Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 14, 2017; 23(6): 935-948
Published online Feb 14, 2017. doi: 10.3748/wjg.v23.i6.935
Familial pancreatic cancer: Concept, management and issues
Hiroyuki Matsubayashi, Kyoichi Takaori, Chigusa Morizane, Hiroyuki Maguchi, Masamichi Mizuma, Hideaki Takahashi, Keita Wada, Hiroko Hosoi, Shinichi Yachida, Masami Suzuki, Risa Usui, Toru Furukawa, Junji Furuse, Takamitsu Sato, Makoto Ueno, Yoshimi Kiyozumi, Susumu Hijioka, Nobumasa Mizuno, Takeshi Terashima, Masaki Mizumoto, Yuzo Kodama, Masako Torishima, Takahisa Kawaguchi, Reiko Ashida, Masayuki Kitano, Keiji Hanada, Masayuki Furukawa, Ken Kawabe, Yoshiyuki Majima, Toru Shimosegawa
Hiroyuki Matsubayashi, Division of Endoscopy, Shizuoka Cancer Center, Shizuoka 411-8777, Japan
Hiroyuki Matsubayashi, Yoshimi Kiyozumi, Clinic of Genetic Medicine, Shizuoka Cancer Center, Shizuoka 411-8777, Japan
Kyoichi Takaori, Department of Surgery, Kyoto University Graduate School of Medicine, Sakyo, Kyoto 606-8397, Japan
Chigusa Morizane, Hiroko Hosoi, Division of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Chuoku, Tokyo 104-0045, Japan
Hiroyuki Maguchi, Center for Gastroenterology, Teine-Keijinkai Hospital, Sapporo, Hokkaido 006-0811, Japan
Masamichi Mizuma, Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8574, Japan
Hideaki Takahashi, Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, Chiba 277-8577, Japan
Keita Wada, Department of Surgery, Teikyo University School of Medicine, Itabashi, Tokyo 173-8606, Japan
Shinichi Yachida, Masami Suzuki, Risa Usui, Division of Cancer Genomics, National Cancer Center Research Institute, Chuoku, Tokyo 104-0045, Japan
Toru Furukawa, Institute for Integrated Medical Sciences, Tokyo Women’s Medical University, Shinjuku, Tokyo 162-8666, Japan
Junji Furuse, Department of Internal Medicine, Kyorin University School of Medicine, Mitaka, Tokyo 181-8611, Japan
Takamitsu Sato, Division of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 236-0004, Japan
Makoto Ueno, Division of Hepatobiliary and Pancreatic Medical Oncology, Kanagawa Cancer Center, Yokohama, Kanagawa 241-8515, Japan
Susumu Hijioka, Nobumasa Mizuno, Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Aichi 464-8681, Japan
Takeshi Terashima, Department of Gastroenterology, Kanazawa University Graduate School of Medicine, Kanazawa, Ishikawa 920-8641, Japan
Masaki Mizumoto, Department of Surgery, Japan Bapist Hospital, Kyotoshi, Kyoto 606-8273, Japan
Yuzo Kodama, Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Sakyo, Kyoto 606-8397, Japan
Masako Torishima, Clinical Genetics Unit, Kyoto University Graduate School of Medicine, Sakyo, Kyoto 606-8397, Japan
Takahisa Kawaguchi, Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Sakyo, Kyoto 606-8397, Japan
Reiko Ashida, Osaka Medical Center for Cancer and Cardiovascular Diseases, Higashinari, Osaka 537-8511, Japan
Masayuki Kitano, Second Department of Internal Medicine, Wakayama Medical University, Wakayamashi, Wakayama 641-8509, Japan
Keiji Hanada, Department of Gastroenterology, Onomichi General Hospital, Onomichi, Hiroshima 722-8508, Japan
Masayuki Furukawa, Department of Gastroenterology, National Kyushu Cancer Center, Fukuokashi, Fukuoka 811-1395, Japan
Ken Kawabe, Department of Medicine and Bioregulatory Sciences, Kyushu University Graduate School of Medical Science, Fukuokashi, Fukuoka 812-8582, Japan
Yoshiyuki Majima, Pancreatic Cancer Action Network, Chiyoda, Tokyo 102-0071, Japan
Toru Shimosegawa, Department of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8574, Japan
Author contributions: All authors are core members of Japanese Familial Pancreatic Cancer Study Group; Matsubayashi H drafted and completed the manuscript, and all other authors reviewed and provided beneficial comments and discussions.
Conflict-of-interest statement: The authors have no conflict of interest relevant to this review.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Hiroyuki Matsubayashi, MD, PhD, Division of Endoscopy, Shizuoka Cancer Center, 1007, Shimonagakubo, Nagaizumi, Suntogun, Shizuoka 411-8777, Japan.
Telephone: +81-55-9895222 Fax: +81-55-9895692
Received: August 7, 2016
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
Processing time: 188 Days and 23.8 Hours

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, registry, high risk, genetic, surveillance

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.