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病例报告证据表明肝细胞癌与赭曲霉毒素中毒之间存在关系。

Case report evidence of relationships between hepatocellular carcinoma and ochratoxicosis.

机构信息

Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.

出版信息

PLoS One. 2013 Aug 20;8(8):e71423. doi: 10.1371/journal.pone.0071423. eCollection 2013.

Abstract

PURPOSE

The incidence of Hepatocellular carcinoma (HCC) is on the rise, but what is causing that trend has remained a mystery. Mycotoxins are almost entirely ignored health problems, and sometimes actually naively belittled in advanced medical care. Ochratoxin A (OTA) is one of the most abundant food contaminating mycotoxins worldwide that is carcinogenic, but no studies have evaluated its levels in HCC patients. Therefore, this study was designed to monitor the presence of OTA in the serum of HCC patients and to quantify the strength of the association between OTA and HCC.

METHODS

We conducted a case control-based study on 61 participants. Thirty-nine were HCC cases identified between 2010 and 2012 and individually matched by age, sex, residence and date of recruitment to 22 healthy controls. Serum OTA and alpha-fetoprotein levels were measured by using high-performance liquid chromatography (HPLC) and enzyme-linked immunosorbent assay, respectively.

RESULTS

HPLC analysis of 61 serum samples indicated that the highest incidence of elevated OTA was found in the HCC group and was 5-fold higher than in the control group. The concentration of OTA in the HCC group ranged between 0.129 and 10.93 ng/mL with a mean value±SD of 1.1±0.3 ng/mL, while in the normal group it ranged between 0.005 and 0.50 ng/mL with a mean value±SD of 0.201±0.02 ng/mL. The odds ratio for HCC patients presenting OTA levels above the cut-off of 0.207 (calculated by the receiver operating characteristic curve) was 9.78 (95% confidence interval = 2.9095-32.9816, P = 0.0002) with respect to normal controls, suggesting that HCC is 9.8 times as frequent in the exposed group to OTA.

CONCLUSION

Our results reveal a strong association between the presence of OTA and HCC, which may offer a coherent explanation for much of the descriptive epidemiology of HCC and suggest new avenues for analytical research.

摘要

目的

肝细胞癌(HCC)的发病率正在上升,但导致这种趋势的原因仍然是个谜。霉菌毒素是几乎完全被忽视的健康问题,有时在高级医疗保健中实际上被天真地轻视。赭曲霉毒素 A(OTA)是世界范围内最丰富的食品污染霉菌毒素之一,具有致癌性,但尚无研究评估其在 HCC 患者中的水平。因此,本研究旨在监测 HCC 患者血清中 OTA 的存在,并定量评估 OTA 与 HCC 之间的关联强度。

方法

我们对 61 名参与者进行了病例对照研究。39 例为 2010 年至 2012 年间确诊的 HCC 病例,并按年龄、性别、居住地和招募日期与 22 名健康对照个体匹配。采用高效液相色谱法(HPLC)和酶联免疫吸附试验(ELISA)分别测定血清 OTA 和甲胎蛋白水平。

结果

对 61 份血清样本的 HPLC 分析表明,OTA 升高的最高发生率出现在 HCC 组,是对照组的 5 倍。HCC 组 OTA 浓度范围为 0.129 至 10.93ng/mL,平均值±标准差为 1.1±0.3ng/mL,而正常组浓度范围为 0.005 至 0.50ng/mL,平均值±标准差为 0.201±0.02ng/mL。通过受试者工作特征曲线(ROC)计算出的 OTA 水平高于 0.207 截值的 HCC 患者的比值比(OR)为 9.78(95%置信区间为 2.9095-32.9816,P=0.0002),与正常对照组相比,暴露于 OTA 的 HCC 患者发生 HCC 的频率是对照组的 9.8 倍。

结论

我们的结果揭示了 OTA 与 HCC 之间存在强烈关联,这可能为 HCC 的描述性流行病学提供了一个一致的解释,并为分析性研究提供了新的途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/752b/3748048/8888fe852e96/pone.0071423.g001.jpg

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