Acetaldehyde Acetaldehyde is produced by the liver as it breaks down ethanol. The liver then normally eliminates 99% of the acetaldehyde. An average liver can process 7 grams of ethanol per hour. For example, it takes 12 hours to eliminate the ethanol in a bottle of wine, giving 12 hours or more of acetaldehyde exposure. A study of 818 heavy drinkers found that those who are exposed to more acetaldehyde than normal through a defect in the gene for alcohol dehydrogenase are at greater risk of developing cancers of the upper gastrointestinal tract and liver. There are many associations between alcohol drinking and different types of cancer. Data from 2009 indicated 3.5 percent of cancer deaths in the U.S. were due to consumption of alcohol. Reviews In a review, Pöschl and Seitz list some possible mechanisms of alcohol as a carcinogen: * local effects of alcohol * metabolism to acetaldehyde (which may be mutagenic at physiologically meaningful levels) * induction of CYP2E1 * nutritional deficiencies * interactions with retinoids * alcohol and methylation * alcohol and immune surveillance Purohita et al. propose an overlapping list: # production of acetaldehyde, which is a weak mutagen and carcinogen # induction of cytochrome P450 2E1 and associated oxidative stress and conversion of procarcinogens to carcinogens # depletion of S-adenosylmethionine and, consequently, induction of global DNA hypomethylation; # induction of increased production of inhibitory guanine nucleotide regulatory proteins and components of extracellular signal-regulated kinase–mitogen-activated protein kinase signaling # accumulation of iron and associated oxidative stress # inactivation of the tumor suppressor gene BRCA1 and increased estrogen responsiveness (primarily in breast) # impairment of retinoic acid metabolism. Boffetta and Hashibe list plausible mechanisms as including: * a genotoxic effect of acetaldehyde * increased oestrogen concentration * a role as solvent for tobacco carcinogens * production of reactive oxygen species and nitrogen species * changes in folate metabolism 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. Local carcinogenic effect of ethanol 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. Epithelial-mesenchymal transition A study found that alcohol stimulates the epithelial-mesenchymal transition (EMT), in which ordinary cancer cells change into a more aggressive form and begin to spread throughout the body. Effect of alcohol on the progress of cancer when established A study of the influence of alcohol intake on tumor growth of hepatocellular carcinoma (HCC) in patients with type C cirrhosis, found that alcohol influenced tumor volume doubling time (TVDT). A study of chick embryos suggests that alcohol stimulates their tumor growth by fueling the production of a growth factor that stimulates blood vessel development in tumors. A 2006 study in mice showed moderate drinking resulted in larger and stronger tumors via a process known as angiogenesis. A study where high amounts of alcohol were given to mice suggests that it accelerates their cancer growth by speeding up the loss of body fat and depressing immune activity.
Alcohol and cancer
Alcohol and cardiovascular disease
Alcohol and breast cancer
Alcohol and pregnancy
Obesity and cancer
Alcohol and health
Toxic alcohol
Diet and cancer