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

[Guest guest]

http://onlinelibrary.wiley.com/doi/10.1111/j.1478-3231.2011.02572.x/abstract

Hepatic aflatoxin B1-DNA adducts and TP53 mutations in patients with

hepatocellular carcinoma despite low exposure to aflatoxin B1 in southern Japan

Ken Shirabe1, Takeo Toshima1, Akinobu Taketomi1, Kennichi Taguchi2, Tomoharu

Yoshizumi1, Hideaki Uchiyama1, Norifumi Harimoto3, Kiyoshi Kajiyama3, Akinori

Egashira1, Yoshihiko Maehara1

Article first published online: 28 JUN 2011

DOI: 10.1111/j.1478-3231.2011.02572.x

© 2011 Wiley & Sons A/S

Issue

Liver International

Volume 31, Issue 9, pages 1366–1372, October 2011

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.

[Guest guest]

http://onlinelibrary.wiley.com/doi/10.1111/j.1478-3231.2011.02572.x/abstract

Hepatic aflatoxin B1-DNA adducts and TP53 mutations in patients with

hepatocellular carcinoma despite low exposure to aflatoxin B1 in southern Japan

Ken Shirabe1, Takeo Toshima1, Akinobu Taketomi1, Kennichi Taguchi2, Tomoharu

Yoshizumi1, Hideaki Uchiyama1, Norifumi Harimoto3, Kiyoshi Kajiyama3, Akinori

Egashira1, Yoshihiko Maehara1

Article first published online: 28 JUN 2011

DOI: 10.1111/j.1478-3231.2011.02572.x

© 2011 Wiley & Sons A/S

Issue

Liver International

Volume 31, Issue 9, pages 1366–1372, October 2011

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.