London: Women with mutations in a certain gene have on average a 35 per cent chance of developing breast cancer by the age of 70, scientists have found.
A team of researchers from 17 centres in eight countries led by the University of Cambridge analysed data from 154 families without BRCA1 or BRCA2 mutations, which included 362 family members with PALB2 gene mutations.
Women who carried rare mutations in PALB2 were found to have on average a one in three chance of developing breast cancer by the age of 70. However, the risks were highly dependent on family history of breast cancer where carriers with more relatives affected by breast cancer, were at higher risk. Only a very small proportion of women worldwide carry such mutations and the researchers pointed out that additional studies are required to obtain precise estimates of mutation carrier frequency in the population.
PALB2 is known to interact with both the BRCA1 and BRCA2 and was first linked with breast cancer in 2007. As is the case for women who carry mutations in BRCA1 or BRCA2, women with PALB2 mutations who were born more recently tended to be at a higher risk of developing breast cancer than those born earlier.
The reason why is unclear, but the researchers speculated that it may be related to factors such as later age at first childbirth, smaller families and better surveillance leading to earlier age of diagnosis. "Since the BRCA1 and BRCA2 mutations were discovered in the mid-90s, no other genes of similar importance have been found and the consensus in the scientific community if more exist we would have found them by now," said Dr Marc
Tischkowitz from the Department of Medical Genetics at the University of Cambridge, who led the study. "PALB2 is a potential candidate to be 'BRCA3'. As mutations in this gene are uncommon, obtaining accurate risk figures is only possible through large international collaborations like this. "Now that we have identified this gene, we are in a position to provide genetic counselling and advice. If a woman is found to carry this mutation, we would recommend additional surveillance, such as MRI breast screening," said Tischkowitz.
The researchers at Addenbrooke's Hospital, part of Cambridge University National Health Service Hospitals Trust, have developed a clinical test for PALB2. There is evidence that cells carrying the PALB2 mutation are sensitive to a new class of drugs known as PARP inhibitors that are currently being trialled in BRCA1/2-related breast cancers, researchers said. It is possible that these drugs would also work in PALB2-related breast cancer.
