Alcohol and cancer

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

"Considerable evidence suggests a connection between heavy alcohol consumption and increased risk for cancer, with an estimated 2 to 4 percent of all cancer cases thought to be caused either directly or indirectly by alcohol[1]" indicates the NIAAA.[2]" 3.6% of all cancer cases worldwide are related to alcohol drinking, resulting in 3.5% of all cancer deaths."[3]

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)."[4]

The U.S. National Institute on Alcohol Abuse and Alcoholism (NIAAA) reports that "Although there is no evidence that alcohol itself is a carcinogen, alcohol may act as a cocarcinogen by enhancing the carcinogenic effects of other chemicals. For example, studies indicate that alcohol enhances tobacco's ability to stimulate tumor formation in rats.[5] In humans, the risk for mouth, tracheal, and esophageal cancer is 35 times greater for people who both smoke and drink than for people who neither smoke nor drink,[6] implying a cocarcinogenic interaction between alcohol and tobacco-related carcinogens."[2]

The NIAAA emphasizes that "Although epidemiologic studies have found a clear association between alcohol consumption and development of certain types of cancer, study findings are often inconsistent and may vary by country and by type of cancer."[2]

"Studies have suggested that high concentrations of acetaldehyde, which is produced as the body breaks down ethanol, could damage DNA in healthy cells. … Researchers at the National Institute on Alcohol Abuse and Alcoholism in Bethesda, Maryland, have added weight to this idea by showing that the damage occurs at concentrations of acetaldehyde similar to those in saliva and the gastrointestinal tract while people drink alcohol. Acetaldehyde appears to react with polyamines - naturally occurring compounds essential for cell growth - to create a particularly dangerous type of mutagenic DNA base called a Cr-Pdg adduct…"[7]

Alcohol as risk factor for cancers

Alcohol is a risk factor for these cancers

Head and neck cancers

Head and neck cancers are a collective term for cancers of the:

The U.S. National Cancer Institute's (NCI) Cancer Trends Progress Report Alcohol Consumption states that drinking alcohol increases the risk of these cancers in both men and women. In general, these risks increase above the recommended maximum intake (see below). "Heavy alcohol use … leads to greater increases in risk for most of the alcohol-related cancers. … 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-ordinates research on this topic – see Pooled analysis investigating the effects of beer, wine and liquor consumption on the risk of head and neck cancers.

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."[8]

The American Cancer Society estimates that, as a proportion of all cancer deaths in the US in 2006, cancer of the mouth (oral cavity) will represent 1.3 percent, of the esophagus will be 2.4 percent, of the pharynx will constitute slightly under one-half of one percent, and of the larynx will be about six-tenths of one percent.[9]

Although they are also located in the head or neck, alcohol consumption is not a risk factor for brain cancer, eye cancer, pituitary gland cancer, thymus cancer, salivary gland cancer, thyroid cancer, nasal cavity and paranasal sinus cancer, or adenoid cancer. (see below).

Breast cancer

Alcohol increases the risk of breast cancer in women. A review concludes that "studies confirm previous observations that there appears to be an association between alcohol intake and increased risk of breast cancer in women. On balance, there was a weak association between the amount of alcohol consumed and the relative risk."[10]

The National Institute on Alcohol Abuse and Alcoholism (NIAAA) concludes that "Chronic alcohol consumption has been associated with a small (averaging 10 percent) increase in a woman's risk of breast cancer[11][12] .[13] According to these studies, the risk appears to increase as the quantity and duration of alcohol consumption increases. Other studies, however, have found no evidence of such a link[14][15][16] .[2] " The nature and inconsistency of the evidence has called into question the existence of any causal link between moderate alcohol consumption and breast cancer [2]

The Committee on Carcinogenicity of Chemicals in Food, Consumer Products concludes, "The new research estimates that a woman drinking an average of two units of alcohol per day has a lifetime risk of developing breast cancer 8% higher than a woman who drinks an average of one unit of alcohol per day. The risk of breast cancer further increases with each additional drink consumed per day. … The research also concludes that 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)."[17]

It has been reported that "Two drinks daily increase the risk of getting breast cancer by about 25 percent." (NCI) but the evidence is inconsistent. The Framingham study has tracked individuals since the 1940s. Data from that research found that drinking alcohol moderately did not increase breast cancer risk.[18] Similarly, research by the Danish National Institute for Public Health found that moderate drinking had virtually no effect on breast cancer risk.[19] Breast cancer constitutes about 7.3% of all cancers.[9] Among women, breast cancer comprises 60% of alcohol-attributable cancers.[20] One study suggests that women who frequently drink red wine may have an increased risk of developing breast cancer.[21]

Alcohol consumption has been shown to increase the rate of breast cancer in women.[22]

A study of 17,647 nurses found that high drinking levels more than doubled risk of breast cancer. "The relative risk of breast cancer was 2.30 … for alcohol intake of 22–27 drinks per week, compared to 1–3 drinks per week. Among alcohol consumers, weekly alcohol intake increased the risk of breast cancer with 2% for each additional drink consumed. Weekend consumption increased the risk with 4% for each additional drink consumed Friday through Sunday." Binge drinking of 4–5 drinks on the last weekday increased risk by 55%.[23]

"The findings from this prospective study suggest that moderate alcohol consumption increases breast cancer risk."[24]

A study showed that one or two alcoholic drinks a day increases the risk of breast cancer by 10 per cent compared with light drinkers who drank less than one drink a day. Women who have three or more drinks a day increase their risk of breast cancer by 30 per cent. The type of drink was not a factor.[25]

"Folate intake counteracts breast cancer risk associated with alcohol consumption"[26] and "women who drink alcohol and have a high folate intake are not at increased risk of cancer".[27] Those who have a high (200 micrograms or more per day) level of folate (folic acid or Vitamin B9) in their diet are not at increased risk of breast cancer compared to those who abstain from alcohol.[28] A study of over 17,000 Australian women aged 40-69 over a period of about ten years found that those who consumed 40 grams of alcohol (about three to four drinks) per day have a higher risk of breast cancer than do women who abstain from alcohol. However, in women who take 200 micrograms of folate or folic acid (Vitamin B9) every day, the risk of breast cancer drops below that of alcohol abstainers. (Baglietto, Laura, et al. Does dietary folate intake modify effect of alcohol consumption on breast cancer risk? Prospective cohort study. British Medical Journal, August 8, 2005) See Folic acid for more.

A study on mice suggests that, when breast cancer is established, drinking as little as two alcoholic drinks a day increases the growth rate of tumors. Alcohol causes cancer cells' blood vessels to grow which in turn fuels the growth of the tumor, a process known as angiogenesis.[29]

Colorectal cancer

Colorectal cancer refers to cancers of the colon or rectum. Colorectal cancer constitutes about 9.7% of all cancers.[9]The National Cancer Institute does not list alcohol as a risk factor.[30]

The NIAAA reports that, "Epidemiologic studies have found a small but consistent dose-dependent association between alcohol consumption and colorectal cancer[31][32]even when controlling for fiber and other dietary factors.[33][34] Despite the large number of studies, however, causality cannot be determined from the available data."[2]

"Heavy alcohol use may also increase the risk of colorectal cancer" (NCI). One study found that "People who drink more 30 grams of alcohol per day (and especially those who drink more than 45 grams per day) appear to have a slightly higher risk for colorectal cancer."[35][36] Another found that "The consumption of one or more alcoholic beverages a day at baseline was associated with approximately a 70% greater risk of colon cancer."[37][38][39]

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.".[40]

Other research suggests that "to minimize your risk of developing colorectal cancer, it's best to drink in moderation"[2]

The EPIC study suggests that "people who drink 15 grams of alcohol a day - equivalent to about two units - have about a 10 per cent 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." [41][42]

In “Moderate Alcohol Consumption Protects Against Colorectal Adenoma, ” Dr. Gregory Austin of the University of North Carolina at Chapel Hill and his colleagues found from an analysis of a case control study of patients who underwent a full colonoscopy that abstainers or non-drinkers had a 40% higher risk of adenoma than did those who consumed beer, wine, or liquor (distilled spirits) in moderation. The researchers conclude that “Individuals who consume moderate amounts of alcohol are at lower risk of colorectal adenomas than nondrinkers and heavy drinkers.” (Austin, Gregory, et al. Moderate Alcohol Consumption Protects Against Colorectal Adenoma. Paper presented at Digestive Diseases Week (DDW), May 24, 2006 , abstract M2263) [3]

Drinking may be a cause of earlier onset of colorectal cancer.[43]

Heavy alcohol drinking appears to be a risk factor for these cancers

Liver cancer

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."[44][45]

"The chances of getting liver cancer increase markedly with five or more drinks per day" (NCI). However, the risk is cut dramatically by consuming coffee daily.[46] Research has now demonstrated that drinking four cups of coffee per day reduces alcoholic cirrhosis risk by 80% among both men and women of different racial categories (Klatsky et al., Coffee, cirrhosis, and tranaminase enzymes. Archives of Internal Medicine, 2006, 166, 1190-1195).

In areas of Africa and Asia, liver cancer afflicts 50 or more people per 100,000 per year, usually associated with cirrhosis caused by hepatitis viruses. 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[1][47][2] "Mortality rates of hepatocellular carcinoma (HCC) are high in Italy compared with other Western countries. … Overall, 61% of HCC were attributable to HCV [hepatitis C virus], 13% to HBV [hepatitis B virus], and 18% to heavy alcohol drinking."[48] 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."[49]

Liver and intrahepatic bile duct cancers combined account for about 2.8% of all cancers.[9]

Ovarian cancer

"Associations were also found between alcohol consumption and cancers of the ovary …, but only for 50 g and 100 g a day."[50] "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."[51]

Breast cancer in men

"Heavy alcohol intake increases the risk of breast cancer in men."[52] "If you drink heavy amounts of alcohol, you have a greater risk of breast cancer."[53]

Male breast cancer is very rare and, in Western populations, the incidence is less than one case per 100,000 men. Male Breast Cancer

Evidence appears to be inconsistent regarding these cancers

Leukemia

Leukemia (British spelling: leukaemia). There is no association between drinking alcohol and adult leukemia.

“Results from the few studies that have examined the association between alcohol use during pregnancy and childhood leukemia are conflicting,” reported a study that found an association."[54] A review published by the National Cancer Institute placed maternal alcohol consumption during pregnancy in the category of “suggestive” and asserts that it is “unlikely to be an important risk factor.” [55]

Leukemia constitutes about 7.8% of all cancers.[9]

Malignant melanoma

"In interview data from the U.S.A.'s Third National Cancer Survey, alcohol ingestion was associated with a higher occurrence of cancers of the breast, thyroid, and malignant melanoma. Data from other studies support the first two associations."[56] "High alcohol consumption was associated with an increased risk for melanoma, which remained after adjustment for confounders…".[57] Other studies suggest there is no association for melanoma. "The risk of malignant melanoma was not influenced by alcohol consumption or smoking habits."[58] "There was no evidence that … alcohol or polyunsaturated fats were associated with an increased risk."[59]

There is no association between alcohol and Nonmelanoma skin cancer.

Prostate cancer

"Associations were also found between alcohol consumption and cancers of the ovary and prostate, but only for 50 g and 100 g a day."[50] However, one study concludes, "In contrast to the majority of previous studies, we found a positive association between moderate alcohol consumption and the risk of prostate cancer. Liquor, but not wine or beer, consumption was positively associated with prostate cancer."[60]

The Fred Hutchinson Cancer Research Center "found that men who consumed four or more glasses of red wine per week reduced their risk of prostate cancer by 50 percent". 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.".[61][62]

Prostate cancer accounts for about 4.8% of all cancers.[9]

Thyroid cancer

"In interview data from the U.S.A.'s Third National Cancer Survey, alcohol ingestion was associated with a higher occurrence of cancers of the breast, thyroid, and malignant melanoma. Data from other studies support the first two associations."[56] Another study suggests that drinking in moderation significantly reduces the risk of some malignant tumors such as thyroid cancer in women.[63] However, another study concludes, "A reduced risk associated with alcohol was eliminated after adjustment for smoking…".[64]

Alcohol appears to reduce risk of these cancers

Hodgkin's lymphoma (HL)

"Our study indicates a protective effect of alcohol consumption for nonsmoking HL cases."[65]

The National Cancer Institute does not list alcohol consumption as a risk factor for Hodgkin's lymphoma.[4]

Kidney cancer (Renal cell carcinoma) (RCC)

Moderate alcohol consumption appears to reduce the risk of kidney cancer. An analysis of data from 760,044 men and women who were tracked for seven to 20 years found that moderate drinkers are about 30% less likely to develop renal cell cancer than are abstainers. (Lee, J. E. et al. Alcohol intake and renal cell cancer in a pooled analysis of 12 prospective studies. Journal of the National Cancer Institute, 2007, 99, 811-822.)

A large prospective study of 59,237 Swedish women age 40-76 found that those who consumed at least one drink per week had a 38% lower risk of kidney cancer than did abstainers or those who drank less. For women over 55, the risk dropped by two-thirds (66%). [66]

A small study concluded that its "findings suggest an inverse association of alcohol consumption and RCC development among women but not among men."[67] Another small study concluded that "No significant relationship emerged, nor any differences between the sexes."[68]

Non-Hodgkin's lymphoma

A review of findings from nine international studies suggests that drinking alcohol reduces the risk of non-Hodgkin’s lymphoma (NHL) by 27%. The protective effect of alcohol did not vary by beverage type. "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. Further study designs are needed to determine whether confounding lifestyle factors or immunomodulatory effects of alcohol explain this association.".[69] The research also found that, in addition, alcohol's protective effect varies by form or subtype of non-Hodgkin‘s lymphoma. Drinkers were about half as likely as non-drinkers to develop Burkitt's lymphoma.

The cancer is the sixth most common in the USA.

Alcohol appears not to be a risk factor for these cancers

Bladder cancer

"Our data suggest that total and beverage-specific alcohol consumption are not associated with an increased risk of bladder cancer."[70] A Dutch study concludes, "The results of this study do not suggest an important association between alcohol consumption and bladder cancer risk."[71] Bladder cancer represents about 2.3% of all cancers.

Endometrial cancer

"Thirteen studies to date have reported on the relationship between endometrial cancer and alcohol consumption. Only two of these studies have reported that endometrial cancer incidence is associated with consumption of alcohol; all the others have reported either no definite association, or an inverse association." (Six studies showed an inverse association; that is, drinking was associated with a lower risk of endometrial cancer) "…if such an inverse association exists, it appears to be more pronounced in younger, or premenopausal, women."[72]

Endometrial plus all other uterine cancers account for about 1.9% of all cancers.[9]

Gallbladder cancer

The National Cancer Institute does not list alcohol as a risk factor for gallbladder cancer (National Cancer Institute. General Information about Gallbladder Cancer).

A letter to the editor of the International Journal of Cancer [5] suggested that “incidence differences for gallbladder cancer between occupational groups suggest an etiological role for alcohol.” The investigators did not use any direct measure of alcohol consumption and their surrogate indicator was confounded by smoking. They reported that “Occupations with high consumption of alcohol and/or high prevalence of smoking associated with a risk of liver and gallbladder cancers” which led to their conclusion that “alcohol drinking is a risk factor of gallbladder cancer because of the covariation of primary liver and gallbladder cancers in occupational groups.” (Ji, J; Hemminki K (2005 Sep). "Variation in the risk for liver and gallbladder cancers in socioeconomic and occupational groups in Sweden with etiological implications". Int Arch Occup Environ Health 78 (8): 641-9) However covariation alone cannot establish that any variable is a risk factor.

Researchers using direct measures of drinking have not found alcohol to be a risk factor for the disease. A French study of female gallbladder patients found that only 2% consumed alcohol [6] and a Polish case-controlled study found no relationship between alcohol consumption and the disease .[7]

A large multicultural case-control study of gallbladder cancer was conducted in Australia, Canada, the Netherlands and Poland with the Surveillance of environmental Aspects Related to Cancer in Humans (SEARCH) Program of the International Agency for Research on Cancer (IARC). It found no evidence that alcohol is a risk factor for gallbladder cancer. [8]

Lung cancer

"Globally, lung cancer is the most frequent malignancy in males, while it is the fifth most common cancer in females." [9] It is a major cause of death, constituting about 28.8% of all cancers.[9] The NIAA reports that “A few studies have linked chronic heavy drinking with cancers of the stomach, pancreas, and lungs (International Agency for Research on cancer). However, the association is consistently weak and the majority of studies have found no association (International Agency for Research on Cancer).”[2]

Chronic heavy alcohol consumption possibly increases the risk of lung cancer, but the evidence is inadequate to date.[73] Commenting on a study by Freudenheim et al[74] 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."[75]

Pancreatic cancer

"A few studies have linked chronic heavy drinking with cancers of the stomach, pancreas, and lungs. However, the association is consistently weak and the majority of studies have found no association", write the NIAAA,[2] citing the International Agency for Research on Cancer..[76] Alcohol has been reported as a possible risks in some (but not in most) studies.[77] Drinking alcohol excessively is a cause of acute pancreatitis and chronic pancreatitis. "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."[78]

Pancreatic cancer constitutes about 5.7% of all cancers.

Small intestine cancer

The National Cancer Institute does not list alcohol as a possible risk factor for cancer of the small intestine. [10]

Stomach cancer

As indicated above, the NIAA reports that “A few studies have linked chronic heavy drinking with cancers of the stomach, pancreas, and lungs (International Agency for Research on cancer). However, the association is consistently weak and the majority of studies have found no association (International Agency for Research on Cancer).”[2]

Alcohol consumption, even when chronic and heavy, probably does not affect the risk of stomach cancer.[73]

Vulvar cancer

The American Caner Society does not list alcohol as a risk factor for this disease [11] "No consistent association emerged between milk, meat, liver, alcohol and coffee consumption and risk of vulvar cancer."[79]

Thirty other cancers

Alcohol is not listed as a risk factor for any of the following cancers

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). "In conclusion we found that alcohol intake was closely related to the tumor growth of HCC in patients with type C cirrhosis."[81]

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.[82][83] A 2006 study in mice showed moderate drinking resulted in larger and more robust tumors.[84]

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 - particularly that of 'killer t-cells'.[85][86]

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 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)"[87][88]

Alternatively, the actual quantities of alcohol associated with negative effects may be substantially higher than generally reported because participants in medical research studies tend to underestimate and underreport their usual amounts of alcohol consumption.[89]

Relative health risks

An increase in risk of a particular cancer through drinking needs to balanced against the benefits of moderate drinking on reducing heart attacks. See Alcohol and heart attacks for more. There are, of course, many ways of reducing your risk of a heart attack either without, or in addition to, drinking alcohol, such as controlling your weight and exercising. Balancing such risks is a personal decision that should be discussed with one’s own physician.

See also

References

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