Dominant role of hepatitis B virus and cofactor role of aflatoxin in hepatocarcinogenesis in Qidong, China
Dominant role of hepatitis B virus and cofactor role of aflatoxin in hepatocarcinogenesis in Qidong, China
复制标题
DOI：
10.1053/jhep.2002.36366
复制
发表时间：
2002-11-01
期刊：
影响因子：
13.5
通讯作者：
Sun, ZT
中科院分区：
文献类型：
--
作者：
Ming, L;Thorgeirsson, SS;Sun, ZT
我们评估了乙型肝炎病毒（HBV）、丙型肝炎病毒（HCV）和黄曲霉毒素在中国启东地区引起肝细胞癌（HCC）的单独和联合效应。对181例经病理诊断的HCC患者进行了连续的乙型肝炎表面抗原（HBsAg）、抗hbc、HBV X基因序列、抗hcv、249ser-p53突变和慢性肝炎病理检测。181例HCC病例均有HBV感染和肝炎病理标志物；119例中仅有6例合并HCV感染。在54%（97/181）的HCC病例中发现249ser-p53突变，在所有来自肝炎队列的7例组织分析病例中发现249ser-p53突变，但在来自北京的42例匹配病例中没有发现249ser-p53突变。这7例中黄曲霉毒素b1的估计累积剂量范围为0.13至0.49 mg/kg。对145名慢性乙型肝炎男性患者13.25年的随访数据显示，黄曲霉毒素暴露的相对风险为3.5（1.5-8.1）。使用249ser-p53突变作为黄曲霉毒素暴露的标记，发现了类似的相对风险。综上所述，启东市HCC病例中HBV肝炎普遍存在，而HCV对HCC的影响较小。249ser-p53突变似乎是由黄曲霉毒素和HBV感染共同暴露造成的。即使是适度的黄曲霉毒素暴露也会使感染乙肝病毒的男性患HCC的风险增加两倍。
We assessed the separate and combined effects of hepatitis B virus (HBV), hepatitis C virus (HCV), and aflatoxin in causing hepatocellular carcinoma (HCC) in Qidong, China. A consecutive series of 181 pathologic-diagnosed HCC cases were studied for hepatitis B surface antigen (HBsAg), anti-HBc, HBV X gene sequence, anti-HCV, the 249ser-p53 mutation, and chronic hepatitis pathology. Each of the 181 incident HCC cases had markers for HBV infection and hepatitis pathology; only 6 of 119 cases were coinfected with HCV. The 249ser-p53 mutation was found in 54% (97/181) of HCC cases and in all 7 cases with tissue for analysis from the hepatitis cohort but in none of 42 matched cases from Beijing. The estimated cumulative dose of aflatoxin B I in these 7 cases ranged from 0.13 to 0.49 mg/kg. Follow-up data through 13.25 years on a cohort of 145 men with chronic HBV hepatitis showed that the relative risk from aflatoxin exposure was 3.5 (1.5-8.1). A similar relative risk was found using 249ser-p53 mutation as a marker for aflatoxin exposure. In conclusion, HBV hepatitis is ubiquitous in Qidong HCC cases, whereas HCV contributes little to its risk. The 249ser-p53 mutation appears to result from coexposure to aflatoxin and HBV infection. Even modest levels of aflatoxin exposure tripled the risk of HCC in HBV-infected men.