen, Wang Qiao, Yang Hwai-I, Ahsan Habibul, Tsai Wei-Yann, Wang Li-Yu, Chen Shu-Yuan, Chen Chien-Jen, Santella Regina M

机构信息

Department of Environmental Health Sciences, Mailman School of Public Health of Columbia University, New York, NY 10032, USA.

出版信息

Carcinogenesis. 2008 May;29(5):971-6. doi: 10.1093/carcin/bgn057. Epub 2008 Feb 28.

Abstract

To evaluate the role of oxidative stress and aflatoxin exposure on risk of hepatocellular carcinoma (HCC), a case-control study nested within a large community-based cohort was conducted in Taiwan. Baseline urine samples, collected from a total of 74 incident HCC cases and 290 matched controls, were used to determine by enzyme-linked immunosorbent assays the level of urinary 15-F(2t)-isoprostane (15-F(2t)-IsoP), a biomarker of lipid peroxidation. These samples had been previously analyzed for urinary aflatoxin B(1) (AFB(1)) metabolites and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG). Pearson partial correlation coefficient analysis showed that urinary AFB(1) metabolites and 8-oxodG were significantly associated with the level of urinary 15-F(2t)-IsoP. After adjustment for potential confounding factors in a conditional logistic regression model, urinary 15-F(2t)-IsoP was significantly associated with risk of HCC [above versus below the mean odds ratio (OR) = 2.53, 95% confidence interval (CI) = 1.30-4.93]. Moreover, when compared with subjects in the lowest tertile of 15-F(2t)-IsoP, there was a trend of increasing risk of HCC (P(trend) = 0.0008), with adjusted ORs (95% CIs) of 3.87 (1.32-11.38) and 6.27 (2.17-18.13) for the second and third tertile, respectively. In addition, the combination of urinary 15-F(2t)-IsoP above the mean and chronic hepatitis B virus (HBV) infection resulted in an OR of 19.01 (95% CI = 6.67-54.17) compared with those with low urinary 15-F(2t)-IsoP and without HBV infection. These results suggest that elevated levels of urinary 15-F(2t)-IsoP may be related to increasing level of aflatoxin exposure and are associated with an increased risk of HCC.

摘要

为评估氧化应激和黄曲霉毒素暴露对肝细胞癌(HCC)风险的作用,在台湾开展了一项嵌套于大型社区队列中的病例对照研究。从总共74例新发HCC病例和290例匹配对照中收集基线尿液样本,采用酶联免疫吸附测定法测定尿中15-F(2t)-异前列腺素(15-F(2t)-IsoP)水平,其为脂质过氧化的生物标志物。这些样本此前已分析过尿中黄曲霉毒素B(1)(AFB(1))代谢物和8-氧代-7,8-二氢-2'-脱氧鸟苷(8-氧代dG)。Pearson偏相关系数分析显示,尿中AFB(1)代谢物和8-氧代dG与尿中15-F(2t)-IsoP水平显著相关。在条件逻辑回归模型中对潜在混杂因素进行校正后,尿中15-F(2t)-IsoP与HCC风险显著相关[高于均值与低于均值相比,优势比(OR)=2.53,95%置信区间(CI)=1.30 - 4.93]。此外,与15-F(2t)-IsoP处于最低三分位数的受试者相比,HCC风险有增加趋势(P趋势=0.0008),第二和第三三分位数的校正OR(95%CI)分别为3.87(1.32 - 11.38)和6.27(2.17 - 18.13)。另外,尿中15-F(2t)-IsoP高于均值且合并慢性乙型肝炎病毒(HBV)感染的情况与尿中15-F(2t)-IsoP低且无HBV感染的情况相比,OR为19.01(95%CI = 6.67 - 54.17)。这些结果表明,尿中1�-F(2t)-IsoP水平升高可能与黄曲霉毒素暴露水平增加有关,并与HCC风险增加相关。

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