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Hepatic aflatoxin B1‐DNA adducts and TP53 mutations in patients with hepatocellular carcinoma despite low exposure to aflatoxin B1 in southern Japan
Author(s) -
Shirabe Ken,
Toshima Takeo,
Taketomi Akinobu,
Taguchi Kennichi,
Yoshizumi Tomoharu,
Uchiyama Hideaki,
Harimoto Norifumi,
Kajiyama Kiyoshi,
Egashira Akinori,
Maehara Yoshihiko
Publication year - 2011
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/j.1478-3231.2011.02572.x
Subject(s) - hepatocellular carcinoma , hbsag , hepatitis b virus , carcinogen , hepatitis b , medicine , aflatoxin , hepatitis c virus , gastroenterology , exon , cancer research , biology , virology , virus , gene , genetics , food science
Background & aims: 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%), including13/83 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.Conclusion: 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.