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Drinkers with the Alcohol Dehydrogenase 1C*1 Gene are at Greater Risk of Colorectal Cancer

March 1, 2009

Nils Homann, Inke R. König, Michael Marks, Monika Benesova, Felix Stickel, Gunda Millonig, Sebastian Mueller, and Helmut K. Seitz. (March 2009). Alcohol and colorectal cancer: the role of alcohol dehydrogenase 1C polymorphism. Alcoholism: Clinical & Experimental Research (ACER). 33(3): 551-556.

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These individuals create more carcinogenic acetaldehyde, which causes greater cellular DNA damage

  • Chronic drinking is a known risk factor for colorectal cancer, possibly due to the creation of acetaldehyde by the alcohol dehydrogenase (ADH) enzyme.
  • New findings show that individuals with a polymorphism of the ADH1C gene produce more acetaldehyde when they drink, which creates a higher risk for colorectal cancer.

Chronic drinking is a risk factor for colorectal cancer, possibly through the effects of acetaldehyde, which is created by the alcohol dehydrogenase (ADH) enzyme. This study investigated if a polymorphism of the ADH1C gene that is found in Caucasians may effect acetaldehyde concentrations. Findings confirm ADH1C*1 as a genetic risk marker for colorectal tumors among people who drink more than 30 grams of alcohol per day.

Results will be published in the March issue of Alcoholism: Clinical & Experimental Research and are currently available at Early View.

“In 2007, the International Agency for Research on Cancer clearly stated that chronic alcohol consumption increases the risk for colorectal cancer,” said Helmut K. Seitz, professor of internal medicine, gastroenterology and alcohol research at the University of Heidelberg. “This has enormous practical implications since, in many countries, alcohol consumption is high and the prevalence of colorectal cancer is increasing. In other words, one of the leading types of cancers worldwide is further stimulated by alcohol drinking.” Seitz is also the study’s corresponding author.

“Regular alcohol consumption of about 50 grams or approximately four drinks per day results in a 1.4-fold risk for colorectal cancer compared to non-drinkers,” added Mikko Salaspuro, professor at the University of Helsinki, and a specialist in internal medicine and in gastroenterology at the Helsinki University Central Hospital.

Acetaldehyde is the first metabolite of alcohol, both researchers explained. The more acetaldehyde produced, the higher the risk of cellular DNA damage, leading to cancer. While studies of upper digestive tract cancers have strongly implicated exposure to acetaldehyde in saliva, both direct and indirect evidence also implicate the role of acetaldehyde in the cells of the colonic mucosa and cancer development in the colorectum.

For this study, Seitz and his colleagues recruited 173 individuals (138 males, 35 females) with colorectal tumors diagnosed by total colonoscopies, and 788 “control” patients (523 males, 265 females) without colorectal tumors. Whole-blood genotyping was performed on all participants.

“Our results show that individuals who metabolize alcohol to acetaldehyde more rapidly produce more acetaldehyde, and therefore have an increased risk for cancer in the colorectum,” said Seitz. “This metabolism is modulated by the activity of an important enzyme called alcohol dehydrogenase, which is genetically controlled. Thus, acetaldehyde plays a major role in alcohol-mediated carcinogenesis, and may not only be a carcinogen for the large intestine, but also for the upper aero digestive tract and the breast, as shown by other studies.”

Both Seitz and Salaspuro said these findings provide a cautionary tale for certain individuals “Those with other risks for colorectal cancer may want to limit their alcohol intake to less than 30 grams per day, and possibly occasional instead of regular alcohol intake,” said Seitz.

“Whether or not they are at higher risk for colorectal cancer,” added Salaspuro, “all can decrease their risk if they dont drink, or drink in moderation.”