British researchers are a step closer to understanding exactly why the breast cancer susceptibility gene BRCA1 gives women such a high chance of developing the disease.

The new research suggests that in healthy women BRCA1 is involved in the immune system, helping the body look out for cells that may be cancerous and forcing them to self-destruct. But when BRCA1 is faulty, this surveillance system becomes blind to the presence of cancer cells, allowing a tumor to develop.

Women who have a fault in the BRCA1 gene have between a 65 and an 85 per cent chance of developing the disease at some point in their lives, and they have an elevated risk of ovarian cancer. (Faults in BRCA1 and the other major breast cancer susceptibility gene BRCA2 are believed to account for between two and five percent of all breast cancers.)

Scientists already knew that BRCA1 was important in repairing gene damage that can lead to cancer, but the new work by Dr. Paul Harkins and colleagues at Queen's University Belfast suggests that BRCA1 is also involved in spotting damaged cells.

Professor Patrick Johnston, the Director of the Cancer Research Centre at Queen's University in Belfast, explains: "These results are beginning to shed light on why some women have such a high risk of developing breast cancer.

"We already know that a fault in BRCA1 can affect the body's ability to repair gene damage, but this alone may not be enough to explain such a high risk. Now we can see that the faulty gene also impairs the body's ability to spot cells that are becoming cancerous. This combination of problems may explain the gene's devastating effects."

The researchers used a cutting-edge technique called microarray technology. This procedure allows scientists to look at thousands of genes at once to find out which ones are switched on under different circumstances. In this case they compared normal cells with cells that had an overactive BRCA1 gene.

One of the study authors, Heather Andrews, also from Queen's University, explains: "Our results showed that BRCA1 interacts with a specific part of the body's immune system - a chemical called interferon gamma.

"This chemical acts as the eyes and ears of the immune system, scouring the body for diseased cells. The immune system then forces these cells to self- destruct, preventing the growth of a tumor."

In cells from breast tumors where the BRCA1 gene is dysfunctional, the researchers discovered that this interferon gamma surveillance seems to break down. However, by adding a healthy copy of the BRCA1 gene they were able to restore the surveillance system.

SOURCES:
Journal of Biological Chemistry, July 19, 2002
Cancer Research UK (http://www.cancerresearchuk.org)