Hepatic aflatoxin B1-DNA adducts and TP53 mutations in patients with hepatocellular carcinoma despite low exposure to aflatoxin B1 in southern Japan

Ken Shirabe, Takeo Toshima, Akinobu Taketomi, Kennichi Taguchi, Tomoharu Yoshizumi, Hideaki Uchiyama, Norifumi Harimoto, Kiyoshi Kajiyama, Akinori Egashira, Yoshihiko Maehara

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1366-1372
Number of pages7
JournalLiver International
Volume31
Issue number9
DOIs
Publication statusPublished - Oct 1 2011

Fingerprint

Aflatoxin B1
Hepatocellular Carcinoma
Japan
Mutation
Liver
Hepatitis C Antibodies
Codon
Hepatocytes
Exons
aflatoxin B1-DNA adduct
DNA
Virus Diseases
Hepatitis B Surface Antigens
Hepatitis B
Hepatitis B virus
Hepacivirus
Carcinogens

All Science Journal Classification (ASJC) codes

  • Hepatology

Cite this

Hepatic aflatoxin B1-DNA adducts and TP53 mutations in patients with hepatocellular carcinoma despite low exposure to aflatoxin B1 in southern Japan. / Shirabe, Ken; Toshima, Takeo; Taketomi, Akinobu; Taguchi, Kennichi; Yoshizumi, Tomoharu; Uchiyama, Hideaki; Harimoto, Norifumi; Kajiyama, Kiyoshi; Egashira, Akinori; Maehara, Yoshihiko.

In: Liver International, Vol. 31, No. 9, 01.10.2011, p. 1366-1372.

Research output: Contribution to journalArticle

Shirabe, K, Toshima, T, Taketomi, A, Taguchi, K, Yoshizumi, T, Uchiyama, H, Harimoto, N, Kajiyama, K, Egashira, A & Maehara, Y 2011, 'Hepatic aflatoxin B1-DNA adducts and TP53 mutations in patients with hepatocellular carcinoma despite low exposure to aflatoxin B1 in southern Japan', Liver International, vol. 31, no. 9, pp. 1366-1372. https://doi.org/10.1111/j.1478-3231.2011.02572.x
Shirabe, Ken ; Toshima, Takeo ; Taketomi, Akinobu ; Taguchi, Kennichi ; Yoshizumi, Tomoharu ; Uchiyama, Hideaki ; Harimoto, Norifumi ; Kajiyama, Kiyoshi ; Egashira, Akinori ; Maehara, Yoshihiko. / Hepatic aflatoxin B1-DNA adducts and TP53 mutations in patients with hepatocellular carcinoma despite low exposure to aflatoxin B1 in southern Japan. In: Liver International. 2011 ; Vol. 31, No. 9. pp. 1366-1372.
@article{85089358d75d4d44a24dc9c6c9862e28,
title = "Hepatic aflatoxin B1-DNA adducts and TP53 mutations in patients with hepatocellular carcinoma despite low exposure to aflatoxin B1 in southern Japan",
abstract = "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.",
author = "Ken Shirabe and Takeo Toshima and Akinobu Taketomi and Kennichi Taguchi and Tomoharu Yoshizumi and Hideaki Uchiyama and Norifumi Harimoto and Kiyoshi Kajiyama and Akinori Egashira and Yoshihiko Maehara",
year = "2011",
month = "10",
day = "1",
doi = "10.1111/j.1478-3231.2011.02572.x",
language = "English",
volume = "31",
pages = "1366--1372",
journal = "Liver International",
issn = "1478-3223",
publisher = "Wiley-Blackwell",
number = "9",

}

TY - JOUR

T1 - Hepatic aflatoxin B1-DNA adducts and TP53 mutations in patients with hepatocellular carcinoma despite low exposure to aflatoxin B1 in southern Japan

AU - Shirabe, Ken

AU - Toshima, Takeo

AU - Taketomi, Akinobu

AU - Taguchi, Kennichi

AU - Yoshizumi, Tomoharu

AU - Uchiyama, Hideaki

AU - Harimoto, Norifumi

AU - Kajiyama, Kiyoshi

AU - Egashira, Akinori

AU - Maehara, Yoshihiko

PY - 2011/10/1

Y1 - 2011/10/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=80052526843&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80052526843&partnerID=8YFLogxK

U2 - 10.1111/j.1478-3231.2011.02572.x

DO - 10.1111/j.1478-3231.2011.02572.x

M3 - Article

C2 - 21745313

AN - SCOPUS:80052526843

VL - 31

SP - 1366

EP - 1372

JO - Liver International

JF - Liver International

SN - 1478-3223

IS - 9

ER -