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Defective Gene Tied to Uterine Fibroids

Discovery raises hope of new therapies for painful condition

SUNDAY, Feb. 24, 2002 (HealthDayNews) -- The identification of a genetic mutation could one day lead to new treatments for fibroids, a common gynecological problem that can cause discomfort, bleeding and reduced fertility.

An international team of scientists has identified a gene mutation linked to a condition called multiple cutaneous and uterine leiomyomatosis, which causes non-cancerous but problematic fibroid tumors in the uterus and skin. Uterine fibroids usually appear in women between the ages of 20 and 35.

In the United States, roughly 30 percent of women develop uterine fibroids during their lifetime, but not every woman will experience the symptoms of pain and bleeding.

Current treatments include drugs that can temporarily shrink the fibroids. But some women require surgical removal of the fibroids or even a hysterectomy, although that procedure is usually a last resort.

According to Dr. Ian P.M. Tomlinson, a researcher with London's Imperial Cancer Research Fund, there had been little medical literature on multiple cutaneous and uterine leiomyomatosis. But there were some reports of fibroids running in families.

At the same time, it appears that some people with multiple cutaneous and uterine leiomyomatosis are also at increased risk of a rare but aggressive cancer called type II papillary renal cell carcinoma.

"We thought that there was a good chance that this was a genetic disorder," says Tomlinson. "We went out and identified families, and it looked very much like it was genetic once we'd done that."

A team led by Dr. Richard Houlston, an expert in cancer genetics at the Institute of Cancer Research in Surrey, England, had narrowed the search for the uterine fibroid gene to chromosome 1 by May 2001. But after learning that Tomlinson's group and another team of researchers in Finland were looking for the same gene, the scientists decided to pool their research and work together.

The result was the identification of the fumarate hydratase, or FH gene, which they describe in the Feb. 25 issue of Nature Genetics.

Normally, the fumarate hydratase gene plays a role in basic cell energy production, and it's commonly referred to as a "housekeeping" gene. Tomlinson says that their findings suggest that fibroid cells have defective energy production.

But the exact mechanism of how mutations in the FH gene lead to fibroids is not as clear, says Tomlinson.

"We know that these people have inherited one copy of the gene that's faulty," he says. "The tumors start off without any or very little function of this [gene]."

Houlston says that identifying the mutated FH gene could help give researchers a better grasp of why uterine fibroids develop.

"It does actually provide a very good model as to why fibroids may develop, and you could manipulate it in a cell system and try and learn more about it," says Houlston.

"In terms of fibroids, if you have a good model system, it's theoretically possible that you could produce therapies and interventions which could have benefits," he adds.

Dr. William Foulkes, an assistant professor of human genetics at McGill University in Montreal, Canada, is familiar with the research, and says that, at first glance, the findings may seem surprising.

"Fumarate hydratase is not exactly a gene you would have immediately thought of as a candidate for diseases as varied as uterine fibroids, skin leiomylomas and papillary renal cell cancer," says Foulkes.

But, he notes, genes located near the FH gene are linked to some hereditary cancers.

He also cites case studies of infants who died quickly because they lacked both copies of the FH gene. And their mothers were found to have skin fibroids characteristic of multiple cutaneous and uterine leiomyomatosis.

Tomlinson says that future studies will look into how the genetic defect leads to fibroids, and study the role of the FH gene in women with uterine fibroids.

"Fibroids are not intrinsically life-threatening," Tomlinson says. But "They're so common they're a very big cause of not only illness [but some deaths], because of the inevitable complications of surgery."

"To have some sort of medical therapy that would allow you to treat these without having to have hysterectomy or removal of the tumors by some other [method] would mean that it would save people a lot of time off work, a lot of illness and also, of course, a lot of expenditure from governments or individuals," Tomlinson adds.

What to Do: Find out more about uterine fibroids from MEDLINEplus, or Brigham and Women's Hospital's Center for Uterine Fibroids.

SOURCES: Interviews with Ian P.M. Tomlinson, M.D., Ph.D., head, Molecular and Population Genetics Research Laboratory, Imperial Cancer Research Fund, London, England; Richard S. Houlston, M.D., Ph.D., researcher, Section of Cancer Genetics, Institute of Cancer Research, Surrey, England; William D. Foulkes, M.D., Ph.D., assistant professor of biochemical and metabolic genetics, Department of Human Genetics, Montreal General Hospital, Montreal, Canada; Feb. 25, 2002, Nature Genetics
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