Alcohol and cancer have a complex relationship. Alcohol causes cancers of the oesophagus, liver, breast, colon, oral cavity, rectum, pharynx, and larynx, and probably causes cancers of the pancreas. Cancer risk can occur even with light to moderate drinking. The more alcohol is consumed, the higher the cancer risk, and no amount can be considered completely safe.
Alcoholic beverages were classified as a group 1 carcinogen by the International Agency for Research on Cancer (IARC) in 1988. An estimated 3.6% of all cancer cases and 3.5% of cancer deaths worldwide are attributable to consumption of alcohol (more specifically, acetaldehyde, a metabolic derivative of ethanol). 740,000 cases of cancer in 2020 or 4.1% of new cancer cases were attributed to alcohol.
Alcohol is thought to cause cancer through three main mechanisms: (1) DNA methylation, (2) oxidative stress, and (3) hormonal alteration. Additional mechanisms include microbiome dysbiosis, reduced immune system function, retinoid metabolism, increased levels of inflammation, 1-carbon metabolism and disruption of folate absorption.
Heavy drinking consisting of 15 or more drinks per week for men or 8 or more drinks per week for women contributed the most to cancer incidence compared with moderate drinking. The rate of alcohol related cases is 3:1 male:female, especially in oesophageal and liver cancers. Some nations have introduced alcohol packaging warning messages that inform consumers about alcohol and cancer. The alcohol industry has tried to actively mislead the public about the risk of cancer due to alcohol consumption, in addition to campaigning to remove laws that require alcoholic beverages to have cancer warning labels.
Epidemiology
Cancers attributed to alcohol In 2020, approximately 740,000 cases of alcohol-related cancers were identified globally with
58% of cases (430,000) residing in Asia 25% of cases (180,000) residing in Europe 8% of cases (60,000) residing in North America 5% of cases (39,000) residing in Latin America and the Caribbean 3% of cases (23,000) residing in Africa 1% of cases (7,000) residing in regions termed "other."
More than three-quarters of the 740,000 cases were in men.
United States In the United States of America, alcohol-related cancer rates were highest in the following states: Delaware, Colorado, Washington, D.C., New Hampshire, and Alaska. Conversely, alcohol-related cancer rates were lowest in the following states: Kentucky, Arizona, Oklahoma, West Virginia, and Utah.
From 2013 to 2016, approximately 19,000 (4%) cancer-related deaths in the United States were attributed to alcohol consumption each year, with breast cancer and esophageal cancer deaths being the most common in women and men respectively.
An estimated 3.2% of cancer deaths in United States were attributed to alcohol consumption. The distribution of mortality by state were consistent with the distribution of incident cases. According to, Vivek Murthy, the Surgeon General of the United States, alcohol ranked third among preventable causes of cancer after tobacco and obesity.
Europe Approximately 10% and 3% of cancer diagnoses in European men and women respectively are attributed to alcohol consumption.
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.
Australia A 2009 study found that 2,100 Australians die from alcohol-related cancer each year.
Alcohol as a carcinogen and co-carcinogen In 1998, the International Agency for Research on Cancer (Centre International de Recherche sur le Cancer) of the World Health Organization classified alcoholic beverages as a carcinogen. Its evaluation states:
After more epidemiological evidence connecting alcohol and cancers became available, the IARC reconvened in 2007. Based on epidemiological studies, which revealed cancer risk was independent of the type of alcohol, and animal studies, which showed increased cancer risk with exposure to ethanol alone, the group determined that the ethanol in alcoholic beverages was carcinogenic to humans. Alcohol was determined to increase the risk of developing breast cancer, liver cancer, colorectal cancer, esophageal cancers, pharyngeal cancer, laryngeal cancer, and oral cancer. In 2009, the group determined that acetaldehyde which is a metabolite of ethanol is also carcinogenic to humans.
The U.S. Department of Health & Human Services' National Toxicology Program (NTP) classified alcoholic beverages as a "known human carcinogen" in their 2000 Report on Carcinogens,National Toxicology Program Alcoholic Beverage Consumption: Known to be a human carcinogen First listed in the Ninth Report on Carcinogens (2000)(PDF) and this classification remains current as of the 15th edition published in 2021. While the report distinguishes between the beverage itself and acetaldehyde (a byproduct of alcohol metabolism), classifying the latter as "reasonably anticipated to be a human carcinogen," the overall message is clear: consuming alcoholic drinks poses a cancer risk.
A 2001 systematic review did not find a clear safe level of alcohol consumption where there is no increased risk of cancer.
Mechanisms
Acetaldehyde Alcohol metabolism generates genotoxic acetaldehyde and reactive oxygen species. The possible mechanisms for its carcinogenicity include formation of the possible mutagen acetaldehyde, and the induction of the cytochrome P450 system which is known to produce mutagenic compounds from promutagens.
Acetaldehyde is a byproduct of ethanol breakdown in the liver, metabolized by alcohol dehydrogenase (ADH), cytochrome P-450 2E1 and bacterial catalases. The liver then normally eliminates 99% of the acetaldehyde. ALDH2 converts Acetaldehyde into acetate which is a byproduct that can be excreted through the liver. Those with ADH1B*1 have higher rates of conversion of ethanol into acetaldehyde while, people with ALDH2*2 have a slower conversion rate of acetaldehyde to acetate causing faster build up of acetaldehyde concentrations. 28-45% of east Asian populations carry the ALDH2*2 allele. 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.
The acetaldehyde motif can bind DNA to alter its physical shape or block repair and synthesis mechanisms to induce mutations, breaks and exchanges. Acetaldehyde and ethanol both inhibit S-adenosyl-L-methiodine (SAMe) synthesis which is a methyl group transferase.
DNA methylation DNA methylation is the addition of a methyl group to the carbon-5 of nucleotides. The most common methylation site is onto a cystine preceding guanine nucleotides. This methylation is catalyzed by DNA methyltransferase enzymes taking a methyl group from SAMe. Heavy alcohol consumption is thought to cause epigenetic changes by decreasing the availability of SAMe thereby changing the methylation pattern of DNA causing hypo or hypermethylation resulting in alteration of DNA transcription.
Oxidative stress Oxidative stress and reactive oxygen species (ROS) accumulation is a major player in cancer growth. the metabolism of ethanol by CYP450 2E1 into acetaldehyde has a byproduct of ROS. The presence of ROS in the cellular environment causes lipid peroxidation which can lead to exocyclic adducts. ROS in a tumor microenvironment can also act as an intercellular signal leading to up-regulation of vascular endothelial growth factors and monocyte chemotactic protein-1. The accumulation of iron is also found to correlate to alcohol consumption which leads to higher levels of peroxidation and resulting oxidative damage.
Polycyclic aromatic hydrocarbons Polycyclic aromatic hydrocarbons also play a role in alcohol-induced carcinogenesis. Exposure occurs through drinking alcohol aged in charred barrels, flavored with peat smoke, or made with roasted grains.
Hormonal regulation High levels of hormones in serum have been associated with heavy alcohol use. Especially estrogen and estradiol which can increase transcriptional activity in ER+ cells which promote cell proliferation. Those in pre-menopause using progestin contraceptives have some compensation for the high levels of estradiol, though after menopause those with heavy alcohol consumption have higher risk for breast cancer and estrogen-dependent cancers.
Other mechanisms Additional mechanisms contribute to cancer risk with alcohol consumption. It is thought that heavy alcohol consumption can cause a decrease in folic acid availability which can decrease the availability of nucleotides for DNA repair. Additionally ethanol can decrease the conversion of homocysteine to methionine which is an essential amino acid that is part of the formation of SAMe.
Increased inflammation due to alcohol consumption can increase various cytokine formations especially NF-κB which is a transcription factor.
Additionally alcohol usage is associated with lower Vitamin A levels which causes a reduction in retinoid conversion and signaling.
Individuals who both smoke and drink are at a much higher risk of developing mouth, tracheal, and esophageal cancer. Ethanol is thought to potentially be a solvent for carcinogenic factors in smoking. 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 carcinogen 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