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Pregnancy exposures determine risk of breast cancer in multiple generations of offspring
Date:9/11/2012

ats given a high fat diet during pregnancy compared to the offspring of control rats which ate a normal diet during pregnancy. The increased risk did not extend to the great-granddaughters of high-fat fed rats.

"We also found that if the mother was fed a high fat diet before conception and throughout pregnancy, the risk of increased breast cancer was transmitted to granddaughters through either males or females exposed to the high fat diet in utero," says the study's lead investigator, Sonia de Assis, Ph.D., a postdoctoral researcher in Hilakivi-Clarke's laboratory.

In the other group, rats were fed a diet supplemented with estrogen during the last week of pregnancy, and the control rats were fed a normal diet. The researchers found a 50 percent higher incidence of breast tumors in the exposed rats' daughters, granddaughters, and great-granddaughters, compared to the control group. In this case, increased breast cancer risk was transmitted to granddaughters through the in utero estrogen exposed females only.

Both the high-fat and excess estrogen diets produced breast tissue in the affected generations of female offspring that had more than the normal number of terminal end buds, structures that are the building blocks of mammary epithelial tree and primary targets for carcinogens.

The researchers also documented epigenetic changes in the mammary glands of all three generations of pregnant rats exposed to estrogen.

"Germ cells cells involved in reproduction first develop during the fetal period and in utero exposures, such as the ones in our study, could disrupt their normal epigenetic marks and affect how genes are turned on or turned off," de Assis says. "Those alterations then can be passed on and affect the risk of disease, in this case breast cancer, in subsequent generations."

Hilakivi-Clarke points out that two-thirds of human familial breast cancers have no known genetic mutations. She says the effect seen from a high-fat die
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Contact: Karen Mallet
km463@georgetown.edu
Georgetown University Medical Center
Source:Eurekalert

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