Rs671 allele (A), also known as ALDH*2 variant, in the aldehyde dehydrogenase gene (ALDH2) encodes for a form of aldehyde dehydrogenase 2 protein which is defective in metabolizing alcohol.

The body normally converts acetaldehyde into a harmless substance called acetate. But many people with East Asian descent have a mutation in the gene for aldehyde dehydrogenase (ALDH2) that prevents this reaction, leading to an accumulation of acetaldehyde and the "Asian flush" often seen in this population. The mutation, called ALDH2*2, has not been found in people of European or African descent.

Meanwhile, increased acetaldehyde caused by ALDH2*2 mutation doubles the chances of esophageal cancer. Alcohol and cigarette smoke also raise the odds of disease in almost double. But when a person with ALDH2*2 variant drinks and/or smoke, then, these risk factors work together producing a synergistic effect which dramatically increase the risk. The magnitude of the combined effect varies from study to study, but the general conclusion is that these three risk factors synergistically increase the risk of esophageal cancer.

In one of the largest studies to date (Cui et al., 2009), researchers found that in people with the ALDH2*2 variant who smoke, the odds of esophageal cancer were between 5.65 and 23.08 times higher than people without the mutation who did not smoke or drink. The wide range of risk has to do with the presence or absence of other common genetic risk factor in Asians is not included in this report.

The odds of esophageal cancer for drinkers with ALDH2*2 variant ranged from 6.98 to 55.65 times higher than those without the mutation who do not smoke or drink. When the three risk factors were present in a ALDH2*2 person, the chances of esophageal cancer increased from 23.74 to 189.26 times compared to people without the mutation and who abstain from drinking alcohol and smoking tobacco.

Having two copies of the ALDH2*2 means that a person cannot break down acetaldehyde. Even a small amount of alcohol leads to an accumulation of this toxin producing extremely unpleasant side effects of the alcohol detoxification reaction, resulting in most of these people dislike alcohol and not smoking at all costs. For this reason, data on the risks of esophageal cancer in this group in the context of alcohol consumption are scarce. It is assumed that the odds of esophageal cancer in people with two copies of the ALDH2*2 variation are much greater if they drink alcohol. People with a single copy of the ALDH2*2 drink alcohol as well, but their bodies are able to process some of acetaldehyde and their reactions are less severe. Some of these individuals develop tolerance to acetaldehyde, allowing them to drink large alcohol quantities and thus increasing the risk of esophageal cancer.

In the treatment of alcoholics often a drug called disulfiram (Antabus®) is used. Disulfiram works by blocking the enzyme aldehyde dehydrogenase and causing accumulation of acetaldehyde, mimicking the effects of ALDH2*2. Like those individuals with two copies of this mutation, people taking Antabus® have unpleasant effects after drinking even small amounts of alcohol.

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