Acetaldehyde: Why Ethanol's First Metabolite Is the Carcinogenic One

Acetaldehyde is the first product of ethanol metabolism and the compound most directly implicated in alcohol-related cancer. The International Agency for Research on Cancer classified acetaldehyde associated with alcohol consumption as carcinogenic to humans in 2009, the year after classifying alcoholic beverages themselves as a Group 1 carcinogen. **Where it comes from.** When ethanol is consumed, it is oxidized to acetaldehyde by alcohol dehydrogenase, cytochrome P450 2E1, and bacterial catalases — including bacteria living in the mouth and gut. Normally the enzyme ALDH2 (aldehyde dehydrogenase 2) rapidly converts about 99% of acetaldehyde into harmless acetate for excretion. **Why it causes cancer.** Acetaldehyde is genotoxic: it can bind DNA to distort its shape and to block repair and synthesis machinery, inducing mutations, strand breaks and chromosomal exchanges. In tissues that ethanol contacts directly — the mouth, pharynx and esophagus — a local mechanism operates: ethanol kills surface cells, stem cells divide to replace them, and those dividing cells are exposed to acetaldehyde's DNA damage. This is why alcohol is a risk factor for head-and-neck cancers at any quantity, and why combined drinking and smoking multiplies the risk dramatically. **Genetic variation.** People carrying the ALDH2*2 allele — present in roughly 28-45% of East Asian populations — convert acetaldehyde to acetate more slowly. The resulting buildup causes facial flushing after small amounts of alcohol and, importantly, raises their risk of these cancers because the carcinogen lingers longer. Acetaldehyde is the central reason concerns are raised about ethanol delivered directly to the oral cavity, including by alcohol-containing mouthwash, though the mouthwash-specific epidemiology remains unsettled.