Surveillance of CDNK2A mutation carriers is relatively successful, detecting most PDACs at a resectable stage. The benefit of surveillance in families with FPC is less evident.

Familial pancreatic cancer (FPC) is a rare hereditary tumor syndrome. The 10-years experience of the national case collection for familial pancreatic cancer of Germany (FaPaCa) is reported. Since 1999 FaPaCa has collected families with at least two first-degree relatives with confirmed pancreatic cancer (PC), who did not fulfill the criteria of other hereditary tumor syndromes. Histopathological verification of tumor diagnoses, and genetic counseling were prerequisites for enrollment of families in FaPaCa. 94 of 452 evaluated families fulfilled the criteria for partaking in FaPaCa. PC represented the sole tumor entity in 38 (40%) families. In 56 families additional tumor types occurred, including breast cancer (n = 28), colon cancer (n = 20) and lung cancer (n = 11). In 70 (74%) families the pattern of inheritance was consistent with an autosomal dominant trait. Compared to the preceding generation, a younger age of onset was observed in the offspring of PC patients (median: 57 vs. 69 years), indicating anticipation. Mutation analyses of BRCA2, PALB2, CDKN2a, RNASEL, STK11, NOD2, CHEK2 and PALLD, revealed deleterious causative germline mutations of BRCA2 and PALB2 in 2 of 70 (3%) and 2 of 41 (4.9%) German FPC families, respectively. Prospective PC screening with EUS, MRI and MRCP detected precancerous lesions (IPMN, multifocal PanIN2/3) or carcinoma in 5.5% (4 of 72) to 12.5% (9 of 72) of individuals at risk, depending on histological verification. Appropriate inclusion of families at high risk for PC in registries, such as FaPaCa, provides a unique and excellent tool to gain clinical and genetic knowledge of FPC. Focused research projects can be conducted most efficiently, when data of different FPC registries are combined.

It appears safe to start screening for PDAC in IAR of non-CDKN2a FPC families at the age of 50 years. MRI-based screening supplemented by EUS at baseline and every 3rd year or when changes in MRI occur appears to be efficient.

Screening programs are recommended for individuals at risk (IAR) from families with familial pancreatic cancer (FPC). However, reliable imaging methods or biomarkers for early diagnosis of pancreatic ductal adenocarcinoma (PC) or its precursor lesions are still lacking. The ability of circulating microRNAs (miRNAs) to discriminate multifocal high-grade precursor lesions or PC from normal was examined. The presence of miRNA-21, -155, -196a, -196b and -210 was analyzed in the serum of transgenic KPC mice to test their ability to distinguish mice with different grades of pancreatic intraepithelial neoplasia (mPanIN1–3) or PC from control mice. Serum levels of miR-196a and -196b were significantly higher in mice with PanIN2/3 lesions (n = 10) or PC (n = 8) as compared to control mice (n = 10) or mice with PanIN1 lesions (n = 10; P = .01). In humans, miR-196a and -196b were also diagnostic. Patients with PC, sporadic (n = 9) or hereditary (n = 10), and IAR with multifocal PanIN2/3 lesions (n = 5) had significantly higher serum levels than patients with neuroendocrine pancreatic tumors (n = 10) or chronic pancreatitis (n = 10), IAR with PanIN1 or no PanIN lesions (n = 5), and healthy controls (n = 10). The combination of both miR-196a and -196b reached a sensitivity of 1 and specificity of 0.9 (area under the curve = 0.99) to diagnose PC or high-grade PanIN lesions. In addition, preoperative elevated serum levels of miR-196a and -196b in patients with PC or multifocal PanIN2/3 lesions dropped to normal after potential curative resection. The combination of miR-196a and -196b may be a promising biomarker test for the screening of IAR for FPC.