Mechanisms of alcohol-associated cancers: introduction and summary of the symposium

Abstract

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.

CYP2E1 RsaIpolymorphism impacts on risk of colorectal cancer association with smoking and alcohol drinking

“…We found alcohol drinking to significantly increase risk of cancer development, especially in the rectum, and there was a significant interaction with the CYP2E1 RsaⅠc2/c2 genotype in both the colon and rectum. Our results are consistent with previous investigations indicating that alcohol consumption is associated with an increased risk for cancers of many organs, such as oral cavity, pharynx, larynx, esophagus, breast, liver, ovary; colon, rectum, stomach and pancreas [42] . Chronic ethanol consumption may promote carcinogenesis by (1) production of acetaldehyde, which is a weak mutagen and carcinogen; (2) induction of CYP2E1 and associated oxidative stress and conversion of pro-carcinogens 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 [43] .…”

Etiology of non-B non-C hepatocellular carcinoma in the eastern district of Tokyo

“…Habitual alcohol drinking in these patients may induce the retention of acetaldehyde, which is known to be a particularly toxic and carcinogenic chemical. 31 Thus, a relatively small amount of alcohol drinking may lead to the development of non-B non-C HCC in the Asian population, including the Japanese population. Furthermore, NAFLD has been widely accepted as a possible etiological factor in the development of non-B non-C HCC; the fact that DM is common in NAFLD patients may further facilitate the development of HCC.…”

Hepatocellular carcinoma in Japanese patients with nonalcoholic fatty liver disease, alcoholic liver disease, and chronic liver disease of unknown etiology: report of the nationwide survey

“…Alcohol may be a potent carcinogen, even when its intake is low [11]. To investigate the pathogenesis of unknown HCC, the influence of obesity was investigated, as well as the effect of lifestyle diseases and no to modest alcohol intake (below the Japanese criterion for alcoholic liver disease of 70 g/day).…”