title: 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-rasmutations, similar to colorectal polyposis seen in the FAP patients. As with HBOC patients, a patient who is aBRCAmutation 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.
authors.affiliation: Hiroyuki Matsubayashi, Division of Endoscopy, Shizuoka Cancer Center, Shizuoka 411-8777, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Matsubayashi
authors.affiliation: Hiroyuki Matsubayashi, Division of Endoscopy, Shizuoka Cancer Center, Shizuoka 411-8777, Japan.
authors.forename: Kyoichi
authors.initials: K
authors.lastname: Takaori
authors.affiliation: Hiroyuki Matsubayashi, Division of Endoscopy, Shizuoka Cancer Center, Shizuoka 411-8777, Japan.
authors.forename: Chigusa
authors.initials: C
authors.lastname: Morizane
authors.affiliation: Hiroyuki Matsubayashi, Division of Endoscopy, Shizuoka Cancer Center, Shizuoka 411-8777, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Maguchi
authors.affiliation: Hiroyuki Matsubayashi, Division of Endoscopy, Shizuoka Cancer Center, Shizuoka 411-8777, Japan.
authors.forename: Masamichi
authors.initials: M
authors.lastname: Mizuma
authors.affiliation: Hiroyuki Matsubayashi, Division of Endoscopy, Shizuoka Cancer Center, Shizuoka 411-8777, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: Hiroyuki Matsubayashi, Division of Endoscopy, Shizuoka Cancer Center, Shizuoka 411-8777, Japan.
authors.forename: Keita
authors.initials: K
authors.lastname: Wada
authors.affiliation: Hiroyuki Matsubayashi, Division of Endoscopy, Shizuoka Cancer Center, Shizuoka 411-8777, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Hosoi
authors.affiliation: Hiroyuki Matsubayashi, Division of Endoscopy, Shizuoka Cancer Center, Shizuoka 411-8777, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Yachida
authors.affiliation: Hiroyuki Matsubayashi, Division of Endoscopy, Shizuoka Cancer Center, Shizuoka 411-8777, Japan.
authors.forename: Masami
authors.initials: M
authors.lastname: Suzuki
authors.affiliation: Hiroyuki Matsubayashi, Division of Endoscopy, Shizuoka Cancer Center, Shizuoka 411-8777, Japan.
authors.forename: Risa
authors.initials: R
authors.lastname: Usui
authors.affiliation: Hiroyuki Matsubayashi, Division of Endoscopy, Shizuoka Cancer Center, Shizuoka 411-8777, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Furukawa
authors.affiliation: Hiroyuki Matsubayashi, Division of Endoscopy, Shizuoka Cancer Center, Shizuoka 411-8777, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Furuse
authors.affiliation: Hiroyuki Matsubayashi, Division of Endoscopy, Shizuoka Cancer Center, Shizuoka 411-8777, Japan.
authors.forename: Takamitsu
authors.initials: T
authors.lastname: Sato
authors.affiliation: Hiroyuki Matsubayashi, Division of Endoscopy, Shizuoka Cancer Center, Shizuoka 411-8777, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Ueno
authors.affiliation: Hiroyuki Matsubayashi, Division of Endoscopy, Shizuoka Cancer Center, Shizuoka 411-8777, Japan.
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Kiyozumi
authors.affiliation: Hiroyuki Matsubayashi, Division of Endoscopy, Shizuoka Cancer Center, Shizuoka 411-8777, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Hijioka
authors.affiliation: Hiroyuki Matsubayashi, Division of Endoscopy, Shizuoka Cancer Center, Shizuoka 411-8777, Japan.
authors.forename: Nobumasa
authors.initials: N
authors.lastname: Mizuno
authors.affiliation: Hiroyuki Matsubayashi, Division of Endoscopy, Shizuoka Cancer Center, Shizuoka 411-8777, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Terashima
authors.affiliation: Hiroyuki Matsubayashi, Division of Endoscopy, Shizuoka Cancer Center, Shizuoka 411-8777, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Mizumoto
authors.affiliation: Hiroyuki Matsubayashi, Division of Endoscopy, Shizuoka Cancer Center, Shizuoka 411-8777, Japan.
authors.forename: Yuzo
authors.initials: Y
authors.lastname: Kodama
authors.affiliation: Hiroyuki Matsubayashi, Division of Endoscopy, Shizuoka Cancer Center, Shizuoka 411-8777, Japan.
authors.forename: Masako
authors.initials: M
authors.lastname: Torishima
authors.affiliation: Hiroyuki Matsubayashi, Division of Endoscopy, Shizuoka Cancer Center, Shizuoka 411-8777, Japan.
authors.forename: Takahisa
authors.initials: T
authors.lastname: Kawaguchi
authors.affiliation: Hiroyuki Matsubayashi, Division of Endoscopy, Shizuoka Cancer Center, Shizuoka 411-8777, Japan.
authors.forename: Reiko
authors.initials: R
authors.lastname: Ashida
authors.affiliation: Hiroyuki Matsubayashi, Division of Endoscopy, Shizuoka Cancer Center, Shizuoka 411-8777, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kitano
authors.affiliation: Hiroyuki Matsubayashi, Division of Endoscopy, Shizuoka Cancer Center, Shizuoka 411-8777, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Hanada
authors.affiliation: Hiroyuki Matsubayashi, Division of Endoscopy, Shizuoka Cancer Center, Shizuoka 411-8777, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Furukawa
authors.affiliation: Hiroyuki Matsubayashi, Division of Endoscopy, Shizuoka Cancer Center, Shizuoka 411-8777, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Kawabe
authors.affiliation: Hiroyuki Matsubayashi, Division of Endoscopy, Shizuoka Cancer Center, Shizuoka 411-8777, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Majima
authors.affiliation: Hiroyuki Matsubayashi, Division of Endoscopy, Shizuoka Cancer Center, Shizuoka 411-8777, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Shimosegawa
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D002277:Carcinoma / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics* / Q000628:therapy; D055088:Early Detection of Cancer / Q000379:methods*; D005060:Europe / Q000453:epidemiology; D020022:Genetic Predisposition to Disease; D006801:Humans; D015994:Incidence; D007564:Japan / Q000453:epidemiology; D009154:Mutation; D010180:Pancreatectomy; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics* / Q000628:therapy; D012307:Risk Factors; D014481:United States / Q000453:epidemiology
chemical_list: D000970:Antineoplastic Agents; D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human
keywords: familial pancreatic cancer; genetic; high risk; registry; surveillance