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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board Member: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Sies, Helmut / Turk, Boris / Wittinghofer, Alfred

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1437-4315
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Volume 387, Issue 4 (Apr 2006)

Issues

Risk factors and mechanisms of hepatocarcinogenesis with special emphasis on alcohol and oxidative stress

Helmut K. Seitz
  • Department of Medicine and Laboratory of Alcohol Research, Liver Disease and Nutrition, Salem Medical Center, D-69121 Heidelberg, Germany
/ Felix Stickel
  • Institute of Clinical Pharmacology, University of Berne, CH-3010 Berne, Switzerland
Published Online: 2006-04-11 | DOI: https://doi.org/10.1515/BC.2006.047

Abstract

Hepatocellular cancer is the fifth most frequent cancer in men and the eighth in women worldwide. Established risk factors are chronic hepatitis B and C infection, chronic heavy alcohol consumption, obesity and type 2 diabetes, tobacco use, use of oral contraceptives, and aflatoxin-contaminated food. Almost 90% of all hepatocellular carcinomas develop in cirrhotic livers. In Western countries, attributable risks are highest for cirrhosis due to chronic alcohol abuse and viral hepatitis B and C infection. Among those with alcoholic cirrhosis, the annual incidence of hepatocellular cancer is 1–2%. An important mechanism implicated in alcohol-related hepatocarcinogenesis is oxidative stress from alcohol metabolism, inflammation, and increased iron storage. Ethanol-induced cytochrome P-450 2E1 produces various reactive oxygen species, leading to the formation of lipid peroxides such as 4-hydroxy-nonenal. Furthermore, alcohol impairs the antioxidant defense system, resulting in mitochondrial damage and apoptosis. Chronic alcohol exposure elicits hepatocyte hyperregeneration due to the activation of survival factors and interference with retinoid metabolism. Direct DNA damage results from acetaldehyde, which can bind to DNA, inhibit DNA repair systems, and lead to the formation of carcinogenic exocyclic DNA etheno adducts. Finally, chronic alcohol abuse interferes with methyl group transfer and may thereby alter gene expression.

Keywords: acetaldehyde; cytochrome P4502E1; hepatitis; methyl group transfer; reactive oxygen species; retinoids

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About the article

Corresponding author


Published Online: 2006-04-11

Published in Print: 2006-04-01


Citation Information: Biological Chemistry, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/BC.2006.047. Export Citation

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