New breast cancer risk gene identified

UK scientists have identified a gene which, when mutated, doubles the risk of breast cancer developing in women who inherit a single copy. A faulty copy of the PALB2 gene is linked to an increased lifetime risk of the disease, from around one in nine to one in five. In a separate study, the team has also shown that inheriting two copies of the mutated gene causes a rare subtype of the genetic condition Fanconi anaemia. The scientists, based at the Institute of Cancer Research (ICR), published their findings in the journal Nature Genetics.

Most cases of breast cancer are not inherited, but around 5-10 per cent are due to a mutation in genes such as BRCA1 or BRCA2. Whilst most women have a 13 per cent chance of developing the disease in their lifetime, those with BRCA1 or BRCA2 mutations can face up to an 85 per cent chance. Both BRCA1 and BRCA2 make proteins responsible for repairing DNA damage. Researchers have long suspected that there are many other gene variants, which - although they are not linked to clearly inherited forms of breast cancer - can increase a person's risk of the disease. The ICR team has already identified three such genes, called CHEK2, ATM and BRIP1.

In the latest breast cancer study, the researchers looked at the PALB2 gene in 923 affected women who had a family history of the disease, but who did not carry BRCA1 or BRCA2 gene mutations. They also studied 1084 healthy women for comparison. Professor Nazneen Rahman, who lead both studies, said: 'We estimate that faults in the PALB2 gene contribute to around 100 cases of breast cancer in the UK each year'. She added that 'interestingly, one of the ten breast cancer cases we identified as being linked to PALB2 was a male breast cancer, which may mean faults in the PALB2 gene are associated with a higher risk of male breast cancer, but we need to investigate this link further before we know for sure'.

In the second study, the team looked at 82 children with Fanconi anaemia, who did not have mutations in any of the 11 previously identified genes associated with this condition. They discovered that seven of the children with a subtype of the disease - characterised by a high risk of childhood tumours - had two mutated copies of PALB2.

The PALB2 (PArtner and Localiser of BRCA2) gene also encodes a protein involved in DNA repair. This in turn increases their lifetime risk of developing cancer, since they are more likely to acquire mutations in crucial growth control genes. The two-fold increased risk conferred by PALB2 mutation is similar to the increased risk associated with the CHEK2, ATM and BRIP1 genes. Together, these genes are thought to account for around two per cent of all cases of breast cancer.

Professor John Toy, Cancer Research UK's medical director, said that 'the discovery of another gene that increases breast cancer risk albeit only for a small number of women is very important', adding 'gradually, we are beginning to learn more and more about the rogue genes that cause cancer in some families, and we hope one day to use this knowledge to help those at an increased risk of the disease'. He also said that identifying children with a unique type of Fanconi anaemia would help doctors looking after these particular patients in the future'.