Yu M W, Lien J P, Chiu Y H, Santella R M, Liaw Y F, Chen C J
School of Public Health, College of Public Health, National Taiwan University, Taipei, Taiwan.
J Hepatol. 1997 Aug;27(2):320-30. doi: 10.1016/s0168-8278(97)80178-x.
BACKGROUND/AIMS: Aflatoxins (AFs) are established hepatic carcinogens in several animal species. This study was performed to establish whether aflatoxin exposure may affect the risk of developing hepatocellular carcinoma in chronic hepatitis B virus carriers.
Urinary AF metabolites were measured for 43 HCC cases and 86 matched controls nested in a cohort of 7342 men in Taiwan. Thirty hepatocellular carcinoma cases and 63 controls were also tested for AFB1-albumin adducts.
There was a dose-response relationship between urinary AFM1 levels and risk of hepatocellular carcinoma in chronic hepatitis B virus carriers. Comparing the highest with the lowest tertile of urinary AFM1 levels, the multivariate-adjusted odds ratio (OR) was 6.0 (95% confidence interval (CI) = 1.2-29.0). The hepatocellular carcinoma risk associated with AFB1 exposure was more striking among the hepatitis B virus carriers with detectable AFB1-N7-guanine adducts in urine. Compared with chronic hepatitis B virus carriers who were negative for AFB1-albumin adducts and urinary AFB1-N7-guanine, no elevated risk was observed for those who were positive for either marker. But an extremely high risk of hepatocellular carcinoma among those having both markers was found (OR = 10.0, 95% CI = 1.6-60.9). The proportion of AFB1 converted to AFM1 decreased with the progress of liver disease, whereas the formation of AFP1 increased. The difference in patterns of AFB1 metabolite formation was an independent risk factor for hepatocellular carcinoma after adjustment for total AFB1 excretion. There was a synergistic interaction between glutathione S-transferase M1 genotype and AFB1 exposure in hepatocellular carcinoma risk.
AFB1 intake and expression of enzymes involved in AFB1 activation/detoxification may play an important role in hepatitis B virus-related hepatocarcinogenesis.
背景/目的：黄曲霉毒素（AFs）在多种动物物种中已被确认为肝脏致癌物。本研究旨在确定黄曲霉毒素暴露是否会影响慢性乙型肝炎病毒携带者发生肝细胞癌的风险。
在台湾的7342名男性队列中，对43例肝细胞癌病例和86例匹配对照进行尿AF代谢物检测。还对30例肝细胞癌病例和63例对照进行了AFB1-白蛋白加合物检测。
慢性乙型肝炎病毒携带者尿AFM1水平与肝细胞癌风险之间存在剂量反应关系。将尿AFM1水平最高三分位数与最低三分位数进行比较，多变量调整后的优势比（OR）为6.0（95%置信区间（CI）=1.2 - 29.0）。在尿液中可检测到AFB1-N7-鸟嘌呤加合物的乙型肝炎病毒携带者中，与AFB1暴露相关的肝细胞癌风险更为显著。与AFB1-白蛋白加合物和尿AFB1-N7-鸟嘌呤均为阴性的慢性乙型肝炎病毒携带者相比，单一标志物阳性者未观察到风险升高。但发现两种标志物均阳性者患肝细胞癌的风险极高（OR = 10.0，95%CI = 1.6 - 60.9）。随着肝病进展，AFB1转化为AFM1的比例降低，而AFP1的形成增加。在调整总AFB1排泄量后，AFB1代谢物形成模式的差异是肝细胞癌独立的危险因素。谷胱甘肽S-转移酶M1基因型与AFB1暴露在肝细胞癌风险方面存在协同相互作用。
AFB1摄入以及参与AFB1激活/解毒的酶的表达可能在乙型肝炎病毒相关的肝癌发生中起重要作用。
