Elsevier

The Lancet Oncology

Volume 7, Issue 2, February 2006, Pages 149-156
The Lancet Oncology

Review
Alcohol and cancer

https://doi.org/10.1016/S1470-2045(06)70577-0Get rights and content

Summary

A causal association has been established between alcohol consumption and cancers of the oral cavity, pharynx, larynx, oesophagus, liver, colon, rectum, and, in women, breast; an association is suspected for cancers of the pancreas and lung. Evidence suggests that the effect of alcohol is modulated by polymorphisms in genes encoding enzymes for ethanol metabolism (eg, alcohol dehydrogenases, aldehyde dehydrogenases, and cytochrome P450 2E1), folate metabolism, and DNA repair. The mechanisms by which alcohol consumption exerts its carcinogenic effect have not been defined fully, although plausible events include: a genotoxic effect of acetaldehyde, the main metabolite of ethanol; increased oestrogen concentration, which is important for breast carcinogenesis; a role as solvent for tobacco carcinogens; production of reactive oxygen species and nitrogen species; and changes in folate metabolism. Alcohol consumption is increasing in many countries and is an important cause of cancer worldwide.

Introduction

A causal link has been established between alcohol consumption and cancers of the oral cavity, pharynx, oesophagus, liver, colon, rectum, and, in women, breast (figure).1 For other cancers, a causal association is suspected. The importance of alcohol as a human carcinogen is often underestimated: consumption is rising in many countries as a result of both increasing numbers of alcohol drinkers and intake of alcohol, especially for women and in regions of rapid economic growth such as east Asia.2 Alcohol is probably the main factor responsible for increased risk of head and neck cancer recorded in various countries, particularly in central and eastern Europe.3 Evidence suggests that genetic susceptibility plays an important part in alcohol-related cancer, and knowledge of possible mechanisms of the carcinogenic action of alcohol has increased in recent years.

Here, we review the carcinogenic effects of alcohol consumption in human beings. Alcohol modifies the risk of several diseases other than cancer, but a detailed review of these effects is beyond the scope of this review. Briefly, the major non-neoplastic diseases caused by alcohol are: alcoholic polyneuropathy; alcoholic cardiomyopathy; alcoholic gastritis; depression and other mental disorders;4, 5 hypertension;6 haemorrhagic stroke;7 liver cirrhosis and fibrosis;8 and acute and chronic pancreatitis.9 Moreover, alcohol consumption is a major cause of several types of injuries,5 and the drinking of alcohol during pregnancy is associated with various adverse effects including fetal alcohol syndrome, spontaneous abortion, low birthweight, premature birth, and intrauterine growth retardation.10

However, evidence suggests that moderate consumption (up to two drinks per day) of alcohol reduces the risk of ischaemic heart disease,11 ischaemic stroke,7 and colelithiasis.5 A global assessment of the burden of alcohol consumption on human health is complicated by several factors, including: background frequency of major diseases such as ischaemic heart disease and liver cirrhosis; age distribution of a population, since incidence of many alcohol-related injuries decreases with age whereas that of cancer and ischaemic heart disease increases with age; and pattern of consumption, since the protective effect on ischaemic heart disease is not present at high intake.

The most comprehensive estimate of the number of deaths caused and prevented by alcohol has been done as part of WHO's global burden of disease project.5 According to this assessment, alcohol caused 185 000 deaths of men in developed countries in 2000, whereas it prevented 71 000 deaths in men for the same year. For women in developed countries, 277 000 deaths were prevented compared with the 142 000 caused by alcohol. However, in developing countries, a lower burden of cardiovascular disease and a greater incidence of injuries compared with developed countries led to 1 524 000 deaths in men and 301 000 in women in 2000. Therefore, the global burden of alcohol amounts to 1 804 000 deaths a year, or 3·2 % of all deaths a year.

Section snippets

Epidemiology of alcohol-related cancer

From the articles identified by our search, we focused on those that reported risk estimates for alcohol consumption, particularly ones that assessed: dose-response relations; differences by type of alcoholic beverage; and interactions with other risk factors for a particular cancer. When meta-analyses were available for a particular cancer, we reported the most recently published summary estimate.

Genetic susceptibility to alcohol-related cancer

Evidence suggests that the risk of cancer for alcohol drinkers is modulated by genetic factors. Research has focused on variants in genes for alcohol metabolism, folate metabolism, and DNA repair.

Mechanisms of alcohol carcinogenicity

The mechanisms by which alcoholic drinks exert their carcinogenic effect are not understood fully and probably differ by target organ, as do other carcinogens that act at many sites. Table 2 lists known or suspected mechanisms of carcinogenicity of alcoholic drinks, together with our subjective assessment of the strength of the available evidence.

Pure ethanol does not act as a carcinogen in animal studies,1, 2 and thus alcoholic drinks might act as a solvent for penetration of carcinogens

Conclusion

Alcohol consumption is one of the most important known causes of human cancer after tobacco smoking, chronic infections, and possibly obesity. With the exception of aflatoxin, for no dietary factor is there such strong and consistent evidence for carcinogenicity. In central and eastern Europe, the burden of alcohol-associated cancer, and of other alcohol-associated disease, is substantial. Alcohol consumption is increasing rapidly in many parts of the world, such as east Asia.2 For breast

Search strategy and selection criteria

We searched Medline using the keywords “alcohol drinking”, “neoplasms”, and “risk factor” from 1966 to 2005. There were no language restrictions.

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