UB Study Reports Possible Link Between Alcohol-Metabolizing Enzyme, Breast Cancer

EDMONTON -- University at Buffalo researchers are the first to find an indication that premenopausal women with a fast-acting form of an alcohol-metabolizing enzyme who have at least two drinks a day have three times the risk of developing breast cancer compared to lighter drinkers with the fast-acting form, or those with the slow-acting form.

There was no relationship found for postmenopausal women, however.

Jo L. Freudenheim, Ph.D., UB associate professor of social and preventive medicine, presented the study findings today (Friday, June 13) at the annual meeting of the Society for Epidemiological Research.

"There is accumulating but not consistent evidence of a relationship between alcohol and breast cancer, especially in premenopausal women," Freudenheim said. "We know there are differences among people in the way they metabolize alcohol, and decided to investigate whether these differences could account for some of the inconsistencies."

The researchers concentrated on the enzyme alcohol dehydrogenase3, which exists in two forms, or polymorphisms -- a slow-acting form and a fast-acting form that doubles the rate at which alcohol is metabolized.

"No one else has looked at alcohol dehydrogenase and breast cancer," Freudenheim said," but researchers have looked at this enzyme and oral cancer and found a similar relationship."

Freudenheim and colleagues analyzed blood samples from 134 premenopausal and 181 post menopausal women with breast cancer and a similar number of women without breast cancer to determined enzyme type. All the women were white. Alcohol consumption two years, 10 years and 20 years ago was obtained by personal interview.

Results showed that premenopausal women who were heavier drinkers -- defined in this study as having at least two drinks a day -- and had the fast-acting form of the enzyme had a significantly higher risk of developing breast cancer than light drinkers.

There was no effect among postmenopausal women and there was no association between the fast-acting polymorphism itself and breast-cancer risk.

Freudenheim said that if the relationship between alcohol dehydrogenase, alcohol and breast cancer holds up in further studies and in other population groups, it may be because alcohol is metabolized to a substance called acetaldehyde, thought to be carcinogenic. The fast-acting enzyme type may produce acetaldehyde faster than the body can eliminate it, causing a build-up of the potential carcinogen, she suggested.

"If this finding is consistent, we may conclude it is acetaldehyde and not alcohol per se that is related to risk," Freudenheim said. "It is important in terms of research for what it tells us about the mechanism of how alcohol may contribute to causing breast cancer. In terms of the public health, the message should still be Œif a woman is concerned about breast cancer, she should drink moderately, if at all'."

Also participating in the research were Christine B. Ambrosone, Ph.D.; Kirsten B. Moysich, Ph.D.; John E. Vena, Ph.D.; James R. Marshall, Ph.D.; Saxon Graham, Ph.D., and Rosemary Laughlin, Ph.D., all current or former members of the UB Department of Social and Preventive Medicine.

Also, Takuma Nemoto, M.D., UB clinical associate professor of surgery, and Peter Shields, M.D.; Lea Harty, Ph.D., and Adam Crits, Ph.D., of the Laboratory for Human Carcinogenesis of the National Cancer Institute.

The study was funded by the National Institutes of Health and the Department of Defense Breast Cancer Research Program.