Genes Involved With Alcohol Metabolism Associated With Increased Risk For Breast Cancer, Study Suggests

The work, conducted by research groups led by Peter Shields, M.D., professor of medicine and oncology at Georgetown University's Lombardi Comprehensive Cancer Center and Jo Freudenheim, Ph.D., chair of social and preventive medicine at the State University of New York at Buffalo, indicates that sequence variations within the genes ADH1B and ADH1C may as much as double a postmenopausal woman drinker's risk for breast cancer.

"We found that variations in two genes coding for the alcohol dehydrogenase enzyme increase the risk of breast cancer among women who drink," said lead author Catalin Marian, M.D., Ph.D., a research instructor of cancer genetics and epidemiology at Georgetown. "The higher their alcohol consumption, the higher their risk."

Marian and colleagues evaluated data from participants in the Western New York Exposure and Breast Cancer (WEB) Study, a population-based case-control study of breast cancer conducted by Freudenheim in women ages 35 to 79 from two western New York counties between 1996 and 2001. Women with primary, histologically confirmed breast cancer served as cases. Healthy control participants were randomly selected and matched to cases by age, race and county of residence.

The research team analyzed DNA samples taken from 991 women with breast cancer and 1,698 controls. They found that variations within the DNA sequences rs1042026 in the gene ADH1B and rs1614972 in the gene ADH1C were associated with an increased breast cancer risk for postmenopausal women. Within the rs1042026 sequence, the risk of breast cancer for women who had a variant form of the gene and who drank alcohol was nearly twice that of women who abstained. The risk of breast cancer increased with the level of alcohol consumption.

Within the rs1614972 sequence, the variant form of the gene offered a protective effect against breast cancer that varied inversely proportional with the drinking level. The more alcohol women drank, the less protective the effect and the higher their risk of developing breast cancer.

Marian cautions that the work needs to be explored further and replicated by other studies, as the research showed these sequence variations were associated with increased risk of breast cancer but were not necessarily biologically responsible for this effect.

"These two genes encode for enzymes involved in the metabolization of alcohol, so variations in these genes can increase or decrease the rate of alcohol metabolism," Marian said. "We have to keep in mind that the gene sequence variations we observed are not located directly in coding regions, but they may be associated and inherited together with other variations that have this effect on the enzyme function."

This research was presented at the American Association for Cancer Research 2008 Annual Meeting, April 12-16.