published in the New England Journal of Medicine, indicate 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.
PALB2 is known to interact with both BRCA1 and BRCA2, with all three
genes playing an important role in repairing damaged DNA. PALB2 was first
linked with breast cancer in 2007 (see BioNews 390) but the associated risk of developing the
disease had not yet been established.
Dr Marc Tischkowitz from 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 is that if more existed we would have found them by now. PALB2 is a
potential candidate to be "BRCA3"'.
The PALB2 Interest Group, an international team
of researchers, analysed data from 154 families without BRCA1 or BRCA2 mutations, which
included 362 people with PALB2 gene mutations. The scientists found that for people carrying a PALB2 mutation the risk
of developing breast cancer was 35 percent, but could be even greater if there was also a strong family history of breast cancer.
Additionally, the researchers found that women with PALB2 mutations who
were born more recently tended to be at a higher lifetime risk of developing breast cancer
than those born earlier.
A similar phenomenon has been observed in BRCA mutation carriers and the
reasons for it are unclear. The scientists speculate that factors such as later
age at first childbirth, smaller families and earlier cancer diagnosis may play
Reassuringly, only a very small proportion of women worldwide carry PALB2
mutations. Study co-author Professor
William Foulkes, from McGill University in Montreal, Canada, told CBS News that
roughly one in a thousand women are thought to be carriers. Further studies are
required to obtain a more precise figure.
Dr Tischkowitz said: '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