Early Life Exposure Predicts Uterine Tumors

Environmental Agents Cause Adult Cancer in Animals

In a unique animal study, scientists found that rats susceptible to developing uterine tumors inevitably did so when exposed to an environmental toxin just three days after birth.

A single, three-day exposure was enough to "reprogram" the uterus to respond to normal hormonal signals in a way that promoted tumor growth.

The researchers theorize this new model of gene-environment interaction may go some way in explaining why, in a population of people at the same genetic risk, some develop cancer and others don't.

Genetic susceptibility

"In genetically susceptible individuals, exposures that occur early in life may have as great or greater an impact on tumor outcome as those that occur during their adult life," says the study's first author, Jennifer Cook, a graduate student in M. D. Anderson's Science Park Research Division in Smithville, Texas. The study findings were presented last month at the annual meeting of the American Association for Cancer Research (AACR).

Molecular biologist Cheryl Walker, Ph.D., the principal investigator on the study and professor of carcinogenesis at M. D. Anderson, says the finding "establishes developmental programming as a novel type of gene-environment interaction."

In the experiment, Cook, Walker and a team of other researchers used rats genetically susceptible to developing uterine leiomyomas, the same kind of benign fibroid tumors that many women have. They exposed these rats to a known environmental estrogen, DES, three to five days after birth, a crucial period in development of the animals' reproductive tract. As adults, a little more than half of the genetically predisposed rats developed tumors, compared to 100% of DES-exposed rats.

Common gene defect

Then, researchers looked at how uterine tissue in exposed animals responded to normal hormones, and found that "the expression of genes regulated by hormones was abnormally high much of the time," Cook says.

"A short exposure to an environmental estrogen reprogrammed the tissue to be super sensitive to hormones, which drives development of these tumors."

All of the rats shared a common defect in a tumor suppressor gene and had the same genetic susceptibility to developing fibroids, but exposure to the environmental estrogen changed the probability of the tumor suppressor gene appearing in the body, and this could theoretically happen within any susceptible population," Walker says.

"Hypothetically, environmental exposure during development of other organs such as the breast could change the presence of human tumor susceptibility genes such as BRCA1," she says. "This could offer a clue as to why some women with inherited BRCA1 mutations develop cancer, while others don't."