title: Does aflatoxin B1 play a role in the etiology of hepatocellular carcinoma in the United States?
abstract: Previous research showed that risk factors associated with hepatocellular carcinoma (HCC) include infection with hepatitis B (HBV) and hepatitis C (HCV) viruses, exposure to aflatoxin B1 (AFB1), and liver cirrhosis, due primarily to alcohol consumption. To determine whether AFB1 may play a role in HCC in the United States, a search for AFB1 adducts and p53 alterations, potentially induced by AFB1, was conducted in the United States in 23 HCC patients with available tissue samples. The presence of AFB1 tumor-DNA and -serum lysine adducts and mutant p53 product was determined by immunoassays and codon 249 p53 mutation by restriction enzyme analysis. HBV and HCV serology and serum HBV-DNA were also determined. Thirteen patients were positive for HBV by HBs antigen or anti-HBc antigen or by polymerase chain reaction for HBV-DNA sequences. Nine patients were free of HBV and HCV markers; 5 of 22 sera tested were anti-HCV positive. p53 Protein expression, determined by immunohistochemical staining, was present in 5 of the 23 tumor tissues, whereas p53 codon 249 mutations were not observed in the 5 cases in which tissue was available for study. AFB1 tumor-DNA adducts were present in 3 of 19 tumor tissues, and in 1 of these 3 samples p53 protein was also detected. Sera from only 5 of the patients were tested for AFB1-lysine adducts, and all were positive. In these five patients, neither p53 protein nor a mutation on codon 249 was detected. The demonstration that AFB1-DNA and -lysine adducts are present in HCC patients in the United States is intriguing but requires further substantiation because of the small number of subjects in this pilot study. To elucidate the pathogenetic significance of these findings, further investigation, including studies in larger patient cohorts and properly selected controls, is warranted.
authors.affiliation: University of Texas M. D. Anderson Cancer Center, Houston, USA.
authors.forename: A
authors.initials: A
authors.lastname: Hoque
authors.forename: Y Z
authors.initials: YZ
authors.lastname: Patt
authors.forename: B
authors.initials: B
authors.lastname: Yoffe
authors.forename: J D
authors.initials: JD
authors.lastname: Groopman
authors.forename: M S
authors.initials: MS
authors.lastname: Greenblatt
authors.forename: Y J
authors.initials: YJ
authors.lastname: Zhang
authors.forename: R M
authors.initials: RM
authors.lastname: Santella
mesh_terms: D000328:Adult; D016604:Aflatoxin B1 / Q000009:adverse effects*; D000368:Aged; D002273:Carcinogens / Q000009:adverse effects*; D006528:Carcinoma, Hepatocellular / Q000209:etiology*; D017931:DNA Primers; D005260:Female; D016174:Hepacivirus / Q000276:immunology; D006515:Hepatitis B virus / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000235:genetics; D014481:United States
chemical_list: D002273:Carcinogens; D017931:DNA Primers; D016159:Tumor Suppressor Protein p53; D016604:Aflatoxin B1