title: Alcohol, DNA methylation, and cancer.
abstract: Cancer is one of the most significant diseases associated with chronic alcohol consumption, and chronic drinking is a strong risk factor for cancer, particularly of the upper aerodigestive tract, liver, colorectum, and breast. Several factors contribute to alcohol-induced cancer development (i.e., carcinogenesis), including the actions of acetaldehyde, the first and primary metabolite of ethanol, and oxidative stress. However, increasing evidence suggests that aberrant patterns of DNA methylation, an important epigenetic mechanism of transcriptional control, also could be part of the pathogenetic mechanisms that lead to alcohol-induced cancer development. The effects of alcohol on global and local DNA methylation patterns likely are mediated by its ability to interfere with the availability of the principal biological methyl donor, S-adenosylmethionine (SAMe), as well as pathways related to it. Several mechanisms may mediate the effects of alcohol on DNA methylation, including reduced folate levels and inhibition of key enzymes in one-carbon metabolism that ultimately lead to lower SAMe levels, as well as inhibition of activity and expression of enzymes involved in DNA methylation (i.e., DNA methyltransferases). Finally, variations (i.e., polymorphisms) of several genes involved in one-carbon metabolism also modulate the risk of alcohol-associated carcinogenesis.
authors: Centro de Investigación Cooperative en Biosciencias (CIC bioGUNE), Technology Park of Bizkaia, Derio, Spain.
authors: Marta
authors: M
authors: Varela-Rey
authors: Ashwin
authors: A
authors: Woodhoo
authors: Maria-Luz
authors: ML
authors: Martinez-Chantar
authors: José M
authors: JM
authors: Mato
authors: Shelly C
authors: SC
authors: Lu
mesh_terms: D000428:Alcohol Drinking; D000437:Alcoholism; D001943:Breast Neoplasms / Q000235:genetics; D063646:Carcinogenesis / Q000139:chemically induced* / Q000235:genetics; D002492:Central Nervous System Depressants / Q000009:adverse effects* / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics; D044127:Epigenesis, Genetic / Q000187:drug effects*; D000431:Ethanol / Q000009:adverse effects* / Q000378:metabolism; D005260:Female; D006258:Head and Neck Neoplasms / Q000235:genetics; D006801:Humans; D009369:Neoplasms / Q000235:genetics*
chemical_list: D002492:Central Nervous System Depressants; D000431:Ethanol