Genetic Polymorphisms and Alcohol-Related Cancers
Alcohol, responsible for 4% of cancer deaths worldwide, is metabolized by alcohol dehydrogenases (ADHs) to acetaldehyde, which is then converted to acetate by aldehyde dehydrogenase (ALDH). Acetaldehyde is carcinogenic in animals. French investigators systematically searched Medline to find studies of the effects of alcohol and ADH and ALDH polymorphisms on cancer risk. The most consistent findings were for ADH1B and ALDH2 polymorphisms that code for less active forms of the enzymes.
- In both Asian and European populations, the ADH1B*1 allele was associated with greater risks for head and neck, pharyngeal, and esophageal cancers among moderate and heavy drinkers. In 1 study, moderate drinkers with the allele had 26 times the risk of esophageal cancer compared with nondrinkers with the ADH1B*2/ADH1B*2 genotype.
- Among Asians, moderate and heavy drinkers with the ALDH2*2 allele were at higher risk for oropharyngeal and esophageal cancers than nondrinkers without the allele.
- Europeans with ALDH2 variants who drank moderate or heavy amounts were also at higher risk for upper aerodigestive tract cancers.
Comments:In the case of ALDH, the association with alcohol-related cancer seems to make sense: the risky allele allows a carcinogen to accumulate. For ADH, the risky allele (predominant in most populations) codes for a less active enzyme, leading to less acetaldehyde production. The authors speculate that such people do not flush when they drink and, therefore, might drink more frequently and heavily, increasing their vulnerability. This review included only retrospective case-control studies; prospective studies are needed to better understand the undoubtedly complex associations between alcohol and cancers. Richard Saitz, MD, MPH
Druesne-Pecollo N, Tehard B, Mallet Y, et al. Alcohol and genetic polymorphisms: effect on risk of alcohol-related cancer. Lancet Oncol. 2009;10(2):173–180.