Moderate drinking increases risk of ER+/PR+ breast cancer

SAN DIEGO-Even one alcoholic drink a day can raise the risk of breast cancer, according to an analysis of 184,418 postmenopausal women in the NIH-AARP Diet and Health Study presented at the 2008 American Association of Cancer Research annual meeting (abstract 4168). The study found a 32% increased risk for ER- and PR-positive tumors among women who reported consuming one or two drinks a day.

“The risk is evident regardless of the type of alcohol consumed,” said Jasmine Lew, a medical student at the University of Chicago School of Medicine. She conducted her research as a recipient of the Howard Hughes Medical Institute-NIH Research Scholarship at the NCI Division of Cancer Epidemiology and Genetics.

“We found that regular consumption of alcohol, even modest amounts, increased the relative risk, especially for the most common type of breast cancer,” she said.

Women were enrolled in the study in 1995 (mean age, 62) and followed for an average of 7 years. Alcohol consumption was reported by 70% of the subjects. Most consumed less than one drink a day.

The risk of breast cancer increased linearly as alcohol consumption increased. Compared with nondrinkers, women who drank less than 5 g a day had a relative risk of 1.04 while those who consumed 45 g or more had a relative risk of 1.38 (P < .01).

The relative risk of ER+/PR+ breast cancer attributable to alcohol increased by more than 50% in women who had three or more alcoholic drinks a day, Ms. Lew reported.

The main hypothesis is that alcohol interferes with estrogen metabolism, leading to changes in cell differentiation and growth, she explained.

“Our findings fit with existing data from other studies, but ours is the largest study to date,” Ms. Lew noted.

Specific genes may be involved

Specific variations within two genes involved with alcohol metabolism are associated with an increased risk of breast cancer, other investigators reported at the meeting (abstract 5814). Researchers from Georgetown University’s Lombardi Comprehensive Cancer Center and the State University of New York at Buffalo found that sequence variations within the genes ADH1B and ADH1C may as much as double the risk among postmenopausal women who consume alcohol.

The findings come from the Western New York Exposure and Breast Cancer Study, a population-based case-control study of breast cancer conducted between 1996 and 2001. Investigators analyzed DNA samples from 991 women with breast cancer and 1,698 controls. They found that risk was associated with variations within the DNA sequences rs1042026 in ADH1B and rs1614972 in ADH1C, which code for the alcohol dehydrogenase enzyme.

One variant doubled the risk among drinkers in a dose-dependent fashion, and the other variant offered a protective effect that was inversely proportional to the level of drinking. Protection was lost as alcohol consumption increased, reported Catalin Marian, MD, PhD, a research instructor of cancer genetics and epidemiology at Georgetown.

“Epidemiologic studies have shown an association between alcohol and breast cancer risk, but the underlying biological mechanisms have not been understood,” Dr. Marian said. “Certain sequence variations can decrease enzymatic activity so that alcohol is not broken down, while others can increase enzymatic activity and thus increase the rate of metabolism. The end-product of this reaction may be toxic, which is a possible mechanism for producing cancer.”