PALB2 gene dramatically increases breast cancer risk

11 August 2014

New research has found that women carrying mutations in the PALB2 gene have a one in three chance of developing breast cancer by the age of seventy.

The PALB2 gene was first linked with breast cancer in 2007, and is known to interact with both BRCA2 and BRCA1 genes; with all three playing an important role in the repair of damaged DNA. The new research gives a more solid understanding of the breast cancer risk associated with loss-of-function mutations in the PALB2 gene. 

The research published in the New England Journal of Medicine consisted of data from multiple centres worldwide led by researchers from Cambridge, collaborating through the international PALB2 Interest Group. Data was analysed from 154 families without BRCA1/2 mutations, in which 362 family members had loss-of-function mutations in the PALB2 gene. 

The risk of breast cancer for PALB2 carriers was highly dependent on family history, with carriers being at a higher risk if they had relatives affected by breast cancer. The researchers highlighted that additional studies in families with newly identified PALB2 mutations are needed to obtain precise estimates of mutation carrier frequency in the population. Only a very small proportion of women worldwide carry the mutation.  

The PALB2 mutation associated cancer risk may justify addition to genetic testing for BRCA1/2 mutations, especially as it is a higher risk than other well-known loss-of-function mutations, such as in the CHEK2 gene, according to the researchers. A clinical test for PALB2 has been developed and is in use at the Cambridge University NHS Hospitals Trust.

Further, PARP inhibitors that are currently being trialled in BRCA1/2 related breast cancers may also work with PALB2-related breast cancer, as there is evidence that cells carrying PALB2 mutation are sensitive to them. 

Dr Antonis Antoniou from the Centre for Cancer Genetic Epidemiology at the University of Cambridge said: “Knowing the key genes that significantly increase cancer risk and having precise cancer risk estimates ultimately could help assess the breast cancer risk for each woman and allow better targeting or surveillance”.

This latest finding is relevant to previous work by the PHG Foundation, which suggests that the incorporation of selected genetic information in risk calculations could ultimately make cancer screening programmes more effective. This is a form of personalised prevention enabled by advances in genomics.

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