Gene mutations more likely to cause cancer
A study part-funded by the European Research Council has revealed that women with mutations in the PALB2 gene have on average a one in three chance of developing breast cancer by the age of 70.
In a study run through the international PALB2 Interest Group, a team of researchers from 17 centres in eight countries, led by the UK’s 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 35% chance of developing breast cancer by the age of 70. However, the risks were highly dependent on their family histories 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 point 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 speculate that it may be related to factors such as later age at first childbirth, smaller families and better surveillance leading to an earlier age of diagnosis.
Dr Marc Tischkowitz from the Department of Medical Genetics at the University of Cambridge, who led the study, said: “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. PALB2 is a potential candidate to be ‘BRCA3’.”
He added: “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.”
The researchers have developed a clinical test for PALB2, which will become part of their NHS service. Clinical testing for PALB2 will soon also be available in other diagnostic laboratories worldwide.
