Researchers identify breast cancer risk gene

Cancer Research UK

Inheriting a damaged version of a gene called CHK2 nearly doubles a woman's chance of developing breast cancer, Cancer Research UK scientists report in Nature Genetics.

A faulty version of CHK2 appears to be one of a number of genes that can combine to increase the risk of breast cancer, according to the study, a collaboration between charity-funded researchers at The Institute of Cancer Research and the University of Cambridge, and colleagues in the Netherlands.

Scientists believe the discovery may eventually bring improved genetic testing for breast cancer and could lead to new ways of treating and preventing the disease.

Scientists already know that faults in the BRCA1 and BRCA2 genes greatly increase the chance of developing breast cancer, but these only account for about 2 per cent of cases. They believe inherited risk of breast cancer is more often caused by a combination of genes, each with a modest effect on risk. The new study suggests that a faulty version of CHK2 is one such gene.

Researchers looked at how often women with breast cancer inherited a particular faulty version of the gene called CHK2 1100delC, which has a piece missing. They compared 1071 breast cancer patients who had a family history of the disease, but hadn't inherited BRCA1 or BRCA2, with a second group of 1620 healthy women.

In the patient group, 5.1 per cent had inherited the faulty version, compared with only 1.1 per cent of healthy women. In families where some members had inherited the damaged CHK2 gene, the gene was linked to cases of breast cancer more often than would be expected by chance.

Lead researcher Prof Mike Stratton, of The Institute of Cancer Research, says: "Predisposal to breast cancer often comes from the additive effect of a number of genes, each of which on its own has just a small effect.

"Our research provides the first well substantiated example of one of these additive genes, although we need to learn much more about CHK2 before we can consider using this information in clinical practice."

Scientists also looked at inheritance of CHK2 in families with one or more cases of male breast cancer, which is far rarer than the female form and affects just 250 men each year. The damaged gene was found in 13.5 per cent of these cases, suggesting it substantially increases men's risk of the disease - although because breast cancer is so rare in men, their chance of developing it remains much lower than for women.

They conducted detailed statistical analysis on their data and estimated that the gene raises a women's risk of breast cancer by about two-fold. A man's risk seemed to be increased even more substantially, although the small number of cases of male breast cancer made the increase difficult to estimate precisely.

The gene had no effect on risk in women who had also inherited abnormal versions of BRCA1 or BRCA2. This suggests that it is interacting with the BRCA genes in some way and is likely to be involved in similar processes within the cell. Scientists believe all three genes are involved in helping to repair damage that occurs to the genes within breast cells, which can lead to cancer if left uncorrected.

Fellow researcher Dr Doug Easton, at the Cancer Research UK Genetic Epidemiology Unit in Cambridge, adds: "We believe that CHK2 is involved in repairing genetic damage within a woman's breast, which is why her risk of cancer goes up when the gene goes wrong. But in women with abnormal BRCA genes, the system for repairing genes will already be faulty, so a damaged CHK2 gene cannot further increase her risk."

Dr Easton adds: "This is a very important discovery. By identifying genes that work in combination to raise the risk of breast cancer, we'll gain a much clearer understanding of how the disease develops."

ENDS

Note to Editors:

The Dutch researchers worked at the Erasmus Medical Center in Rotterdam.