Family History and Genetic Mutations
Not all pancreatic cancer risk comes from what you eat or how you live. Genetics plays a substantial and sometimes dominant role. About 10% of pancreatic cancer cases are related to inherited mutations.
If a first-degree relative, that is, a parent, sibling, or child, is diagnosed with pancreatic cancer, you may have an increased risk of developing the disease. That family member is strongly recommended to get genetic testing for inherited mutations. The risk compounds with the number of affected relatives. The risk increases if more family members are affected, and also increases if there is a history of familial breast, ovarian, or colon cancer, familial melanoma, or hereditary pancreatitis.
The BRCA2 Gene
The gene most closely associated with inherited pancreatic cancer risk is BRCA2, a tumor suppressor gene best known for its role in breast and ovarian cancer. It is estimated that about 2 to 8% of pancreatic cancer patients, regardless of family history, carry a BRCA2 mutation. That figure rises to 6 to 16% for patients with a close family member with pancreatic cancer, and up to 17% in families with three or more pancreatic cancer cases. The risk of developing pancreatic cancer is about 2 to 6 times higher in BRCA2 mutation carriers compared to the general population.
An inherited mutation in the BRCA2 gene increases the risk of pancreatic cancer, and individuals of Jewish descent are more prone to this mutation.
Other High-Risk Genetic Variants
BRCA2 is not the only gene of concern. About 5 to 10% of pancreatic cancers occur due to high-risk, disease-causing changes in hereditary cancer genes, which include BRCA2, BRCA1, ATM, PALB2, CDKN2A, and DNA mismatch repair genes.
Hereditary syndromes that can cause pancreatic cancer include hereditary breast and ovarian cancer syndrome (caused by BRCA1 or BRCA2 mutations), hereditary breast cancer (caused by PALB2 mutations), ataxia telangiectasia (ATM gene), familial atypical multiple mole melanoma syndrome (CDKN2A gene), hereditary pancreatitis (PRSS1 gene), Lynch syndrome (MLH1 or MSH2 genes), and Peutz-Jeghers syndrome (STK11 gene).
Anyone with a family history involving two or more of these cancers, or with multiple relatives affected by pancreatic cancer, should speak with a genetic counselor. The National Familial Pancreas Tumor Registry at Johns Hopkins is one of the world’s largest resources for families navigating inherited pancreatic cancer risk.
Age, Sex, and Race: Non-Modifiable Demographic Factors
Most cases of pancreatic cancer develop between the ages of 60 and 80 years. According to U.S. statistics, the incidence is most pronounced in individuals aged 70 and older, with a median age at diagnosis of 71 years.
