Early Detection of Pancreatic Cancer

Sushil Kumar Garg; Suresh T. Chari


Curr Opin Gastroenterol. 2020;36(5):456-461. 

In This Article

Inherited Predisposition to Pancreatic Cancer

An inherited predisposition to pancreatic cancer can be categorized into three groups-familial pancreatic cancers (FPCs), hereditary tumor predisposition syndromes associated with germline mutation in CDKN2A, TP53, MLH1, BRCA2, ATM, and BRCA1, and genetic syndromes associated with chronic inflammation of the pancreas.[11] FPC is defined as families with two or more first-degree relatives affected by exocrine pancreatic cancer who do not meet the criteria for any other inherited tumor syndrome with increased risks of pancreatic cancer.[12] Patients with a family history of pancreatic cancer are considered high risk for the future development of pancreatic cancer, and future risk increases by the number of first-degree relatives affected (32 fold in kindred's with three first-degree relatives).[13] Patients with a family history of pancreatic cancer tend to develop pancreatic cancer at a relatively younger age.[14] Smoking is a very strong risk in patients with FPC, with about three times increased in the development of pancreatic cancer over the inherited risk.[15] FPC patients make up to 7% of total pancreatic cancer patients.[16]

Another risk factor for the development of pancreatic cancer is hereditary pancreatic cancer syndromes – like Peutz – Jeghers syndrome, hereditary breast–ovarian cancer syndrome, Lynch syndrome 2, familial atypical multiple mole melanoma, and Li–Fraumeni syndrome.[17] These syndromes occur as a consequence of a known germline pathogenic mutation, and they represent about 3% of all pancreatic cancer cases.

The third setting for the inherited risk of pancreatic cancer includes hereditary pancreatitis and cystic fibrosis (CF). Hereditary pancreatitis is an autosomal dominant disease caused by germline mutations of the cationic trypsinogen gene PRSS1 with a lifetime risk of 40%.[18] CF is caused by mutations in the CF transmembrane regulator gene with five times increased risk of pancreatic cancer.[18]