Exposure to excess estrogen during pregnancy, in mice, increased the risk of breast cancer in their daughter mice, granddaughter mice, and great-granddaughter mice.
PROBLEM: Since yesterday's study involved risks of cancer in the testicles, today's study is an equal opportunity cancer research story. Researchers have previously looked at increased risk of breast cancer in the offspring of women who are exposed to high levels of
estrogen. During pregnancy, exposure to oestradiol (the most potent of human estrogens) and high-fat intake (which increases the body's estrogen levels) have both been shown to cause this effect in first- generation offspring. Demonstrating that environmental damage can be passed on throughout multiple generations, though, would indicate that the mechanism behind the increased risk is epigenetic -- meaning that the environmental factors alter the offspring's gene expression.
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METHODOLOGY: Researchers at Virginia Tech and Georgetown University fed pregnant lab mice either a control or high-fat (mostly corn oil) diet throughout gestation. Other pregnant lab mice were given the control diet supplemented with synthetic oestradiol (EE2). Three subsequent generations were produced, with all offspring kept on the control diet. Mixing things up in order to trace how the risk of breast cancer might be passed down through the generations, the researchers mated unexposed females with exposed males, and vice versa. They induced female offspring with breast tumors after 50 days and recorded the occurrence and frequency of malignancies.
RESULTS: As expected, the daughters of mice exposed to EE2 or fed high-fat diets had higher incidence and multiplicity of mammary tumors than the daughters of the controls. In the granddaughters of the mice on high-fat diets, tumor incidence was also higher, although multiplicity was not. Their great-granddaughters did not have any higher risk of breast cancer. The granddaughters of the EE2-exposed mice, on the other hand, did not have an increased risk of breast cancer, but their daughters (the EE2 mice's great-granddaughters) had a significantly higher frequency of malignancies. Mothers and fathers who themselves had been exposed to high-fat diets in utero produced offspring with an increased risk of breast cancer, but the effects of EE2 exposure were only passed on through the female germ line.
CONCLUSION: An animal model demonstrates that high-fat diets and exposure to environmental estrogen during pregnancy cause an increased risk of breast cancer that extends through multiple generations. A closer look at the mice's DNA indicated that methylation -- a key process in gene expression -- occurred differently in mice with an increased risk of cancer, suggesting that this risk was passed on not due to DNA mutations, but through epigenetic means. So, yet more reason to eat a low-fat diet and avoid exogenous estrogen during pregnancy -- and hope that your grandmother did, too.
The full study, "High-fat or ethinyl-oestradiol intake during pregnancy increases mammary cancer risk in several generation of offspring ," is published in the journal Nature Communications.
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