title: German national case collection for familial pancreatic cancer (FaPaCa): ten years experience.
abstract: 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.
authors.affiliation: Department of Visceral, Thoracic and Vascular Surgery, Philipps University Marburg, Baldingerstrasse, 35043 Marburg, Germany.
authors.forename: Ralph
authors.initials: R
authors.lastname: Schneider
authors.forename: Emily P
authors.initials: EP
authors.lastname: Slater
authors.forename: Mercede
authors.initials: M
authors.lastname: Sina
authors.forename: Nils
authors.initials: N
authors.lastname: Habbe
authors.forename: Volker
authors.initials: V
authors.lastname: Fendrich
authors.forename: Elvira
authors.initials: E
authors.lastname: Matthäi
authors.forename: Peter
authors.initials: P
authors.lastname: Langer
authors.forename: Detlef K
authors.initials: DK
authors.lastname: Bartsch
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000076164:Fanconi Anemia Complementation Group N Protein; D005260:Female; D024522:Genes, BRCA2; D005858:Germany; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: D000076164:Fanconi Anemia Complementation Group N Protein; D009687:Nuclear Proteins; C512790:PALB2 protein, human; D025521:Tumor Suppressor Proteins