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Genes Linked to Uterine Fibroids

Three are passed from father to daughter, researchers say

FRIDAY, July 26, 2002 (HealthDayNews) -- Researchers have identified 145 genes -- three of which are passed from father to daughter -- that are involved in the development and growth of uterine fibroids.

The findings, which appear in the July issue of Fertility and Sterility, are a significant step in the quest to find the cause or causes of uterine fibroids and could lead to new targets for treatments, the researchers say.

Lead author John Tsibris likens the discovery to General Patton surveying enemy lines through binoculars during World War II, then suddenly being handed a satellite photo of the whole battlefield.

"These are the first satellite photos. It's a conceptual breakthrough at the beginning of the new century where we find that, in addition to estrogen and progesterone, we're looking at new players such as retinoic acids and maybe new targets," says Tsibris, a professor of obstetrics and gynecology at the University of South Florida in Tampa.

"We are having an unexpected overview of the tumor process," he adds.

Tsibris worked with Dr. James Segars of the National Institute of Child Health and Human Development and other scientists from the University of South Florida.

"Although uterine fibroids are extremely common, little is known about why and how they develop," Dr. Duane Alexander, director of the institute, says in a prepared statement. "This study helps us better understand how fibroids grow, and may lead to the development of a variety of new therapies to treat women who have them."

Uterine fibroids are noncancerous tumors that affect up to 70 percent of women of reproductive age and can cause uterine bleeding, pain and even infertility. Estrogen and progesterone are known to play a role in the development of fibroids, but the exact cause remains unknown.

"The triggering factor is not known," says Dr. Ernst G. Bartsich, a clinical associate professor of obstetrics and gynecology at New York Weill Cornell Medical Center in New York City.

In the new study, Tsibris and his colleagues used "microarray analysis" to screen 12,000 genes in uterine tissue (both normal and abnormal) taken from nine women, to compare genes in fibroids with those found in normal uterine muscle. The team ended up with 145 genes that were either more active or less active in the tumors.

The more active genes appear to support the growth of tumors, while the less active ones contribute to normal function, the researchers say.

"This is the first time that such a large-scale screening of fibroids has been done," Tsibris says. "It revealed that there are other potential regulators of fibroid growth, in addition to estrogens, progesterone and retinoic acid known until now."

The researchers also found three of the more active genes are passed from father to daughter.

"If the genes are important for growth, it means a woman's susceptibility to fibroids comes from her father's side of the family," Tsibris says.

Surprisingly, some of the active genes were "out of place," meaning genes previously thought only to be involved in mental retardation or nervous system function are also active in fibroids, Tsibris says.

This study is just the tip of the genetic iceberg, health experts say.

"We long suspected that genetic factors were involved in the development of fibroids," Bartsich says. "[But] we still don't know the exact triggering mechanism. If there was a protein that would be instrumental in developing fibroids, then it might be a way to find a counter mechanism. But at the present time, it seems to me to be a little bit far. It's a good direction, but to put it into practice, it might be a long way to go."

If it weren't for the Human Genome Project, Tsibris says, scientists would be even further away from finding new therapeutic targets: "That's the beauty of it. We could have been working for another 10 or 15 years, and nobody in their right mind would have thought to look at these genes."

Now that the genes have been identified, "the next step is to look at the proteins produced from these genes, and learn how they interact with each other to sustain tumor growth," Tsibris says.

"Starting from human genes, we will learn the main regulators of tumor growth, and become very efficient in selecting targets for new, non-surgical therapies sometime in the next few years," he says.

When those therapies come, they will likely be in the area of prevention, Bartsich says.

What To Do

To learn more about uterine fibroids, visit the National Library of Medicine. For more information on different treatment choices for fibroids, visit Fibroid Choice, which is put together by Bartsich.

SOURCES: John Tsibris, Ph.D., professor, obstetrics and gynecology, University of South Florida, Tampa; Ernst G. Bartsich, M.D., clinical associate professor, obstetrics and gynecology, New York Weill Cornell Medical Center, New York City; July 2002 Fertility and Sterility
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