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

Seitz, Helmut K; Stickel, Felix (2006). Risk factors and mechanisms of hepatocarcinogenesis with special emphasis on alcohol and oxidative stress. Biological chemistry, 387(4), pp. 349-60. Berlin: Walter de Gruyter 10.1515/BC.2006.047

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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.

Item Type:

Journal Article (Further Contribution)

Division/Institute:

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Hepatology

UniBE Contributor:

Stickel, Felix

ISSN:

1431-6730

ISBN:

16606331

Publisher:

Walter de Gruyter

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:45

Last Modified:

22 Oct 2019 23:08

Publisher DOI:

10.1515/BC.2006.047

PubMed ID:

16606331

Web of Science ID:

000236955700002

BORIS DOI:

10.7892/boris.18565

URI:

https://boris.unibe.ch/id/eprint/18565 (FactScience: 757)

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