Breast cancer: Maternal high-fat diet raises risk across generations

New research conducted on pregnant female mice shows that exposure to a high-fat diet can increase the risk of breast cancer across generations. These findings may consolidate understanding of breast cancer factors and help to improve prevention.

Breast cancer is the second most widespread type of cancer among women in the United States, according to the American Cancer Society (ACS), who estimate that there will be around 40,610 deaths attributed to this type of cancer in 2017.

The known causes of lifestyle-related breast cancer have so far included alcohol consumption, lack of physical exercise, obesity, choice of contraceptives, hormone therapy, and breast-feeding. The new research may add an imbalanced diet during pregnancy to this list.

A new study carried out by the Georgetown Lombardi Comprehensive Cancer Center in Washington, D.C., suggests that eating foods that are high in fat during pregnancy may affect the risk of developing breast cancer in female offspring across generations.

Senior study author Leena Hilakivi-Clarke, Ph.D., a professor of oncology at Georgetown Lombardi, and colleagues recently reported their findings in the journal Breast Cancer Research.

Testing a high-fat diet in mice

To study the intergenerational impact of diet, the mice specimens were mated in two different phases. In the first phase of the experiment, the pregnant female mice were randomly divided into one of two groups after mating.

The females in the first group were fed a diet with a normal fat intake, with 16 percent of its calories taken from fat, while those in the second group were fed a high-fat diet.

The high-fat diet took just over 41 percent of its calories from fat. Around 39 percent of these calories came from corn oil, while roughly 2 percent of the calories came from soybean oil.

Since the gestation period in mice is around 19 to 21 days, the controlled feeding of the second group started on day 10 of their pregnancy, which roughly corresponds to the second trimester of pregnancy in humans, a point at which the ovaries of the female fetus begin to develop.

The offspring and further generations that resulted from this phase of the experiment were placed on a normal diet.

High-fat diet caused genetic changes

In the second phase of the experiment, the female offspring that resulted from the previous phase (first-generation offspring) were mated with males fed a high-fat diet. All the females that fell pregnant in this stage were fed a normal diet.

It was observed that first- and third-generation female offspring, or daughters and great-granddaughters, that had been exposed to a high-fat diet through their mothers were at an increased risk of developing breast cancer, and that malignant tumors settled earlier in these generations.

Some differences in the genetic structure of first- and third-generation offspring were also found. Tests revealed that third-generation female mice presented three times more changes in the genetic makeup of their mammary glands when compared with first-generation female mice.

This finding suggests that direct exposure in the womb to a genetic makeup already susceptible to an increased threat of malign tumors amplifies the risk of breast cancer development over generations.

"The soil in the breast, so to speak, remained fertile for breast cancer development in our high-fat experimental mice," says Prof. Hilakivi-Clarke.

Implications for breast cancer

"Studies have shown that pregnant women consume more fats than non-pregnant women, and the increase takes place between the first and second trimester," adds Prof. Hilakivi-Clarke.

This knowledge, combined with the results of the study, suggests that more attention should be paid to women's intake of fatty foods during pregnancy, in light of the potential links between gestational diet and the risk of breast cancer in future generations.

According to the ACS, there are currently more than 3.1 million breast cancer survivors in the U.S. Risk factors and preventability are often a point of contention among specialists. Some factors, such as induced abortion, have been disproven, while others, including smoking, are still being considered.

Studies such as this provide hope that preventability, as well as the survivor ratio, will increase with time, as specialists gain a better understanding of the avertible causes of breast cancer.

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