Mechanisms of alcohol-associated cancers: introduction and summary of the symposium.
Chronic alcohol consumption is associated with an increased risk for cancers of many organs, such as oral cavity, pharynx, larynx, and esophagus; breast; liver; ovary; colon; rectum; stomach; and pancreas. An understanding of the underlying mechanisms by which chronic alcohol consumption promotes carcinogenesis is important for development of appropriate strategies for prevention and treatment of alcohol-associated cancers. The National Institute on Alcohol Abuse and Alcoholism, Office of Dietary Supplements, Office of Rare Diseases, National Cancer Institute, National Institute on Drug Abuse, and National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, sponsored an international symposium on Mechanisms of Alcohol-Associated Cancers in Bethesda, Maryland, USA, October 2004. The following is a summary of the symposium. Chronic ethanol consumption may promote carcinogenesis by (1) production of acetaldehyde, which is a weak mutagen and carcinogen; (2) induction of cytochrome P450 2E1 and associated oxidative stress and conversion of procarcinogens to carcinogens; (3) depletion of S-adenosylmethionine and, consequently, induction of global DNA hypomethylation; (4) induction of increased production of inhibitory guanine nucleotide regulatory proteins and components of extracellular signal-regulated kinase-mitogen-activated protein kinase signaling; (5) accumulation of iron and associated oxidative stress; (6) inactivation of the tumor suppressor gene BRCA1 and increased estrogen responsiveness (primarily in breast); and (7) impairment of retinoic acid metabolism. Nicotine may promote carcinogenesis through activation of extracellular signal-regulated kinase/cyclooxygenase-2/vascular endothelial growth factor signaling pathway.
Purohit
Vishnudutt
V
Division of Metabolism and Health Effects, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 5635 Fishers Lane, Room 2035, Bethesda, MD 20892-9304, USA. vpurohit@mail.nih.gov
Khalsa
Jag
J
Serrano
Jose
J
D000079:Acetaldehyde / Q000378:metabolism; D000428:Alcohol Drinking / Q000009:adverse effects* / Q000453:epidemiology; D000437:Alcoholism / Q000150:complications / Q000209:etiology / Q000235:genetics; D002273:Carcinogens / Q000378:metabolism; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D000431:Ethanol / Q000378:metabolism / Q000633:toxicity*; D006801:Humans; D009369:Neoplasms / Q000453:epidemiology* / Q000235:genetics; D018384:Oxidative Stress / Q000502:physiology
D002273:Carcinogens; D000431:Ethanol; D019392:Cytochrome P-450 CYP2E1; D000079:Acetaldehyde