Published online Feb 14, 2017. doi: 10.3748/wjg.v23.i6.935
Peer-review started: August 10, 2016
First decision: September 5, 2016
Revised: September 7, 2016
Accepted: January 18, 2017
Article in press: January 18, 2017
Published online: February 14, 2017
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.
Core tip: The incidence of pancreatic cancer increases with the number of family members with pancreatic cancer (PC). Familial pancreatic cancer (FPC) is defined as at least two first-degree relatives with PC that does not meet the criteria of other hereditary cancer syndromes. FPC has some epidemiological, pathological, and therapeutic characteristics. Since the 1990s, FPC registries have been established for use in studies to follow up high-risk individuals with family history of PC and hereditary cancer syndromes. Japan initiated a nationwide FPC registry in 2014, and several projects are expected at both the clinical and basic levels.