Analysis of 96 additional patients with familial pancreatic cancer revealed three distinct protein-truncating mutations, thereby validating the role of PALB2 as a susceptibility gene for pancreatic cancer.
Our results indicate that hereditary PALB2 mutation represents clinically considerable genetic factor increasing PDAC susceptibility in our population and that analysis of PALB2 should be considered not only in PDAC patients with familial history of breast or pancreatic cancers but also in younger PDAC patients without family cancer history.
Recently, PALB2 was reported to be a new pancreatic cancer susceptibility gene as determined by exomic sequencing, as truncating PALB2 mutations were identified in 3 of 96 American patients with familial pancreatic cancer (FPC).
PALB2 heterozygotes were 4-fold more likely to have a male relative with breast cancer (P = 0.0003), 6-fold more likely to have a relative with pancreatic cancer (P = 0.002), and 1.3-fold more likely to have a relative with ovarian cancer (P = 0.18).
PALB2 is a breast and pancreas cancer susceptibility gene whose protein is closely associated with BRCA2 and is essential for BRCA2 anchorage to nuclear structures.