Total recorded alcohol per capita consumption (15+), in litres of pure alcohol.

Alcohol is associated with an increased risk of a number of cancers. 3.6% of all cancer cases and 3.5% of cancer deaths worldwide are attributable to consumption of alcohol. Breast cancer in women is linked with alcohol intake. Alcohol also increases the risk of cancers of the mouth, esophagus, pharynx and larynx, colorectal cancer, liver cancer, stomach and ovaries.

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Overall mortality from alcohol-related cancers

Australia: A 2009 study found that 2,100 Australians die from alcohol-related cancer each year.

Europe: A 2011 study found that one in 10 of all cancers in men and one in 33 in women were caused by past or current alcohol intake.

Alcohol as a carcinogen and cocarcinogen

The International Agency for Research on Cancer (Centre International de Recherche sur le Cancer) of the World Health Organization has classified alcohol as a Group 1 carcinogen. Its evaluation states, "There is sufficient evidence for the carcinogenicity of alcoholic beverages in humans. …Alcoholic beverages are carcinogenic to humans (Group 1)."

Possible mechanisms of alcohol as a carcinogen

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.

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:

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)

7. 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.

Epithelial-mesenchymal transition

A study found that 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.

Genetic variation and cancer risk

A study found that "the ADH1C*1 allele and genotype ADH1C*1/1 were significantly more frequent in patients with alcohol-related cancers…" A European study has found two gene variants which offer "significant" protection against mouth and throat cancers. Alcohol is a known porphyrinogenic chemical. Several European studies have linked the inherited hepatic porphyrias with a predisposition to hepatocellular carcinoma. Typical risk factors for HCC need not be present with the acute hepatic porphyrias, specifically acute intermittent porphyria, variegate porphyria and hereditary coproporphyria. Porphyria cutanea tarda is also associated with HCC, but with typical risk factors including evidence of hepatotropic viruses, hemochromatosis and alcoholic cirrhosis. Tyrosinemia Type I, an inherited disorder in tyrosine metabolism impacting the second enzyme in the heme metabolic pathway is associated with a high risk of developing HCC in younger populations, including children.

Alcohol as a risk factor for specific cancers

Moderate alcohol consumption increases risk

A study found that, "Increasing but moderate alcohol consumption in women was determined to be associated with an increased risk of cancers of the oral cavity and pharynx, esophagus, larynx, rectum, breast, and liver…"