尿液中黄曲霉毒素—DNA加合物与肝癌关系的前瞻性研究

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。

A PROSPECTIVE STUDY ON CORRLATION BETWEEN AFLATOXIN-DNA ADDUCTS IN URINE AND LIVER CANCER RISK IN SHANGHAI

To assess the relationship between aflatoxin(AF)exposure and risk of hepatocellular carcinoma(HCC), urine samples from 50 cases of HCC and 267 controls were analyzed for AFB1 and its principal metabolites, AFP1 and M1, as well as for AFB-N7-quanine adducts by monoclonal antibody affinity chromatography and HPLC. HBsAg was measured by radio immunoassay. Each of the four AF markers was more frequently present among HCC cases than controls. For 36 of 50 HCC cases and 109 of 267 controls,at least one of the four AF markers was positive(RR4. 0; 95%CL2.0,7.8). The risk for HCC was higher among people who excreted AFB-N7-quanine adducts in their urine (the RR was 7. 6:95%CL3.2, 18.0). In the absence of AFB-N7-quanine, the RR associated with the presence of AFB1. AFB1 or AFP1 ranged from 2. 6 to 3. 1,and were not statistically significant for AFP1 and AFB1 (adjusted for potential confounders which included HBsAg positivity and cigarette smoking). On the other hand, when AFB-N7-quanine was present , the RR associated with positive AFB1. AFM1 or AFP1 ranged from 6. 3 to 10. 3, and all were statistically significant (adjusted for HBsAg positivity and cigarette smoking). The result demonstrates the importance of AFB-N7-quanine in correlation with other AF markers as a predictor for HCC risk in this Cohort, and provides the epidemiological evidence of synergistic interaction at the individual level between AF exposure and HBV infection on HCC risk. In addition, the result shows that, peanut and soy sauce appear to be the most important sources of dietary AFB1 exposure in Shanghai, responsible for over 80% of the total exposure among Cohort subjects.