Alcohol ‘flush’ signals cancer risk in Asians

Medical Tribune June 2009 P4

David Brill

East Asians who ‘flush’ when drinking alcohol could be at increased risk of esophageal cancer if they do not drink responsibly, a recent study has warned.

The characteristic red cheeks and nausea are a well-recognized phenomenon, but few people are aware that the underlying enzyme deficiency also predisposes heavy drinkers to squamous cell esophageal carcinoma, say the researchers.

With some 36 percent of East Asians displaying the flush response, there is potential to save “a substantial number of lives” by counseling affected individuals against heavy drinking. [PLoS Med 2009 Mar 24;6(3):e50]

"Cancer of the esophagus is particularly deadly, with 5-year survival rates ranging from 12 to 31 percent throughout the world,” said lead researcher Dr. Philip Brooks, of the US National Institute on Alcohol Abuse and Alcoholism. “And we estimate that at least 540 million people have this alcohol-related increased risk for esophageal cancer.

"We hope that by raising awareness of this important public health problem, affected individuals who drink will reduce their cancer risk by limiting their alcohol consumption," he said.

Flushing is caused by a deficiency in aldehyde dehydrogenase 2 (ALDH2) – an enzyme which breaks down acetaldehyde, a carcinogenic by-product of ethanol metabolism. People with normal ALDH2 function can convert acetaldehyde safely into acetate, but in ALDH2-deficient individuals it accumulates in the body, leading to facial redness, nausea and tachycardia.

In people who are homozygous for the ALDH2-deficiency gene, the response to alcohol is so unpleasant that they cannot consume large quantities, and are thereby protected from the associated risk of esophageal cancer.

Heterozygotes, however, can develop tolerance to acetaldehyde and may become heavy drinkers. Studies from Japan and Taiwan have shown that ALDH2-deficient heterozygotes who drink heavily are over ten times as likely to develop esophageal cancer, [Jpn J Clin Oncol 2003 Mar;33(3):111-21; Int J Cancer 2008 Mar 15;122(6):1347-56]

Dr. Michael Wang, a radiation oncology consultant at the National Cancer Centre Singapore, agreed that the link between flushing and esophageal cancer is not likely to be common knowledge among doctors.

“From the article, it is fair to comment that there is a causative relation between deficiency of the gene and increased risk of esophageal cancer,” he said.

“However, there has been a lot of material published since the 1970s regarding this condition. This relationship may be confounded by smoking, which is also related to esophageal cancer. Before we say something drastic like ‘people who flush when drinking have a higher risk of contracting esophageal cancer,’ we should research all the previously published articles first.”
Wang added that all heavy alcohol drinkers should be counseled, since drinking also predisposes to other medical conditions and to drink-driving.

The study authors advise clinicians to determine whether East Asian patients are ALDH2 deficient by asking simple questions about their history of flushing when drinking alcohol. Identified flushers should then be advised of their cancer risk and encouraged to moderate their consumption, they say.