Familial pancreatic cancer: Concept, management and issues

Abstract

Familial pancreatic cancer (FPC) is broadly defined as two first-degree-relatives with pancreatic cancer (PC) and accounts for 4%-10% of PC. Several genetic syndromes, including Peutz-Jeghers syndrome, hereditary pancreatitis, hereditary breast-ovarian cancer syndrome (HBOC), Lynch syndrome, and familial adenomatous polyposis (FAP), also have increased risks of PC, but the narrowest definition of FPC excludes these known syndromes. When compared with other familial tumors, proven genetic alterations are limited to a small proportion (< 20%) and the familial aggregation is usually modest. However, an ethnic deviation (Ashkenazi Jewish > Caucasian) and a younger onset are common also in FPC. In European countries, "anticipation" is reported in FPC families, as with other hereditary syndromes; a trend toward younger age and worse prognosis is recognized in the late years. The resected pancreases of FPC kindred often show multiple pancreatic intraepithelial neoplasia (PanIN) foci, with various K-ras mutations, similar to colorectal polyposis seen in the FAP patients. As with HBOC patients, a patient who is a BRCA mutation carrier with unresectable pancreatic cancer (accounting for 0%-19% of FPC patients) demonstrated better outcome following platinum and Poly (ADP-ribose) polymerase inhibitor treatment. Western countries have established FPC registries since the 1990s and several surveillance projects for high-risk individuals are now ongoing to detect early PCs. Improvement in lifestyle habits, including non-smoking, is recommended for individuals at risk. In Japan, the FPC study group was initiated in 2013 and the Japanese FPC registry was established in 2014 by the Japan Pancreas Society.

Keywords: familial pancreatic cancer; genetic; high risk; registry; surveillance.

Figure 1

Worldwide mapping of the (familial) pancreatic cancer registries and genetic research institutions (1-24). 1: Memorial Sloan-Kettering Cancer Center, Familial Pancreatic Cancer Family Registry; 2: Johns Hopkins University, National Familial Pancreas Tumor Registry; 3: Indiana University, Familial Pancreatic Cancer Registry; 4: NorthShore University, Pancreatic Cancer Family Registry; 5: Northwestern University, Pancreatic Cancer Family Registry; 6: University of Nebraska Medical Center and Creighton University, Pancreatic Cancer Family Registry; 7: Huntsman Cancer Institute and University of Utah, Familial Pancreatic Cancer Registry; 8: University of Washington, Familial Pancreatic Cancer Registry; 9: Columbia University, Pancreatic Cancer Registry; 10: Thomas Jefferson University, Jefferson Pancreas Tumor Registry; 11: University of Oklahoma, National Pancreatic Cancer Registry; 12: Oregon Health & Science University, Oregon Pancreas Tumor Registry; 13: Dana-Farber Cancer Institute, Pancreatic Cancer Genes Study; 14: University of Pittsburgh, Pancreatic Adenocarcinoma Gene-Environment Risk Study and Registry; 15: Karmanos Cancer Center and Wayne State University, Pancreatic Cancer Genetic Study; 16: Mayo Clinic, Pancreatic Cancer Genetic Study; 17: University of Texas and MD Anderson Cancer Center, Pancreatic Cancer Genetic Study; 18: Mount Sinai Hospital, Toronto, Familial Gastrointestinal Cancer Registry; 19: Philipps University of Marburg, German National Case Collection Familial Pancreatic Cancer; 20: University of Liverpool, European Registry of Hereditary Pancreatitis and Familial Pancreatic Cancer; 21: National Registry for Familial Pancreatic Cancer in Italy; 22: Ramon y Cajal University Hospital, Madrid, Spanish Registry of Hereditary Pancreatic Cancer; 23: The Kinghorn Cancer Center, Australian Pancreatic Cancer Genome Initiative; 24: Kyoto University, Japanese Familial Pancreatic Cancer Registry.