Possible Evolutionary Advantage Seen in Breast Cancer Genes

SEATTLE--"Is it possible that at some point in human evolution,there was some selective advantage of BRCA1 and BRCA2?" Mary-ClaireKing, PhD, asked during her presentation at the annual meeting of the AmericanAssociation for the Advancement of Science (AAAS).

These breast cancer genes may have offered a very important evolutionaryadvantage--increased lactation--suggested Dr. King, professor of medicineand genetics, University of Washington.

Dr. King noted that the normal copy of the gene works to control cellproliferation in the breasts, ovaries, and prostate. A mutation that knockedout that control could increase lactation, among other consequences.

For societies living on subsistence diets, "anything that stimulateslactation would be a benefit," she said. This potential advantageof old, however, "has no meaning for the young woman in the modernera."

While inherited BRCA1 and BRCA2 mutations cause only a small fractionof breast cancers, they offer important opportunities to further understandthe genetics of cancer in both sexes.

Dr. King described one BRCA2 family in which breast cancer struck thefemale members often, as one would expect. But five males in the familyalso developed the disease, quite evidently from inheriting the gene.

She also noted increasing evidence that the two breast cancer genescan be a cause of prostate cancer, with BRCA2 probably playing a biggerrole.

In her AAAS presentation, Dr. King described two women from a hereditarybreast cancer family that she has been studying for many years.

The two sisters had prophylactic mastectomies more than 10 years ago,well before the discovery of BRCA1 and the development of a test for thegene.

It fell to Dr. King to eventually tell each sister that she had notinherited the family's cancer gene. Somewhat to her surprise, the firstresponse from both women was: "Thank God, I don't have to worry aboutmy daughter." And both women felt they had made a rational decisionin having their breasts removed, given the information available to themat the time

A recent discovery related to colon cancer has pointed a new directionfor breast cancer genetics, Dr. King said. People with the APC gene, agene linked to inherited colon cancer, do not all suffer disease of identicalseverity, nor do mice who inherit a similar gene.

Researchers working with mice discovered that a second gene acts tomodify the effect of the APC gene. A counterpart to the mouse modifiergene has now been identified in humans.

"We're not at that point in breast cancer yet, but some day wewill be," Dr. King predicted.

Gene Therapy

At the same AAAS session, in a presentation on gene therapy, Mark A.Kay, MD, PhD, of the University of Washington, noted that the emphasishas moved from experimental treatments of single-gene inherited diseasesto trials for such common illnesses as cancer, heart disease, and diabetes.Of some 150 gene therapy trials to date, most have targeted "nongenetic"diseases, he said. The shift largely stems from the pharmaceutical industry'sexpanding interest in diseases with greater market value, he said, withcancer an important target.