UB Scientists Find Breast-Cancer Risk May Be Influenced By Gene That Regulates Serum Triglycerides

ATHENS -- University at Buffalo researchers have shown for the first time that a variant of the apolipoprotein E (apoE) gene, known as apoE 4, may increase the risk of breast cancer by inhibiting the elimination of serum triglycerides from the bloodstream.

While women with the highest triglyceride levels had a slight increase in risk of breast cancer, those with the highest levels, plus the apoE 4 genotype, had a four-fold increase in risk.

"We think that apoE 4 keeps serum triglyceride levels elevated by reducing their clearance," said Kirsten Moysich, Ph.D., a molecular epidemiologist at UB and Roswell Park Cancer Institute, who is working with colleagues from the UB Department of Social and Preventive Medicine. "Triglycerides themselves appear to be a risk factor for breast cancer by reducing sex-hormone-binding globulin levels, which may lead to higher endogenous estrogen levels. This genotype seems to keep levels of triglycerides constantly high."

Moysich presented her findings here today (Sept. 6) at the annual meeting of the International Society for Environmental Epidemiology. The study also has been accepted for publication.

The apoE gene in its three variations -- e2, e3 and e4 -- is involved in lipid metabolism. The e4 variant has been associated with elevated levels of cholesterol and triglycerides, and with an increased risk of coronary disease and Alzheimer's disease, Moysich said.

To determine if apoE 4 also influences the association between serum triglycerides and breast cancer, Moysich and colleagues analyzed blood samples from 256 women with primary breast cancer and 325 controls for triglyceride levels and apoE genotype. Twenty-four percent of the women in the study were found to have the apoE 4 gene.

The results showed no relationship between increased breast-cancer risk and apoE genotype when comparing only genotypes. Women with the highest levels of triglycerides were found to be at a 70-percent-greater risk than women with the lowest levels. But when comparing triglyceride levels and breast-cancer risk among apoE genotypes, triglycerides were associated with elevated risk only in women with the e4 genotype.

Moysich said that if these results can be replicated, researchers will gain further understanding of the role of dietary factors and serum lipids in breast-cancer development.

Also contributing to the study were Julie Baker, a doctoral student, and Jo L. Freudenheim, Ph.D., professor, both in the UB Department of Social and Preventive Medicine; Christine Ambrosone, Ph.D., formerly with UB and now a molecular epidemiologist with the Food and Drug Administration, and Elise Bowman, research associate, and Peter G. Shields, M.D., of the National Cancer Institute.

The study was funded by grants from the National Cancer Institute and the National Institute for Environmental Health and Safety.