title: Dominant role of hepatitis B virus and cofactor role of aflatoxin in hepatocarcinogenesis in Qidong, China.
abstract: 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.
authors.affiliation: National Laboratory of Molecular Oncology, Cancer Institute, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Ming
authors.forename: Snorri S
authors.initials: SS
authors.lastname: Thorgeirsson
authors.forename: Mitchell H
authors.initials: MH
authors.lastname: Gail
authors.forename: Peixin
authors.initials: P
authors.lastname: Lu
authors.forename: Curtis C
authors.initials: CC
authors.lastname: Harris
authors.forename: Nengjin
authors.initials: N
authors.lastname: Wang
authors.forename: Yongfu
authors.initials: Y
authors.lastname: Shao
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Wu
authors.forename: Guoting
authors.initials: G
authors.lastname: Liu
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Wang
authors.forename: Zongtang
authors.initials: Z
authors.lastname: Sun
mesh_terms: D000328:Adult; D000348:Aflatoxins / Q000009:adverse effects*; D017677:Age Distribution; D000368:Aged; D000595:Amino Acid Sequence; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology* / Q000821:virology; D002681:China / Q000453:epidemiology; D015331:Cohort Studies; D004781:Environmental Exposure; D005260:Female; D005819:Genetic Markers; D006515:Hepatitis B virus / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000453:epidemiology*; D006801:Humans; D015994:Incidence; D008113:Liver Neoplasms / Q000453:epidemiology* / Q000821:virology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000187:drug effects; D015995:Prevalence; D012307:Risk Factors; D015534:Trans-Activators / Q000235:genetics; D054334:Viral Regulatory and Accessory Proteins
chemical_list: D000348:Aflatoxins; D005819:Genetic Markers; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein