Fat’s Lasting Impact

Animal study finds high-fat diet in second trimester increases breast cancer risk over generations.

Feeding pregnant female mice a diet high in fat derived from common corn oil resulted in genetic changes that substantially increased breast cancer susceptibility in three generations of female offspring, reports a team of researchers led by scientists at Georgetown Lombardi Comprehensive Cancer Center.

The study suggests a research direction for examining the diet of pregnant women, says the study’s senior author, Leena Hilakivi- Clarke, PhD, professor of oncology.

“It is believed that environmental and lifestyle factors, such as diet, play a critical role in increasing human breast cancer risk, and so we use animal models to reveal the biological mechanisms responsible for the increase in risk in women and their female progeny,” says Hilakivi-Clarke.

A high-fat diet is linked to excess inflammation, and studies connect inflammation and cancer risk, she says.

In earlier studies, Hilakivi-Clarke found that when pregnant mice eat a high-fat diet, they produce “daughters” with an excess risk of the cancer. This study, however, found that if pregnant mice were switched to a high-fat diet during their second trimester, when the germ line mediating genetic information from one generation to another forms in the fetus, an increase in breast cancer risk is also seen in “great granddaughters.”

A gene screen revealed a number of genetic changes in the first (daughter) and third (great granddaughter) high-fat mice generations, including several linked to increased breast cancer in women, increased resistance to treatment, poor prognosis, and impaired anticancer immunity. The researchers also found three times as many genetic changes in third generation than in first generation mammary tissue between high-fat diet progeny and the control group’s offspring.

The amount of fat fed to the experimental mice matched what a human might eat daily, says Hilakivi-Clarke. In the study, both the control mice and the mice fed high levels of corn oil ate the same amount of total calories and they weighed the same. “But our experimental mice got 40 percent of their energy from fat, and the control mice got a normal diet that provided 18 percent of their energy from fat,” she notes. “The typical human diet now consists of 33 percent fat.”

Pregnant mice ate the high-fat diet starting at gestation day 10, the time when a daughter’s ovarian eggs (and germ cells) begin to develop. This corresponds roughly to a woman’s second trimester. By comparison, eating a high-fat diet before and during pregnancy increases breast cancer risk in the subsequent two generations, but does not cause inheritable changes in the germ cells, Hilakivi-Clarke says.