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Genetic propensity to common cancers found.

Genetic propensity to common cancers found

Researchers have identified an inherited gene defect that heavily predisposes individuals to breast cancer and some other malignancies. Cancer scientists say the finding provides a new window on the molecular underpinnings of hereditary cancers and should lead to tests that identify people likely to get the diseases.

"All this will presumably be extremely helpful in early diagnosis of people at risk," says David Malkin of the Massachusetts General Hospital Cancer Center in Boston, who participated in the research effort. "We'll be able to say, 'Yes, you carry this mutation . . . and you are at risk,' or 'No, you don't.'"

Early diagnosis and treatment provides the best insurance against death from cancer, Malkin and others note. In the case of breast cancer, women who recognize they are at high risk may initiate a range of options from frequent breast exams to hormonal therapy to -- in extreme cases -- preemptive mastectomy.

The discovery emerged in a study of a rare syndrome called Li-Fraumeni. Family members who inherit the condition have healthy childhoods. By age 30, however, nearly 50 percent develop one or more of several different cancers, including brain tumors, osteosarcoma, leukemia, and especially breast cancer. More than 90 percent develop cancer by age 70. In the Nov. 30 SCIENCE, Malkin and researchers at four U.S. medical centers describe five Li-Fraumeni families in which individuals with syndrome-linked cancers all carry inherited mutant versions of a gene called p53, while most unaffected members do not.

"It's a very important finding," says Alfred G. Knudson of the Fox Chase Cancer Center in Philadelphia, who has followed the work. Until now, he says, the only gene defects known to cause adult cancers were those that accumulated through a lifetime. "Now for the first time we have a gene in the germ line shown to be a high risk factor for a common adult cancer, namely breast cancer."

Scientists are familiar with the p53 gene, which in its normal form helps control cell division and prevent cancer. Indeed, researchers frequently find damaged p53 genes in tumor cells from noninherited cancers, but the gene's role in inherited cancers went unrecognized. The question, Knudson explains, has been whether p53 simply exacerbates the effects of other cancer-causing genes or whether it's a major player on its own. He says the new study "shows that it can be very, very critical indeed."

Malkin says he and others are now screening broader populations of cancer victims to see what percentage of various malignancies may be due to flawed p53 genes. "We're not suggesting that every familial cancer syndrome involves p53," he says. "But the data suggest it may be a very important player in breast cancer."

Still, says co-author Stephen H. Friend of Massachusetts General, "People shouldn't think that p53 is the gene for hereditary breast cancer, because there are likely to be several of them. We have no idea what various genes may be responsible for this very heterogeneous group of diseases we call hereditary breast cancer."
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Author:Weiss, Rick
Publication:Science News
Date:Dec 1, 1990
Words:502
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