Potential BRCA3 found

A third gene related to breast cancer risk has been identified by an international team of researchers. Women with mutations in the PALB2 gene have on average a one in three chance of developing breast cancer by the age of 70, and researchers suggest it is a ‘potential candidate to be BRCA3’. Led by Dr Marc Tischkowitz from the University of Cambridge, researchers analysed data from 154 families without BRCA1 and BRCA2, including 362 family members with PALB2 gene mutations. Analysis revealed women carrying rare mutations in the gene had on average a 35% chance of developing breast cancer by the age of 70. However, risks were dependent on family history with carriers with more relatives affected by breast cancer at higher risk. PALB2 – Partner and localiser of BRCA2 – is known to interact with BRCA1 and BRCA2 and was first linked to breast cancer in 2007. As with BRCA1 and BRCA2, women with PALB2 mutations who were born more recently tended to be at a higher risk of developing the disease than those born earlier. Researchers speculate this is linked to later age at first childbirth, smaller families and better surveillance leading to earlier age diagnosis. Only a small proportion of women carry such mutations and the researchers note that further study is required to obtain precise estimates of mutation carrier frequency in the population. “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 is if more exists we would have found them by now,” said Tischkowitz. “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.” Researchers at Addenbrooke’s Hospital have developed a clinical test for PALB2 which will become part of their NHS testing. Evidence suggest that cells carrying the mutation are sensitive to a new class of drugs called PARP inhibitors currently being trialled in BRCA1/2-related breast cancers and. they may also work in PALB2-related breast cancers