Mechanisms of alcohol-induced hepatocellular carcinoma.
Chronic alcohol abuse is a major risk factor for hepatocellular carcinoma (HCC), the third leading cause of cancer deaths worldwide. Alcohol can also function synergistically with other risk factors to cause HCC. Hence, alcohol consumption is a major factor affecting hepatic carcinogenesis in millions and the cause of a substantial public health burden. Chronic alcohol consumption interferes with several host anti-tumor mechanisms, thereby facilitating hepatocyte proliferation and tumorigenesis. This review summarizes the major mechanisms of alcohol-induced HCC. These include pathways of ethanol metabolism, alcohol-induced oxidative stress and hypomethylation of DNA, and interplay of alcohol with iron elevation, retinoid metabolism, the immune system, inflammatory pathways, and neoangiogenesis. The relevance of each pathway in affecting HCC transformation is a topic of intense investigation. Ongoing research will enhance our insight into the alcohol-induced occurrence of HCC and offer hope in developing better therapeutics.
Critical Care Medicine Department, Department of Health and Human Services, Clinical Center, National Institutes of Health, Bethesda, MD, USA.
Sreetha
S
Sidharthan
Laboratory of Immunoregulation, Department of Health and Human Services, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bldg10, Rm.11N204, Bethesda, MD 20892, USA.
Shyam
S
Kottilil
Alcohol; Carcinogenesis; HCC