Background: The genetic basis of susceptibility to prostate cancer (PRCA) remains elusive. Mutations in BRCA2 have been associated with increased prostate cancer risk and account for around 2% of young onset (<56 years) prostate cancer cases. PALB2 is a recently identified breast cancer susceptibility gene whose protein is closely associated with BRCA2 and is essential for BRCA2 anchorage to nuclear structures. This functional relationship made PALB2 a candidate PRCA susceptibility gene.
Methods: We sequenced PALB2 in probands from 95 PRCA families, 77 of which had two or more cases of early onset PRCA (age at diagnosis <55 years), and the remaining 18 had one case of early onset PRCA and five or more total cases of PRCA.
Results: Two previously unreported variants, K18R and V925L were identified, neither of which is in a known PALB2 functional domain and both of which are unlikely to be pathogenic. No truncating mutations were identified.
Conclusions: These results indicate that deleterious PALB2 mutations are unlikely to play a significant role in hereditary prostate cancer.