High-fat diet during pregnancy could influence breast cancer risk for up to three generations

Paul Basilio, MDLinx | July 05, 2017

A team of researchers led by scientists at the Georgetown Lombardi Comprehensive Cancer Center in Washington, DC, have found that female mice fed a diet high in fat derived from corn oil showed genetic changes that increased breast cancer susceptibility across generations of female offspring.

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The amount of fat fed to the mice in the experiment matched a common human diet.

The study, which was recently published in the journal Breast Cancer Research, suggests a new research direction when examining the diets of pregnant women, according to Leena Hilakivi-Clarke, PhD, the study’s lead author and a Professor of Oncology at Georgetown Lombardi.

“It is believed that environmental and life-style 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,” Dr. Hilakivi-Clarke said.

She added that a high-fat diet is associated with increased inflammation and risk for cancer.

In previous research, Dr. Hilakivi-Clarke found that mice that ate a high-fat diet while pregnant had female offspring that were at increased risk of breast cancer.

The current study found that when pregnant mice were switched to a high-fat diet during the second trimester, an increased risk of breast cancer was seen in the third generation as well. The second trimester is typically when the germ line that mediates genetic information from one generation to another form in the fetus.

A number of genetic changes were present in the first (daughter) and third (great-granddaughter) generations of mice fed the high-fat diet. Several changes have been linked to increased breast cancer risk, increased resistance to cancer treatment, poor cancer prognosis, and impaired anti-cancer immunity in women.

Researchers also found three times as many genetic changes in the third vs first generation mammary tissue when comparing the high-fat diet progeny and the control group’s offspring.

“The soil in the breast, so to speak, remained fertile for breast cancer development in our high-fat experimental mice,” Dr. Hilakivi-Clarke explained.

She noted that the amount of fat fed to the experimental mice mirrored a common human diet. In the study, both the control mice and the mice fed chow with high levels of corn oil ate the same amount of calories and they weighed the same.

“Our experimental mice got 40% of their energy from fat, and the control mice got a normal diet that provided 18% of their energy from fat,” Dr. Hilakivi-Clarke said. “The typical human diet now consists of 33% fat.”

Pregnant mice in the experimental arm ate the high-fat diet starting at gestation day 10. That is the time when a daughter’s ovarian eggs (and their 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 heritable changes in the germ cells.

“Studies have shown that pregnant women consume more fats than non-pregnant women, and the increase takes place between the first and second trimester,” she said. “Of the 1.7 million new cases of breast cancer diagnosed in 2012, 90% had no known causes. Putting these facts and our findings together really does give food for thought.”

The study was supported by National Institutes of Health. For more information, click here

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