+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Susceptibility to hepatocellular carcinoma is associated with genetic variation in the enzymatic detoxification of aflatoxin B1



Susceptibility to hepatocellular carcinoma is associated with genetic variation in the enzymatic detoxification of aflatoxin B1



Proceedings of the National Academy of Sciences of the United States of America 92(6): 2384-2387



Aflatoxin B1 (AFB1) has been postulated to be a hepatocarcinogen in humans, possibly by causing p53 mutations at codon 249. AFB1 is metabolized via the phase I and II detoxification pathways; hence, genetic variation at those loci may predict susceptibility to the effects of AFB1. To test this hypothesis, genetic variation in two AFB1 detoxification genes, epoxide hydrolase (EPHX) and glutathione S-transferase M1 (GSTM1), was contrasted with the presence of serum AFB1-albumin adducts, the presence of hepatocellular carcinoma (HCC), and with p53 codon 249 mutations. Mutant alleles at both loci were significantly overrepresented in individuals with serum AFB1-albumin adducts in a cross-sectional study. Mutant alleles of EPHX were significantly overrepresented in persons with HCC, also in a case-control study. The relationship of EPHX to HCC varied by hepatitis B surface antigen status and indicated that a synergistic effect may exist. p53 codon 249 mutations were observed only among HCC patients with one or both high-risk genotypes. These results indicate that individuals with mutant genotypes at EPHX and GSTM1 may be at greater risk of developing AFB1 adducts, p53 mutations, and HCC when exposed to AFB1. Hepatitis B carriers with the high-risk genotypes may be an even greater risk than carriers with low-risk genotypes. These findings support the existence of genetic susceptibility in humans to the environmental carcinogen AFB1 and indicate that there is a synergistic increase in risk of HCC with the combination of hepatitis B virus infection and susceptible genotype.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 002706175

Download citation: RISBibTeXText

PMID: 7892276

DOI: 10.2307/2366998


Related references

Armillariella tabescen enzymatic detoxification of aflatoxin B1. Part III. Immobilized enzymatic detoxification. Annals of the new York Academy of Sciences 864: 592-599, 1998

Toll-like receptor 3 genetic variants and susceptibility to hepatocellular carcinoma and HBV-related hepatocellular carcinoma. Tumour Biology 34(3): 1589-1594, 2013

Susceptibility to aflatoxin B1-related primary hepatocellular carcinoma in mice and humans. Cancer Research 63(15): 4594-4601, 2003

Higher susceptibility to aflatoxin B(1)-related hepatocellular carcinoma in glycine N-methyltransferase knockout mice. International Journal of Cancer 128(3): 511-523, 2011

A study about the association of detoxication gene GSTM1 polymorphism and the susceptibility to aflatoxin B1-related hepatocellular carcinoma. Zhonghua Gan Zang Bing Za Zhi 13(9): 668-670, 2005

Study on the detoxication gene gstM1-gstT1-null and susceptibility to aflatoxin B1 related hepatocellular carcinoma in Guangxi. Zhonghua Liu Xing Bing Xue Za Zhi 26(10): 777-781, 2005

Armillariella tabescen enzymatic detoxification of aflatoxin B1. Laskin, A I, Li, G -X, Yu, Y -T Annals of the New York Academy of Sciences; Enzyme engineering XIV 586-591, 1998

Genetic polymorphisms in DNA repair genes XRCC4 and XRCC5 and aflatoxin B1-related hepatocellular carcinoma. Epidemiology 24(5): 671-681, 2013

Armillariella tabescen enzymatic detoxification of aflatoxin B1 (Part II). Annals of the new York Academy of Sciences 864: 586-591, 1998

Relationship between genetic polymorphism of promoter region let-7 and genetic susceptibility to hepatocellular carcinoma. Zhonghua Yu Fang Yi Xue Za Zhi 45(12): 1093-1098, 2011

Role of genetic polymorphism of glutathione-S-transferase T1 and microsomal epoxide hydrolase in aflatoxin-associated hepatocellular carcinoma. Cancer Epidemiology, Biomarkers & Prevention 10(7): 785-791, 2001

The role of epoxide hydrolase in the detoxification of the hepatocellular carcinogen, aflatoxin B1. Journal of Investigative Medicine 46(1): 149A, 1998

Field studies of aflatoxin exposure, metabolism and induction of genetic alterations in relation to HBV infection and hepatocellular carcinoma in The Gambia and Thailand. Toxicology Letters (Shannon) 64-65(SPEC ISSUE): 455-461, 1992

A case-control study on the association of hepatocellular carcinoma with genetic polymorphisms of CYP3A5 in a highly aflatoxin B1 contaminated Guangxi area. Zhonghua Gan Zang Bing Za Zhi 15(9): 705-706, 2007