Date Published: 9 October 2006

Scientists discover new breast cancer risk gene

Women with a faulty version of a gene called BRIP1 have an increased risk of developing breast cancer, according to the results of a Cancer Research UK funded study revealed at the National Cancer Research Institute (NCRI) Cancer Conference and published in today's Nature Genetics.

Scientists from The Institute of Cancer Research studied the BRIP1 gene in 1212 women with breast cancer who had a family history of the disease that was not due to the known breast cancer genes, BRCA1 or BRCA2. They compared these women to 2081 healthy people. They found nine BRIP1 faults (mutations) in the breast cancer patients but only two in the healthy individuals. This indicates that the gene is linked to breast cancer more often than would be expected by chance.

The team worked out that carrying a faulty version of BRIP1 doubled a women's risk of the disease ? taking their risk by the age of 70 from one in twelve to around one in six. This discovery could help identify women at increased risk of developing breast cancer, allowing preventative measures to be undertaken and leading to better diagnosis and more tailored treatment in the future.

Inherited genetic faults are estimated to account for up to 25% of familial breast cancer cases. Some of these damaged genes are well known, such as BRCA1 or BRCA2, but the majority of them are as yet unidentified. Scientists decided to look at faults in the BRIP1 gene because it interacts with the known cancer causing gene, BRCA1.

Lead author Nazneen Rahman, professor of cancer genetics at The Institute of Cancer Research, said:

" BRIP1 is the latest gene we have found and leads to a small increased risk of breast cancer. We know there are many more genes still to find before we have the complete picture of the genetic causes of breast cancer, but with each step we are making progress."

Having two faulty copies of the BRIP1 gene is extremely rare and this double genetic fault is a cause of Fanconi anemia ? a childhood disorder that leads to bone marrow failure and leukaemia. This study looked at women who carry just one faulty copy of the BRIP1 gene who, although they are at an increased risk of breast cancer, are otherwise healthy.

BRIP1, like BRCA1 and BRCA2 is a DNA-repair gene, so women with a faulty version of this gene cannot repair damaged DNA correctly. Individuals with faulty DNA-repair genes have an increased risk of cancer because their healthy cells are more likely to accumulate genetic damage that can trigger the cell to replicate uncontrollably ? causing cancer.

Only 0.1% of the general UK population, around 30,000 women, carry a damaged version of the BRIP1 gene. Not all women with this genetic fault will go on to develop breast cancer but the researchers believe this particular genetic fault contributes to around 100 cases of breast cancer diagnosed each year in the UK.

Professor John Toy, Cancer Research UK's medical director, said:

" The discovery of a gene that increases breast cancer risk, even for a small number of women, is very important. Scientists are now beginning to understand more about the genes that are linked to breast cancer and we hope this knowledge will help identify and better manage more women at an increased risk of the disease in the future."

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