Scientists detect long-elusive gene

By Susan Milius

Washington (UPI): Ending a fitful scientific race spanning nearly two decades, an international team of researchers announced Thursday they have found a gene that plays a role in a wide range of cell functions and which may increase the risk of breast cancer five-fold in carriers.

A person who inherits two flawed copies of the gene -- dubbed Atm -- will develop the rare but fatal disease ataxia telengiectasia (At), "but the significance of the gene goes far beyond that," said Yosef Shiloh, who led the collaboration from Tel Aviv University in Israel.

A person who carries one flawed and one normal copy of the gene will not show symptoms of At, but may be at higher risk for cancer. Mothers of At patients, women who presumably have one flawed copy of the gene, have five times more breast cancer than the average.

If Atm does prove to increase the risk of breast cancer, the gene will account for more breast cancer than previously identified breast-cancer genes. The Atm gene would be responsible for up to 8 percent of the cases.

Besides cancer, people with only one copy of the flawed gene may also be especially at risk from exposure to radiation, said Richard Gatti, whose lab at University of California, Los Angeles played a key role in finding the gene.

"This could change all the conventional radiation dosages for treating cancer," he said.

Shiloh, Gatti, Francis Collins, director of the National Center for Human Genome Research at the National Institutes of Health, A.M.R. Taylor from the University of Birmingham and 26 other members of the research collaboration published their findings in this week's edition of the journal Science.

"It was evident from the start that this gene would be very important," Shiloh told United Press International.

He was drawn to work on the disease At when he saw patients for the first time 18 years ago and realized that some underlying factor must connect their seemingly unrelated symptoms, a factor that would probably prove basic to cell function itself.

The disease At frequently shows up first when toddlers have unusual difficulty walking steadily. Wobbling is a sign of deterioration in the brain cerebellum, deterioration that worsens with time. Most of the children need wheelchairs by the time they reach 10 years of age.

Sufferers also have very weak immune systems, as well as a strong tendency to get diabetes and cancer.

"If you treat the cancers with conventional doses of radiation, you will kill the patients," said Gatti. The At patients develop wounds and side-effects from radiation at doses much lower than other people do.

The At patients also show some of the signs of age unusually early. "Last night I saw an eight-year-old Italian girl with At who had strands of gray in her hair," said Gatti.

Few of these patients live past 30.

"I can tell an At patient from a distance," said Shiloh.

"There's an expression on their faces; they're very sad."

Such a wide range of symptoms probably came from a flaw in some system that was common in all or many of the body's tissues, reasoned researchers. "We've assumed for a long time that this would be a housekeeping gene," said Gatti.

"We think the major defect is in the system that takes messages from the outside of the cell to the nucleus," said Shiloh. "In At cells, one of the telephone lines is down."