In the June issue of Alcoholism: Clinical & Experimental Research, researchers explore a potential association between high rates of alcohol use and high rates of upper digestive cancers. They used a unique group to investigate their hypothesis: individuals who lack the aldehyde dehydrogenase-2 (ALDH2) gene.
Alcohol is metabolized principally in the liver by two enzymes that act sequentially. Alcohol dehydrogenase (ADH) converts alcohol to acetaldehyde; aldehyde dehydrogenase (ALDH) converts acetaldehyde to acetate. Acetate is then metabolized by tissues outside of the liver. As much as 50 percent of Chinese and Japanese lack the aldehyde dehydrogenase-2 (ALDH2) isoenzyme, a deficiency which allows acetaldehyde to accumulate in the blood and tissues after drinking. These individuals experience an unpleasant response to drinking alcohol, such as facial flushing, headaches, palpitations, dizziness and nausea. They also seem to have significantly higher rates of digestive tract cancers.
"We need to remember that ALDH2-deficient individuals number in the hundreds of millions," said Mikko Salaspuro, chairman of Alcohol Diseases at the University of Helsinki, a specialist in internal medicine and in gastroenterology at the Helsinki University Central Hospital, and lead author of the study. "Accordingly, ALDH2 deficiency is quantitatively the most important gene mutation potentially exposing humans to an increased risk of cancer." Salaspuro explained that high rates of digestive tract cancers among this population may be associated with high levels of salivary acetaldehyde, an association that provides "strong evidence" that salivary acetaldehyde is carcinogenic in humans.
Parotid glands are the main saliva-producing organs. Located next to each ear, they are connected by a duct to the upper gingival area under the upper lip. Most people produce approximately 1.5 liters of saliva per day. Usually taken for granted until it’s compromised, saliva is a clear, alkaline, semi-viscous liquid which helps both in the digestion of food as well as cleaning, helping to keep exfoliated epithelial cells, most bacteria, and food particles away from the teeth. Salaspuro’s study proposes that the parotid glands are able to metabolize alcohol into acetaldehyde.
Oral microflora may also produce acetaldehyde. Every individual has about 300 hundred different bacterial species in their mouth. That number increases exponentially in saliva, even more on tooth surfaces, and even more on gingival scrapings. Everyone develops their oral microflora within a few weeks after birth; many live and grow in people’s mouths on a platonic basis, but some are harmful, such as those producing tooth cavities or those producing acetaldehyde.
The study found that ALDH2-deficient Asians were exposed to two to three times higher salivary acetaldehyde levels than either Caucasians or Asians with normal ALDH every time they drank, and for as long as they had elevated blood alcohol levels. The ALDH2-deficiency seemed to prevent those subjects from eliminating salivary acetaldehyde. Those with the normal ALDH enzyme were able to remove the acetaldehyde, likely formed in the parotid gland, before it was secreted to their saliva. Which is not to say that normal ALDH levels completely protect heavy drinkers from salivary acetaldehyde; Salaspuro noted that Caucasians that drank heavily for a number of years had much higher rates (20 fold) of esophageal cancer.
"At higher salivary ethanol concentrations," he said, "even the individuals with normal ALDH can achieve carcinogenic acetaldehyde levels in the saliva."
Salaspuro said his study’s findings are important on several different levels. "We all produce potentially carcinogenic acetaldehyde in our saliva when we drink. The higher the acetaldehyde levels in the saliva, the higher the risk of digestive tract cancer. A person’s risk is enhanced if, one, they drink a lot; two, if they are ALDH2-deficient; three, if they smoke or have bad oral hygiene, both of which increase the potential to produce acetaldehyde from alcohol; and four, if they have individual oral microflora characteristics that place them at higher risk."
Ting-Kai Li, Distinguished Professor at the Indiana University School of Medicine agrees. "There’s a high degree of suspicion or probability that acetaldehyde, which comes from alcohol, is carcinogenic, and this may be a mechanism in the higher rates of cancer among ALDH2-deficient heavy drinkers. It’s not a one-to-one relationship, but it may increase the risk."
Salaspuro noted that before dietary means and cholesterol-lowering drugs were discovered, individuals with an inherited inability to remove normal blood cholesterol in their livers often died before they reached 30 years of age. He added: "Our findings open a new area, both for screening and preventive research, with respect to gastrointestinal tract cancer. I hope we will be able to one day use our findings about microbially produced acetaldehyde for the prevention of some types of cancers."
Funding for this Addiction Science Made Easy project is provided by the Addiction Technology Transfer Center National Office, under the cooperative agreement from the Center for Substance Abuse Treatment of SAMHSA.
Articles were written based on the following published research:
Väkeväinen, S., Tillonen, J., Agarwal, D. P., Srivastava, N., & Salaspuro, M. (2000, June). High salivary acetaldehyde after a moderate dose of alcohol in ALDH2-deficient subjects: Strong evidence of the local carcinogenic action of acetaldehyde. Alcoholism: Clinical and Experimental Research, 24(6), 873-877.
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