Biomedical
Current status of inherited pancreatic cancer
Peer Reviewed
Abstract
Background It is estimated that about 10% of pancreatic cancer cases have a genetic background. People with a familial predisposition to pancreatic cancer can be divided into 2 groups. The first is termed hereditary pancreatic cancer, which occurs in individuals with a known hereditary cancer syndrome caused by germline single gene mutations (e.g.,BRCA1/2,CDKN2A). The second is considered as familial pancreatic cancer, which is associated with several genetic factors responsible for the more common development of pancreatic cancer in certain families, but the precise single gene mutation has not been found. Aim This review summarizes the current state of knowledge regarding the risk of pancreatic cancer development in hereditary pancreatic cancer and familial pancreatic cancer patients. Furthermore, it gathers the latest recommendations from the three major organizations dealing with the prevention of pancreatic cancer in high-risk groups and explores recent guidelines of scientific societies on screening for pancreatic cancers in individuals at risk for hereditary or familial pancreatic cancer. Conclusions In order to improve patients’ outcomes, authors of current guidelines recommend early and intensive screening in patients with pancreatic cancer resulting from genetic background. The screening should be performed in excellence centers. The scope, extent and cost-effectiveness of such interventions requires further studies.
Key Questions and Answers
1. What is the difference between hereditary pancreatic cancer and familial pancreatic cancer?
- Hereditary pancreatic cancer occurs due to known genetic mutations (e.g., BRCA1/2, CDKN2A), while familial pancreatic cancer involves multiple family members with pancreatic cancer but lacks a specific gene mutation.
2. What is the purpose of genetic testing for hereditary pancreatic cancer?
- Genetic testing helps identify individuals with mutations linked to hereditary cancer syndromes and assists in early detection, risk assessment, and the planning of preventive measures like screening and surgery.
3. How does the heritability of pancreatic cancer compare to earlier estimates?
- Recent data suggest that the heritability of pancreatic cancer could be more than twice as high as previously thought, with an estimate of 21.2% compared to earlier estimates of 10%.
4. What role do guidelines play in the management of hereditary pancreatic cancer?
- Current guidelines recommend early, intensive screening and genetic counseling for individuals with hereditary pancreatic cancer to improve patient outcomes and reduce the risk of late-stage diagnoses.
5. What are the main genetic syndromes associated with hereditary pancreatic cancer?
- Genetic syndromes like HBOC (BRCA1/2 mutations), FAMMM (CDKN2A mutations), PJS (STK11 mutations), and Lynch syndrome (MLH1, MSH2 mutations) are linked to an increased risk of hereditary pancreatic cancer.
6. How does BRCA1/2 mutation affect the risk of pancreatic cancer?
- BRCA1/2 mutations significantly increase the risk of pancreatic cancer, with a notably higher risk in women over 50. Screening for BRCA mutations in breast cancer patients can help detect pancreatic cancer earlier.
7. What is the relationship between familial melanoma and pancreatic cancer?
- In families with a history of familial melanoma, the presence of pancreatic cancer is a strong predictor of a pathogenic CDKN2A mutation, which significantly increases the risk of pancreatic cancer in affected individuals.
