The Nuts and Bolts of Increased Risk
The biological mechanisms that mediate alcohol-related cancer are not fully understood. Alcoholic beverages can contain at least 15 carcinogenic compounds, including acetaldehyde, acrylamide, aflatoxins, arsenic, benzene, cadmium, ethanol, ethyl carbamate, formaldehyde, and lead. Ethanol is the most important carcinogen in alcoholic beverages, and the rate of ethanol metabolism is genetically determined.
The first and most toxic product of alcohol metabolism is acetaldehyde. Ingested ethanol is oxidized by the enzymes alcohol dehydrogenase, cytochrome P4502E1, and catalase to form acetaldehyde. Acetaldehyde also occurs naturally in alcoholic beverages. This metabolite is carcinogenic and genotoxic when in contact with the mucosa of the upper aerodigestive tract (pharynx, oral cavity, esophagus, larynx), where high concentrations of acetaldehyde induce mucosal hyperproliferation. Even low doses of alcohol in direct contact with these areas can increase the risk for cancer.
Several different causative pathways are implicated in alcohol-related cancer. For example, alcohol is a folate antagonist, and an alteration in folate metabolism and folate malabsorption are believed to interact with ethanol to impair DNA methylation. In breast cancer, alcohol can increase estrogen levels and the activity of insulin-like growth factor receptors, which can stimulate mammary cell proliferation. In digestive tract cancers, an individual's genotype could play a role. Other mechanisms that have been proposed include the production of reactive oxygen and nitrogen species, and a role for alcohol as a solvent of tobacco carcinogens.
The Hard Truth About Hard Liquor
The relative risk for alcohol-associated cancer depends on where ingested alcohol contacts body tissue, according to Dr. Rehm. Alcohol first contacts the oral cavity, followed by the esophagus, and for these sites the relative risk for alcohol-related cancer is highest. Next are the colon, rectum, and liver, and the relative risks for those cancers are lower than for the anatomical sites first in contact with ingested alcohol.
The type of alcohol -- wine, beer, spirits -- doesn't usually matter, except in the case of cancer of the esophagus. The esophagus is covered with very fine cilia that are easily destroyed by high concentrations of ethanol, such as found in hard liquor.
A Drink and a Smoke: Dangerous Combination
Smoking has long been established as a risk factor for cancer. But smoking and drinking -- considered by many to be a pleasurable combination -- is a particularly dangerous mix. A synergistic effect has been found for tobacco smoking and alcohol consumption with respect to the risk for cancers of the oral cavity, pharynx, larynx, and esophagus; the highest risks are seen in those who are both heavy drinkers and heavy smokers. The esophageal mucosa of patients who both drink and smoke have shown a dose-dependent increase in esophageal mucosal cell proliferation. Avoidance of cigarettes and alcohol could prevent up to 80% of oral cancer cases and 90% of laryngeal cancer cases.
Medscape Oncology © 2014
Cite this: No Amount of Alcohol Is Safe - Medscape - Apr 30, 2014.