March 31st, 2009

Alcohol-induced Flushing Linked with Esophageal Cancer


People who experience facial flushing after consuming alcohol may have an increased risk of developing alcohol-related esophageal cancer. These results were published in PLoS Medicine.

Worldwide, an estimated 3.5% of all cancer deaths are attributable to alcohol.[1] Links have been established between alcohol and several types of cancer, including cancers of the mouth, pharynx, larynx, esophagus, breast, colon and rectum, and liver.[2] Risk of some of these cancers—such as cancer of the mouth— is particularly elevated in people who both smoke and drink.

The way in which alcohol contributes to cancer development is still uncertain, and may vary by cancer type, but there are several possible explanations for the link. In the case of breast cancer, many researchers have speculated that alcohol increases risk by altering the levels of hormones such as estrogen.[3] The risk of breast and other cancers may also be increased by potentially carcinogenic compounds such as acetaldehyde that are produced during alcohol metabolism (the processing of alcohol by the body). The extent to which drinkers are exposed to acetaldehyde may be influenced by inherited differences in genes involved in alcohol metabolism, and researchers are evaluating whether these genetic differences influence the risk of cancer in drinkers.[4]

One gene that may be important is ALDH2. The links among ALDH2 variants, flushing after drinking, and alcohol-related esophageal cancer were discussed in an article recently published in the journal PLoS Medicine.[5] 

The ALDH2 gene usually produces an enzyme that converts acetaldehyde to another compound. Some people, however, have a variant of the gene that produces an inactive or less active version of the enzyme. This increases exposure to acetaldehyde after drinking. The gene variants linked with reduced or absent ALDH2 enzyme activity are particularly common among East Asians (Japanese, Chinese, and Koreans).

People with inactive versions of the ALDH2 enzyme tend to avoid alcohol as a result of an intensely unpleasant response that may include flushing, nausea, and tachycardia (rapid heart rate). Flushing also occurs in people with reduced enzyme activity, but the response tends to be less severe and some people are able to develop a tolerance for alcohol. It is these people (those with reduced but not completely eliminated ALDH2 activity) who appear be the most likely to develop alcohol-related esophageal cancer. Importantly, risk of esophageal cancer is not increased among nondrinkers with reduced ALDH2 levels.

In summary, people who experience facial flushing after drinking may have an ALDH2 deficiency and an increased risk of alcohol-related esophageal cancer. The researchers note that “Doctors should counsel their ALDH2-deficient patients to limit alcohol consumption and thereby reduce the risk of developing esophageal cancer.”


[1] Boffetta P, Hashibe M, La Vecchia C, Zatonski W, Rehm J. The burden of cancer attributable to alcohol drinking. International Journal of Cancer. 2006;119:884-887.

[2] World Cancer Research Fund / American Institute for Cancer Research. Food, Nutrition, Physical Activity, and the Prevention of Cancer: a Global Perspective. Washington DC: AICR, 2007.

[3] Rinaldi S, Peeters PHM, Bezemer ID et al. Relationship of alcohol intake and sex steroid concentrations in blood in pre- and post-menopausal women: the European Prospective Investigation into Cancer and Nutrition. Cancer Causes and Control. 2006;17:1033-1043.

[4] Terry MB, Gammon MD, Zhang FF et al. ADH3 genotype, alcohol intake and breast cancer risk. Carcinogenesis. 2006;27:840-847.

[5] Brooks PJ, Enoch M-A, Goldman D, Li T-K, Yokoyama A. The alcohol flushing response: an unrecognized risk factor for esophageal cancer from alcohol consumption. PLoS Medicine. March 2009;6(3):e1000050.

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Tags: Esophageal Cancer, Uncategorized