Genetics and Pancreatic Cancer

Several specific genetic mutations and hereditary syndromes increase the risk of pancreatic cancer. Key gene mutations associated with higher pancreatic cancer risk include: 

  • BRCA2 and BRCA1: Mutations in BRCA2 are linked to a 3–10 fold increased risk, and BRCA1 mutations also raise risk, though to a lesser degree. 1, 2, 3

  • PALB2: This gene interacts with BRCA2, and mutations here raise risk for pancreatic cancer and familial breast cancer. 1, 3

  • ATM: Mutations in the ATM gene, responsible for ataxia-telangiectasia, contribute to an increased risk of pancreatic cancer. 1, 2, 3

  • CDKN2A (p16): Found in familial atypical multiple mole melanoma (FAMMM) syndrome, significantly raises risk. 1, 3, 4

  • STK11 (LKB1): Associated with Peutz-Jeghers syndrome, this mutation carries a particularly high risk for pancreatic cancer. 1, 3, 5

  • PRSS1: Seen in hereditary pancreatitis, this mutation brings a markedly increased lifetime risk. 1, 3

  • MLH1, MSH2, MSH6, PMS2: These mismatch repair (MMR) gene mutations are associated with Lynch syndrome (hereditary non-polyposis colorectal cancer), increasing the risk for several cancers, including pancreatic cancer. 1, 3, 5

Other genetic conditions and genes (such as PALB2, and rare alterations in TP53 seen in Li-Fraumeni syndrome) may also contribute to increased pancreatic cancer risk, particularly in families with a history of multiple cancers. 3, 5

 

Genetic testing is recommended for individuals with a significant family history or syndromic features to guide screening and risk-reduction strategies. 1, 3, 5

AB Health Solutions provides access to testing for hereditary syndromes that increase the risk of pancreatic cancer