Scientists Watch Breast
Cancer Gene at Work
Excerpt By Amy Norton, Reuters Health

NEW YORK (Reuters Health) - Shedding new light on gene-related cases of breast and ovarian cancer, scientists have discovered that a gene linked to both diseases may play a crucial role in repairing genetic damage in body cells.

Researchers have known for several years that mutations in the genes BRCA1 and BRCA2 increase a woman's risk of breast and ovarian cancer. The new research, reported in the May 22nd issue of Proceedings of the National Academy of Sciences, offers clues as to why.

BRCA1 appears to spot and help mend DNA damage that occurs during normal cell division. The implication is that when BRCA1 is mutated, the DNA repair process may eventually go wrong, allowing abnormal cells to proliferate and cancer to begin.

Dr. Tanya T. Paull and her colleagues were able to observe BRCA1's interaction with DNA by genetically engineering human BRCA1 protein and observing it in a test tube. Just creating the protein in the lab has been a significant obstacle for scientists, according to Paull, a researcher at the University of Texas, Austin.

But, she said in an interview with Reuters Health, her team was able to show for the first time that BRCA1 binds directly to cell DNA. Moreover, Paull explained, the gene ``prefers'' to bind to ``unusual'' DNA structures. This strongly suggests BRCA1 is a key player in the DNA repair system, the body's first line of defense against cancer.

Women found to be carriers of a BRCA1 or BRCA2 mutation have one defective copy of the gene and one normal copy. They are more susceptible to cancer, Paull noted, because if something goes wrong with the normal copy, there is nothing left to take over the gene's job.

But why BRCA mutations are linked only to breast and ovarian cancers is a mystery. If BRCA1 is so important to DNA repair, Paull said, ``you'd expect the effects of a mutation to be across the body.''

One theory is that something inherent in breast and ovary cells makes them more susceptible to the loss of a functioning BRCA gene. For example, Paull explained, during puberty breast cells go through a period of rapid division, which could increase the rate of DNA damage within the cells.

While this research is for now ``far removed'' from women who carry BRCA mutations or who have cancer, Paull stressed the importance of understanding what happens at the most basic cellular level during cancer development.

``I think the only way to find cures,'' she said, ``is to understand what's going wrong in the cells.''

SOURCE: Proceedings of the National Academy of Sciences 2001;98:6086-

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