Alcohol in hepatocellular cancer.
Hepatocellular cancer accounts for almost half a million cancer deaths a year, with an escalating incidence in the Western world. Alcohol has long been recognized as a major risk factor for cancer of the liver and of other organs including oropharynx, larynx, esophagus, and possibly the breast and colon. There is compelling epidemiologic data confirming the increased risk of cancer associated with alcohol consumption, which is supported by animal experiments. Cancer of the liver associated with alcohol usually occurs in the setting of cirrhosis. Alcohol may act as a cocarcinogen, and has strong synergistic effects with other carcinogens including hepatitis B and C, aflatoxin, vinyl chloride, obesity, and diabetes mellitus. Acetaldehyde, the main metabolite of alcohol, causes hepatocellular injury, and is an important factor in causing increased oxidant stress, which damages DNA. Alcohol affects nutrition and vitamin metabolism, causing abnormalities of DNA methylation. Abnormalities of DNA methylation, a key pathway of epigenetic gene control, lead to cancer. Other nutritional and metabolic effects, for example on vitamin A metabolism, also play a key role in hepatocarcinogenesis. Alcohol enhances the effects of environmental carcinogens directly and by contributing to nutritional deficiency and impairing immunological tumor surveillance. This review summarizes the epidemiologic evidence for the role of alcohol in hepatocellular cancer, and discusses the mechanisms involved in the promotion of cancer.
Voigt
Michael D
MD
4553E JCP, 200 Hawkins Drive, Iowa City, IA 52245, USA. Michael-Voigt@Uiowa.edu
D006528:Carcinoma, Hepatocellular / Q000453:epidemiology* / Q000473:pathology*; D015897:Comorbidity; D005260:Female; D014943:Global Health; D006801:Humans; D015994:Incidence; D008108:Liver Diseases, Alcoholic / Q000453:epidemiology* / Q000473:pathology*; D008111:Liver Function Tests; D008113:Liver Neoplasms / Q000453:epidemiology* / Q000473:pathology*; D008297:Male; D011230:Precancerous Conditions / Q000473:pathology; D011379:Prognosis; D018570:Risk Assessment; D012720:Severity of Illness Index; D016019:Survival Analysis