Dominant role of hepatitis B virus and cofactor role of aflatoxin in hepatocarcinogenesis in Qidong, China

Hepatology. 2002 Nov;36(5):1214-20. doi: 10.1053/jhep.2002.36366.


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 B1 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aflatoxins / adverse effects*
  • Age Distribution
  • Aged
  • Amino Acid Sequence
  • Carcinoma, Hepatocellular / epidemiology*
  • Carcinoma, Hepatocellular / virology
  • China / epidemiology
  • Cohort Studies
  • Environmental Exposure
  • Female
  • Genetic Markers
  • Hepatitis B virus / genetics*
  • Hepatitis B, Chronic / epidemiology*
  • Humans
  • Incidence
  • Liver Neoplasms / epidemiology*
  • Liver Neoplasms / virology
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Mutation / drug effects
  • Prevalence
  • Risk Factors
  • Trans-Activators / genetics
  • Viral Regulatory and Accessory Proteins


  • Aflatoxins
  • Genetic Markers
  • Trans-Activators
  • Viral Regulatory and Accessory Proteins
  • hepatitis B virus X protein