Researchers have discovered an inborn genetic mutation that strongly predisposes people to breast cancer and at least six other malignancies.
Although mutations for several rare childhood cancers have been identified, the new finding is the first detection of an inborn mutation that helps cause one of the biggest cancer killers of adults.
Thus far, the mutation has only been analyzed in a specific hereditary cancer syndrome that afflicts a few hundred families around the world. But scientists believe that the genetic error could play a role in other instances of breast cancer, particularly in those families where more than one woman is afflicted, or when a woman contracts the tumor under the age of 35.
The inherited mutation could also explain clusters of other types of cancer seen in families.
"I think it's very exciting," said Dr. Alfred Knudson of the Fox Chase Cancer Center in Philadelphia, who is familiar with the new work and has long studied the genetics of cancer.
"It's the first time a gene has been identified that predisposes people to a major cancer. And it predisposes people to breast cancer so strongly that it must be a very important step" in the genesis of the tumor.
Scientists hope that when theydetermine how frequent the inborn error is in the population, they can eventually use the gene to identify those who might be at great risk for breast and other types of cancer.
Among carriers of the genetic mutation, the risk is extraordinarily high. The new research indicates that those born with the mutation have a 90 percent chance of developing breast cancer or another type of malignancy by the age of 60, and often much earlier.
Researchers say that people found to harbor the mutation could be counseled to be extra vigilant about watching for signs of cancer in its early stages, when it is most easily treated.
Carriers might even consider preventive treatments, such as certain types of prophylactic chemotherapy and hormone medications now being tried in women who do not yet have breast cancer but are known, from family history, to be at high risk for the disease.
But the researchers, who report the new findings in today's issue of the journal Science, emphasize that the work is too preliminary to be of use to women who have a family history of breast cancer and are concerned about their own risk.
"We're not at all set up for doing that sort of screening yet," said Dr. Stephen H. Friend of Massachusetts General Hospital in Boston, who led the team that detected the inborn mutation.
"These are very intriguing results, but any consideration of doing this for specific individuals will have to wait until we know the frequency of the mutation." He predicted that scientists would know far more about the genetic flaw within the next six months to a year.
The hereditary mutation affects a gene known as p53. The gene normally operates in the body to stanch the growth of tumors and thus belongs to a class of genes known as tumor suppressor genes.
Researchers had already suspected that p53 was extremely important in human cancer because they had detected mutant copies of it in an overwhelming percentage of human tumor samples from a broad variety of organs. The mutations probably arose as people encountered toxins, radioactivity and other carcinogens in the environment.
The flaws were found to knock out the activity of the p53 gene, thereby eliminating from the cell one crucial safeguard against untrammeled growth. Scientists knew that three to seven additional genetic mutations were needed to transform a normal cell into a malignant one, but a mutation in p53 seemed to be a vital step.
The new work is exciting because researchers have now discovered the mutation not just in tumor cells but in every cell of the body. Carriers of the mutation have what is known as a germline mutation, meaning that all cells are equally afflicted and that carriers can pass the defect along to their children.
Carriers must suffer additional genetic damage before one of their body cells can turn malignant, but Dr. Friend and his colleagues have determined that the inborn p53 mutation is such a powerful susceptibility factor that a carrier will almost surely develop cancer at some point in life.