尿液中黄曲霉毒素──DNA加合物与肝癌关系的前瞻性研究

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应用单克隆抗体系和层析柱结合高效液相色谱法测定了50例肝瘤及267名对照尿液中AFB1及其代谢物,AFP1、AFM1及AF-N7-乌嘌呤加合物,同时用RIA试剂检测其血清中HBsAg.肝癌病例尿液中含一种或一种以上AF标志物的检测率显著高于对照,RR=4.0.肝癌病例尿液中AF-N7-乌嘌呤加成物的检出率也显著高于对照,RR=7.6.尿液中如只检出AFM1、AFP1或AFB1,不同时伴有AF-N7-乌嘌呤加合物。其发生肝癌的相对危险度比同时伴有AF-N7-乌嘌呤加合物者低得多。而且在调整HBsAg及吸烟等混杂因素后,尿液中AFP1或AFB1阳性与肝癌的关系无统计学上显著性联系。过表明尿液中AF标志物,尤其是AF-N7-乌嘌呤加合物与肝癌的发生有较强联系并在个体水平上提供了AF暴露与HBV感染对肝癌发生有明显协同作用的证据。在上海,花生及酱油是饮食中AFB1的最主要来源,队列对象摄入AFB1总量的80%以上均来自这二种食品。 AFB1 and its metabolites, AFP1, AFM1, and AF-N7-oxotidine adducts were measured in 50 cases of hepatoma and 267 control urine using a monoclonal antibody system and column coupled with high performance liquid chromatography. The RIA reagent detects the serum HBsAg. The detection rate of one or more AF markers in urine of liver cancer cases was significantly higher than that of the control, RR=4.0. The detection rate of AF-N7-oxine adducts in urine of liver cancer patients was also significantly higher than that of controls, RR=7.6. If only AFM1, AFP1 or AFB1 were detected in urine, AF-N7- guanine adducts were also accompanied at the same time. The relative risk of liver cancer was much lower than that of patients with AF-N7-oxpurine adduct. Moreover, after adjusting for confounding factors such as HBsAg and smoking, there was no statistically significant relationship between the positive urinary AFP1 or AFB1 and liver cancer. It has been shown that urine AF markers, especially AF-N7-oxotidine adducts, are strongly associated with the occurrence of hepatocellular carcinoma and provide evidence of significant synergistic effects of AF exposure and HBV infection on liver cancer at the individual level. In Shanghai, peanuts and soy sauce are the main sources of AFB1 in the diet, and more than 80% of the total AFB1 intake of cohort subjects comes from these two foods.
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