title: Hepatic aflatoxin B1-DNA adducts and TP53 mutations in patients with hepatocellular carcinoma despite low exposure to aflatoxin B1 in southern Japan.
abstract: OBJECTIVE
  Hepatitis B or C virus infection is considered to be the main cause of hepatocellular carcinoma (HCC) in Japan. Aflatoxin B1 (AFB1) is a carcinogen associated with HCC in regions with high exposure. Mutations in codon 249, exon 7 are a hallmark of AFB1 exposure. Therefore, to clarify the role of AFB1 in hepatocarcinogenesis, we examined AFB1-DNA in liver tissue and sequenced TP53 in Japanese patients with HCC.
  
  
  METHODS
  Hepatocyte AFB1-DNA adducts were determined immunohistochemically and direct sequencing of TP53 was done to determine mutations in 188 of 279 patients who underwent hepatic resection for HCC. We assessed hepatitis C virus antibodies (HCV Ab) and HBSAg expression; patients without either were defined as having non-B non-C hepatocellular carcinoma (NBNC HCC).
  
  
  RESULTS
  AFB1-DNA adducts were detected in hepatocyte nuclei in 18/279 patients (6%), including 13/83 patients (16%) with NBNC HCC and 5/51 patients (10%) expressing hepatitis B surface antigen. None of the patients with HCV Ab (n=136) were positive for AFB1-DNA. The incidence of the G-T transversion and mutations in exon 7 of TP53 in patients with AFB1-DNA adducts were significantly higher in patients with than in patients without AFB1-DNA adducts. All three patients with the codon 249 AGG-AGT mutation had AFB1-DNA adducts.
  
  
  CONCLUSIONS
  Although exposure to AFB1 is thought to be low in Japan, it is still associated with hepatocarcinogenesis, particularly in NBNC HCC and hepatitis B individuals.
authors: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. kshirabe@surg2.med.kyushu-u.ac.jp
authors: Ken
authors: K
authors: Shirabe
authors: Takeo
authors: T
authors: Toshima
authors: Akinobu
authors: A
authors: Taketomi
authors: Kennichi
authors: K
authors: Taguchi
authors: Tomoharu
authors: T
authors: Yoshizumi
authors: Hideaki
authors: H
authors: Uchiyama
authors: Norifumi
authors: N
authors: Harimoto
authors: Kiyoshi
authors: K
authors: Kajiyama
authors: Akinori
authors: A
authors: Egashira
authors: Yoshihiko
authors: Y
authors: Maehara
mesh_terms: D000293:Adolescent; D000328:Adult; D016604:Aflatoxin B1 / Q000009:adverse effects / Q000032:analysis*; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000737:chemistry* / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D016009:Chi-Square Distribution; D018736:DNA Adducts / Q000009:adverse effects / Q000032:analysis*; D004252:DNA Mutational Analysis; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000097:blood; D018937:Hepatitis C Antibodies / Q000097:blood; D006801:Humans; D007150:Immunohistochemistry; D007564:Japan / Q000453:epidemiology; D008113:Liver Neoplasms / Q000737:chemistry* / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018570:Risk Assessment; D012307:Risk Factors; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D055815:Young Adult
chemical_list: D018736:DNA Adducts; D006514:Hepatitis B Surface Antigens; D018937:Hepatitis C Antibodies; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C072611:aflatoxin B1-DNA adduct; D016604:Aflatoxin B1