Alcohol and cancer
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.
Australia: A 2009 study found that 2,100 Australians die from alcohol-related cancer each year.
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 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.
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.
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 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…"
Cancers of the mouth, esophagus, pharynx, and larynx
Alcohol is a risk factor for cancers of the mouth, esophagus, pharynx and larynx. The U.S. National Cancer Institute states "Drinking alcohol increases the risk of cancers of the mouth, esophagus, pharynx, larynx, and liver in men and women, … In general, these risks increase after about one daily drink for women and two daily drinks for men. (A drink is defined as 12 ounces of regular beer, 5 ounces of wine, or 1.5 ounces of 80-proof liquor.) … Also, using alcohol with tobacco is riskier than using either one alone, because it further increases the chances of getting cancers of the mouth, throat, and esophagus."
The International Head and Neck Cancer Epidemiology (INHANCE) Consortium co-ordinated a meta-study on the issue. A study looking at laryngeal cancer and beverage type concluded, "This study thus indicates that in the Italian population characterized by frequent wine consumption, wine is the beverage most strongly related to the risk of laryngeal cancer."
A review of the epidemiological literature published from 1966 to 2006 concluded that:
- The risk of esophageal cancer nearly doubled in the first two years following alcohol cessation, a sharp increase that may be due to the fact that some people only stop drinking when they are already experiencing disease symptoms. However, risk then decreased rapidly and significantly after longer periods of abstention.
- Risk of head and neck cancer only reduced significantly after 10 years of cessation.
- After more than 20 years of alcohol cessation, the risks for both cancers were similar to those seen in people who never drank alcohol.
A study concluded that for every additional drink regularly consumed per day, the incidence of oral cavity and pharynx cancers increases by 1 per 1000. The incidence of cancers of the esophagus and larynx increase by 0.7 per 1000.
A woman drinking an average of two units of alcohol per day has an 8% higher risk of developing breast cancer than a woman who drinks an average of one unit of alcohol per day. A study concluded that for every additional drink regularly consumed per day, the incidence of breast cancer increases by 11 per 1000. Approximately 6% (between 3.2% and 8.8%) of breast cancers reported in the UK each year could be prevented if drinking was reduced to a very low level (i.e. less than 1 unit/week).
The National Institutes of Health, the National Cancer Institute, Cancer Research, the American Cancer Society, the Mayo Clinic, and the Colorectal Cancer Coalition, American Society of Clinical Oncology and the Memorial Sloan-Kettering Cancer Center list alcohol as a risk factor.
A WCRF panel report finds the evidence "convincing" that alcoholic drinks increase the risk of colorectal cancer in men at consumption levels above 30 grams of absolute alcohol daily. The National Cancer Institute states, "Heavy alcohol use may also increase the risk of colorectal cancer"
One study found that "While there was a more than twofold increased risk of significant colorectal neoplasia in people who drink spirits and beer, people who drank wine had a lower risk. In our sample, people who drank more than eight servings of beer or spirits per week had at least a one in five chance of having significant colorectal neoplasia detected by screening colonoscopy.".
The EPIC study suggests that "people who drink 15 grams of alcohol a day– equivalent to about two units– have about a 10 percent increased risk of bowel cancer. Those who drank more than 30 grams of alcohol– equivalent to three to four units which is less than a couple of pints of strong lager– increased their bowel cancer risk by around 25 per cent."
A study found, "The proportion of patients with adenomas was 29.6% in abstainers, 22.1% in moderate drinkers, and 36.7% in heavy drinkers." It concluded "Consumption of less than seven alcohol drinks per week does not increase the risk of having a colorectal adenoma. We found evidence in this study that moderate alcohol consumption among long-term smokers may potentially decrease the risk of an adenoma compared to abstainers."
A Japanese study concluded, "One fourth of colorectal cancer cases in men were attributable to an alcohol intake of ≥23 g/day."
A study concluded that for every additional drink regularly consumed per day, the incidence of rectal cancer increases by 1 per 1000.
"Approximately 5 percent of people with cirrhosis develop liver cancer. Cirrhosis is a disease that develops when liver cells are replaced with scar tissue after damage from alcohol abuse, …"
The NIAAA reports that "Prolonged, heavy drinking has been associated in many cases with primary liver cancer." However, it is liver cirrhosis, whether caused by alcohol or another factor, that is thought to induce the cancer."
"The chances of getting liver cancer increase markedly with five or more drinks per day" (NCI).
A study concluded that for every additional drink regularly consumed per day, the incidence of liver cancer increases by 0.7 per 1000.
In the United States, liver cancer is relatively uncommon, afflicting approximately 2 people per 100,000, but excessive alcohol consumption is linked to as many as 36% of these cases by some investigators "Overall, 61% of HCC were attributable to HCV [hepatitis C virus], 13% to HBV [hepatitis B virus], and 18% to heavy alcohol drinking." A study in the province of Brescia, northern Italy concluded, "On the basis of population attributable risks (AR), heavy alcohol intake seems to be the single most relevant cause of HCC in this area (AR: 45%), followed by HCV (AR: 36%), and HBV (AR: 22%) infection."
Alcohol intake of more than 2 drinks per day is associated with a small increased risk of lung cancer. Commenting on a study by Freudenheim et al., R. Curtis Ellison MD writes, "This study, like others, suggests a weak, positive association between consuming larger amounts of alcohol (>2 drinks a day) and lung cancer risk."
"Statistically significant increases in risk also existed for cancers of the stomach, colon, rectum, liver, female breast, and ovaries."
"While alcohol has been extensively studied as a cause of stomach cancer there is no conclusive evidence that it increases risk. However, results from at least three studies suggest that heavy alcohol consumption may increase the risk of stomach cancer in heavy smokers."
A Taiwanese study concluded, "…cigarette smoking may play the most harmful role in the initial development of gastric cancer, and that drinking alcohol may promote the process."
A Norwegian study found that, "No statistically significant associations between various degrees of exposure to alcohol and risk of gastric cancer was revealed, but combined high use of cigarettes (>20/day) and alcohol (>5 occasions/14 days) increased the risk of noncardia gastric cancer nearly 5-fold (HR = 4.90 [95% CI = 1.90–12.62]), compared to nonusers."
Alcohol consumption of 50g or more per day increases risk
Alcohol has been identified as a risk factor for endometrial cancer. Data however, on the association of alcohol intake and endometrial cancer is conflicting. Where data exists for an association low to moderate intake of alcohol, (less than two drinks per day) is not associated with an increased risk but an association has been suggested for higher alcohol intake. "Our results suggest that only alcohol consumption equivalent to 2 or more drinks per day increases risk of endometrial cancer in postmenopausal women." "In conclusion, our results suggest that low alcohol consumption (up to one drink per day) is unlikely to substantially influence risk of endometrial cancer."
Alcohol has been suggested as a risk factor for gall bladder cancer. Evidence suggests that a high intake of alcohol is associated with gall bladder cancer. Men may be at a higher risk of alcohol-related gallbladder cancer than women.
"Thus, the results of this study suggest that relatively elevated alcohol intake (of the order of 40 g per day or more) may cause a modest increase of epithelial ovarian cancer risk.". "Associations were also found between alcohol consumption and cancers of the ovary and prostate, but only for 50 g and 100 g a day." "Statistically significant increases in risk also existed for cancers of the stomach, colon, rectum, liver, female breast, and ovaries."
"Thus, this pooled analysis does not provide support for an association between moderate alcohol intake and ovarian cancer risk."
"Data from the Health Professionals Follow-Up Study showed only a weak association between overall alcohol intake and prostate cancer risk, and no association at all between red wine intake and prostate cancer risk."
A meta-analysis published in 2001 found a small but significant increased risk for men drinking more than 50 g/day of alcohol, with a slightly higher risk for men consuming more than 100 g/day. Since that analysis, cohort studies in America have found increased risks for men drinking moderate amounts of spirits, and for ‘binge drinkers, but moderate consumption of beer or wine has not been linked to an increased risk.
Alcohol consumption of 50 g and 100 g per day is also associated with cancers of the ovary and prostate. However, one study concludes, that moderate alcohol consumption increases the risk of prostate cancer. Liquor, but not wine or beer, consumption was positively associated with prostate cancer."
The Fred Hutchinson Cancer Research Center found that men who consumed four or more glasses of red wine per week had a 50 percent reduction in the risk of developing prostate cancer. They "found no significant effects – positive nor negative – associated with the consumption of beer or hard liquor and no consistent risk reduction with white wine, which suggests that there must be a beneficial compound in red wine that other types of alcohol lack. That compound … may be an antioxidant called resveratrol, which is abundant in the skins of red grapes.".
Small intestine cancer
A study of small intestine cancer patients reported that alcohol consumption was associated with adenocarcinomas and malignant carcinoid tumors.
"In men and women combined, a significant 3-fold increased risk in heavy drinkers (80+g ethanol/day) relative to more moderate drinkers and non-drinkers was observed."
"Alcohol and tobacco consumption did not increase the risk of adenocarcinoma of the small intestine. … While the present data are inconsistent with a major effect of tobacco or alcohol, a moderate association between these factors and small bowel cancer may have been obscured by the play of chance."
Evidence of alcohol as a risk factor is mixed
Intake of alcohol during pregnancy has been associated with childhood leukemia. A review published by the National Cancer Institute placed maternal alcohol consumption during pregnancy in the category of "suggestive" but concluded that the risk was not important.
- Acute Lymphocytic Leukemia (ALL)
For ALL in children, maternal alcohol consumption during pregnancy is "unlikely to be an important risk factor for ALL"
- Acute myeloid leukemia (AML)
A study concluded, "In conclusion, even though our study did not show a clear association between alcohol intake and leukemia risk, some of the patterns of the risk estimates (a possible J-shaped dose-response curve between alcohol intake and ALL, AML, and CLL risks, and the positive association between alcohol and CML), may be suggestive."
- Childhood AML
"Three studies have reported an increased risk (approximately 1.5-2 fold) in mothers who drank alcoholic beverages during pregnancy. These associations have been particularly apparent in children diagnosed younger than three years of age.". "Maternal alcohol consumption during pregnancy increases the risk of infant leukemia, especially AML."
- Acute non-lymphocytic leukemia (ANLL)
A study found that intrauterine exposure to alcohol doubled the risk for childhood ANLL.
- Chronic Lymphocytic Leukemia (CLL)
A study concluded, "In conclusion, even though our study did not show a clear association between alcohol intake and leukemia risk, some of the patterns of the risk estimates (a possible J-shaped dose-response curve between alcohol intake and ALL, AML, and CLL risks, and the positive association between alcohol and CML), may be suggestive."
- Chronic myeloid leukemia (CML)
A population-based case-control study in Italy found a non-significant positive association between drinking and CML.
- Hairy cell leukemia
A study concluded, "There was no association found for cigarette smoking, alcohol or coffee consumption and hairy cell leukemia."
Multiple myeloma (MM)
"About 7 out of 10 cases of chronic pancreatitis are due to long term heavy drinking. Chronic pancreatitis is a known risk factor for cancer of the pancreas. But chronic pancreatitis that is due to alcohol doesn't increase risk as much as other types of chronic pancreatitis. So if there is a link with alcohol and pancreatic cancer risk, it is only very slight."
Whilst the association between alcohol abuse and pancreatitis is well established the association between alcohol consumption and pancreatic cancer is less clear. Overall the evidence suggests a slightly increased risk of pancreatic cancer with chronic heavy alcohol consumption but the evidence remains conflicting with a number of studies finding no association., but no increased risk for people consuming up to 30g of alcohol a day
"Our findings indicate that alcohol drinking at the levels typically consumed by the general population of the United States is probably not a risk factor for pancreatic cancer. Our data suggest, however, that heavy alcohol drinking may be related to pancreatic cancer risk."
"Relative risks of pancreatic cancer increased with the amount of alcohol consumed (Ptrend = 0.11) after adjustment for age, smoking status, and pack-years of smoking."
"Alcoholics had only a modest 40% excess risk of pancreatic cancer … The excess risk for pancreatic cancer among alcoholics is small and could conceivably be attributed to confounding by smoking."
"It was shown that the relative risk of cancer of the pancreas increases with fat and alcohol intakes, … Alcohol may be not directly involved in the aetiology of cancer of the pancreas: its effect could be due to the contents of some alcoholic beverages."
"When compared with data from non-drinkers, the cumulative lifetime consumption of all types of alcohol in grams of ethanol… beer, spirits, red wine and fortified wine was not related to risk. The consumption of white wine was inversely associated with risk…. The uniformly reduced risk estimates for the lifetime number of drinks of white wine were based on small numbers…."
"For the most part, consumption of total alcohol, wine, liquor and beer was not associated with pancreatic cancer."
"Data from these two large cohorts do not support any overall association between coffee intake or alcohol intake and risk of pancreatic cancer."
"Our findings are consistent with a modest increase in risk of pancreatic cancer with consumption of 30 or more grams of alcohol per day."
Alcohol consumption is not suspected to increase risk
This section lists cancers where alcohol is not listed as a risk factor and where papers have been published.
A study concluded that feotal exposure to alcohol is not associated with childhood astrocytoma.
Bile duct cancer
"Epidemiological data on alcohol drinking and bladder cancer are suggestive of no association, although findings were not always consistent. For both habits, an explanation of the moderate increase in risk observed in some investigations might be attributed to residual confounding by smoking, or to an association between alcohol, coffee, and yet unidentified risk factors for bladder cancer."
A study concluded "that alcoholic women are at high risk for in situ and invasive cervical cancer" but attributed this to indirect, lifestyle-related reasons.
Ductal carcinoma in situ (DCIS) breast cancer
"DCIS patients and control subjects did not differ with respect to oral contraceptive use, hormone replacement therapy, alcohol consumption or smoking history, or breast self-examination. Associations for LCIS were similar."
Intraocular and uveal melanomas
A study found no association between alcohol and uveal melanoma.
Nasopharynageal cancer / Nasopharyngeal carcinoma (NPC)
Alcohol intake has been associated with an increased risk of developing neuroblastoma.
Salivary gland cancer (SGC)
Alcohol use is associated with an increased risk of salivary gland cancer.
A review concluded that "There is no firm evidence of a causal relation between behavior risks [tobacco, alcohol and diet] and testicular cancer."
A 2009 review found that alcohol intake does not affect the risk of developing thyroid cancer. However, a 2009 study of 490,000 men and women concluded that alcohol may reduce the risk of thyroid cancer. A 2009 study of 1,280,296 women in the United Kingdom concluded, "The decreased risk for thyroid cancer that we find to be associated with alcohol intake is consistent with results from some studies, although a meta-analysis of 10 case–control studies and two other cohort studies reported no statistically significant associations."
A Danish study found that "Abstinence from alcohol consumption was associated with low risk for both VV-SCCvagina and VV-SCCvulva in our study."
A study concluded that alcoholic women are at high risk for cancer of the vagina. In both studies, indirect, lifestyle-related reasons were cited.
One study reported "No consistent association emerged between milk, meat, liver, alcohol and coffee consumption and risk of vulvar cancer." A Danish study found the reverse, that alcohol consumption is significantly associated with VV-SCCvagina and VV-SCCvulva cancer. A Swedish study concluded that alcoholic women are at no higher risk for cancer of the vulva.
Alcohol consumption might reduce risk
Hodgkin's lymphoma (HL)
A study concluded, "The results of this large-scale European study … suggested a protective effect of alcohol on development of NHL for men and in non-Mediterranean countries." A population based case-control study in Germany found that alcohol reduced the risk of HL for both men and women but more so for men, whose risk was lowered by 53%.
A population-based case-control study in Italy reported a protective effect of alcohol consumption on risk of HL among non-smokers. Analysis of data from a series of case-control studies in Northern Italy revealed a modest positive effect of alcohol on lowering risk of HL among both smokers and non-smokers.
Kidney cancer (Renal cell carcinoma) (RCC)
"Moderate alcohol consumption was associated with a lower risk of renal cell cancer among both women and men in this pooled analysis" "This pooled analysis found an inverse association between alcohol drinking and RCC. Risks continued to decrease even above eight drinks per day (i.e. >100 g/day) of alcohol intake, with no apparent levelling in risk."
A study concluded, "Results from our prospective cohort study of middle-aged and elderly women indicate that moderate alcohol consumption may be associated with decreased risk of RCC." Researchers who conducted a study in Iowa reported that "In this population-based case-control investigation, we report further evidence that alcohol consumption decreases the risk of RCC among women but not among men. Our ability to show that the association remains after multivariate adjustment for several new confounding factors (i.e., diet, physical activity, and family history) strengthens support for a true association.
Another study found no relationship between alcohol consumption and risk of kidney cancer among either men or women.
A Finnish study concluded, "These data suggest that alcohol consumption is associated with decreased risk of RCC in male smokers. Because most of the risk reductions were seen at the highest quartile of alcohol intake and alcohol is a risk factor for a number of cancers particularly among smokers, these data should be interpreted with caution." "Our data suggest an inverse association between alcohol intake and risk of renal cell cancer…" Compared with nondrinkers, men who drank one or more drinks per day had a 31% lower risk of kidney cancer among 161,126 Hawaii-Los Angeles Multiethnic Cohort participants.
Non-Hodgkin lymphoma (NHL)
A study concluded, "People who drink alcoholic beverages might have a lower risk of NHL than those who do not, and this risk might vary by NHL subtype." "Compared with nondrinkers, alcohol consumers had a lower risk for non-Hodgkin's lymphoma overall … and for its main subtypes." A study concluded, "Nonusers of alcohol had an elevated NHL risk compared with users…"
Some studies have found a protective effect on NHL of drinking some forms of alcoholic beverage or in some demographic groups. A study of men in the US found that consumption of wine, but not beer or spirits, was associated with a reduced NHL risk and a large European study found a protective effect of alcohol among men and in non-Mediterranean countries.." A study of older women in Iowa found alcohol to reduce the risk of NHL and the amount of alcohol consumed, rather than the type of alcoholic beverages, appeared to be the main determinant in reducing risk." A possible mechanism has been suggested.
Some studies have not found a protective effect from drinking. British research found no association between frequency of drinking and NHL and research in Sweden found that total beer, wine, or liquor intake was not associated with any major subtype of NHL examined, apart from an association between high wine consumption and increased risk of chronic lymphocytic leukemia.."
One study of NHL patients concluded, "Our findings strongly encourage physicians to advise NHL patients to stop smoking and diminish alcohol consumption to obtain improvements in the course of NHL."
Recommended maximum alcohol intake
As outlined above, there is no recommended alcohol intake with respect to cancer risk alone as it varies with each individual cancer. See Recommended maximum intake of alcoholic beverages for a list of governments' guidances on alcohol intake which, for a healthy man, range from 140–280g per week.
One meta-analysis suggests that risks of cancers may start below the recommended levels. "Risk increased significantly for drinkers, compared with non-drinkers, beginning at an intake of 25 g (< 2 standard drinks) per day for the following: cancers of the oral cavity and pharynx (relative risk, RR, 1.9), esophagus (RR 1.4), larynx (RR 1.4), breast (RR 1.3), liver (RR 1.2), colon (RR 1.1), and rectum (RR 1.1)"
World Cancer Research Fund recommends that people aim to limit consumption to two drinks a day for a man and one for a woman. It defines a "drink" as containing about 10–15 grams of ethanol.
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