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.

Familial Pancreatic Cancer

“…These centers include an FPC registry, which aids screening programs, with the aim of finding the cause of PDAC and developing better treatment options using the collected data [19]. Before the establishment of these centers, Lynch and colleagues [20,27] started a study with families who suffer from pancreatic cancer.…”

“…The first centers founded for screening of high-risk individuals were the National Familial Pancreas Tumor Registry (NFPTR) at Johns Hopkins University in 1994, the European Registry of Hereditary Pancreatitis and Familial Pancreas Cancer (EUROPAC) at Liverpool University in 1997, and the German National Case Collection for Familial Pancreatic Carcinoma (FaPaCa) at Philipps University Marburg in 1999 [19,27,74,75,76]. After this, more centers in Japan (Kyoto University, Japanese Familial Pancreatic Cancer Registry), USA (17 centers), Canada (Mount Sinai Hospital, Toronto, Familial Gastrointestinal Cancer Registry), Europe (Germany, Italy, Spain), and Australia (The Kinghorn Cancer Center, Australian Pancreatic Cancer Genome Initiative) have been established [19].…”

“…These screening programs collect data to generate more knowledge about origin, development, genetic background, tumor cell and stroma interaction, diagnosis, and therapy of pancreatic cancer [19,21,23]. They also screen for non-invasive precursor lesions, which can be further observed or resected to avoid the development of cancer and improve the survival of high-risk individuals [19].…”

“…Since the background of familial pancreatic cancer (FPC) is known, several screening programs are available for patients who have a higher risk of developing PDAC [19,20]. The International Cancer of the Pancreas Screening (CAPS) Consortium developed guidelines for screening and management of patients with higher risk or predisposition for pancreatic cancer [21].…”

“…They also screen for non-invasive precursor lesions, which can be further observed or resected to avoid the development of cancer and improve the survival of high-risk individuals [19]. Typical screening methods include magnetic resonance imaging (MRI) and endoscopic ultrasonography (EUS) [24].…”