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September 29, 1997

Genetic research offers some promise for cancer treatment, speaker says

Chancellor Greenwood, with Mary-Claire King before King's public lecture at the Music Center Recital Hall on September 19.
By Robert Irion

Small-scale medical trials on cancer patients provide hope that gene therapy could become a potent weapon in the fight against certain ovarian cancers and breast cancers, an audience learned at UCSC on September 19.

University of Washington medical geneticist Mary-Claire King spoke to about 200 people at the Music Center Recital Hall in a public lecture cosponsored by UCSC and the American Cancer Society. In her talk, "Genetic Analysis of Breast and Ovarian Cancer," King reviewed the evidence--much of it found by her team--that genetically inherited mutations trigger about 10 percent of all cases of these devastating diseases in women.

"If we can learn about the genes that are critical to the normal development of these cells through studying families in which the genes have gone awry, then we can learn more about these cancers in general," King said.

King revealed the details of a federally approved, "phase I" clinical trial on 12 women with terminal ovarian cancer, caused in each case by a genetic predisposition to the disease. When researchers introduced large amounts of the healthy, unmutated gene into the women's peritoneal cavities, King said, many of their ovarian tumors stopped growing. Her team will publish the results in November.

The gene of concern is called BRCA1, pinpointed by King and others in 1990 as playing a role in some breast and ovarian cancers. She and her colleagues have since shown that mutations in a related gene, called BRCA2, also contribute to cancer development. The U.S. Food and Drug Administration has granted permission to King's team for a "phase II" gene therapy clinical trial on a larger number of women with ovarian cancer, as well as for a phase I trial on women with advanced BRCA1-related breast cancer.

Overall, King said, our understanding of the genesis of breast and ovarian cancer remains poor. For instance, physicians and researchers are uncertain why the risks of contracting breast cancer continue to rise for women in developed countries, especially the U.S., Canada, and in Europe. "Our grandmothers had far lower risks of getting breast cancer than we do now," she said. "That change is not due to inherited genetics."

Indeed, King noted, the risk of women in the audience's social class developing breast cancer is the same as the risk of a two-pack-a-day smoker getting lung cancer, a statistic that startled her listeners.

The major risk factors, King observed, appear to be earlier onsets of menstruation, later ages of childbearing, and later onsets of menopause. Most notably, diet, exercise, and overall good health among girls have pushed initial menstruations to younger ages, while higher education and job pressures force women to start their families later in life. That leaves more time for estrogen and other hormones to affect the breasts and other tissues in ways that scientists do not yet grasp.

"In some way, our technology has brought with it a change in lifestyle and an increase in the rate of breast cancer," King said. "It is our responsibility to use this technology we have now mastered and bring it to bear on the problem of cancer."

King's talk was part of the American Cancer Society's first Schilling Research Conference, funded by a $1.6 million bequest to the society from the late Col. Frank K. Schilling of Santa Cruz in honor of his wife, Else H. "Henny" Schilling. UCSC professor of biology Frank Talamantes, who also conducts federally funded research on breast cancer, helped to arrange King's visit to UCSC.

For more information about King's research, see " Putting the Puzzle Together," a recent article about her laboratory in the University of Washington's alumni magazine.


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