<Li> production of reactive oxygen species and nitrogen species </Li> <Li> changes in folate metabolism </Li> <P> Individuals who both smoke and drink are at a much higher risk of developing mouth, tracheal, and esophageal cancer . Research has shown their risk of developing these cancers is 35 times higher than in individuals who neither smoke nor drink . This evidence may suggest that there is a cocarcinogenic interaction between alcohol and tobacco - related carcinogens . </P> <P> The risk of cancer associated with alcohol consumption is higher in tissues in closest contact on ingestion of alcohol, such as the oral cavity, pharynx and esophagus . This is explained by the fact that ethanol is a proven mutagen and in addition, metabolite of ethanol (acetaldehyde) produced in the liver is highly carcinogenic, thus explaining both local (mouth, throat, esophageal cancers) as well as distant (skin, liver, breast) cancers . It is well known that ethanol causes cell death at the concentrations present in alcoholic beverages . Few cells survive a one - hour exposure to 5 - 10% ethanol or a 15 - second exposure to 30--40% ethanol in cell culture, where surviving cells might undergo genomic changes leading to carcinogenesis . But recent evidence suggests that the cytotoxic effect of ethanol on the cells lining the oral cavity, pharynx and esophagus activates the division of the stem cells located in deeper layers of the mucosa to replace the dead cells . Every time stem cells divide, they become exposed to unavoidable errors associated with cell division (e.g., mutations arising during DNA replication and chromosomal alterations occurring during mitosis) and also become highly vulnerable to the genotoxic activity of DNA - damaging agents (e.g., acetaldehyde and tobacco carcinogens). Alcohol consumption probably increases the risk of developing cancer of the oral cavity, pharynx and esophagus by promoting the accumulation of cell divisions in the stem cells that maintain these tissues in homeostasis . Because the cytotoxic activity of ethanol is concentration - dependent, the risk of these cancers will not only increase with increasing amounts of ethanol, but also with increasing concentrations; an ounce of whisky is probably more carcinogenic when taken undiluted than when taken mixed with non-alcoholic beverages . The local cytotoxic effect of ethanol may also explain the known synergistic effect of alcohol and tobacco use on the risk of these cancers . </P>

World health organization declared alcohol a group 1 carcinogen