Alcohol drinking increases the risk for a number of
cancers. Currently, the highest risk (Group 1) concerns oral cavity, pharynx, larynx, esophagus, liver, colorectum, and female breast, as assessed by the International Agency for Research on
Cancer (IARC). Alcohol and other beverage constituents, their metabolic effects, and alcohol-related unhealthy lifestyles have been suggested as etiological factors. The aim of the present survey is to evaluate the carcinogenic role of
acetaldehyde in alcohol-related
cancers, with special emphasis on the genetic-epidemiological evidence.
Acetaldehyde, as a constituent of alcoholic beverages, and microbial and endogenous alcohol oxidation well explain why alcohol-related
cancers primarily occur in the digestive tracts and other tissues with active alcohol and
acetaldehyde metabolism. Genetic-epidemiological research has brought compelling evidence for the causality of
acetaldehyde in alcohol-related
cancers. Thus, IARC recently categorized alcohol-drinking-related
acetaldehyde to Group 1 for head and neck and
esophageal cancers. This is probably just the tip of the iceberg, since more recent epidemiological studies have also shown significant positive associations between the
aldehyde dehydrogenase ALDH2 (rs671)*2 allele (encoding inactive
enzyme causing high
acetaldehyde elevations) and gastric, colorectal, lung, and
hepatocellular cancers. However, a number of the current studies lack the appropriate matching or stratification of alcohol drinking in the case-control comparisons, which has led to erroneous interpretations of the data. Future studies should consider these aspects more thoroughly. The polymorphism phenotypes (
flushing and
nausea) may provide valuable tools for future successful health education in the prevention of alcohol-drinking-related
cancers.