title: Prevalence of BRCA2 and CDKN2a mutations in German familial pancreatic cancer families.
abstract: Previous small scale studies reported that deleterious BRCA2 and CDKN2a germline mutations contribute to a subset of families with inherited pancreatic cancer. As the prevalence of those mutations in the setting of familial pancreatic cancer is still not well defined for the German population, we evaluated the presence of BRCA2 and CDKN2a germline mutations in a large cohort of familial pancreatic cancer (FPC) families from the German National Case Collection for Familial Pancreatic Cancer (FaPaCa). Fifty-six FPC families with at least two-first-degree relatives with confirmed pancreatic cancer that did not fulfill the criteria of other tumor predisposition syndromes, were analyzed for BRCA2 and CDKN2a germline mutations by DHPLC and/or direct sequencing. No deleterious CDKN2a mutations were identified in our families suggesting that CDKN2a mutations are unlikely to predispose PC in FPC families without melanoma. No deleterious BRCA2 mutations, but 6 unclassified variants, were detected in our FPC collection. Combining the prevalence of deleterious BRCA2 germline mutations from our previous separate study with the data from this study we were able to much more accurately estimate the BRCA2 carrier frequency for FPC families in the German population. A total of two mutations and 6 unclassified variants (mutation range: 2.8-11.4%) were thus identified in 70 German FPC families, indicating that the prevalence of BRCA2 mutations in the German FPC population is less frequent than previously reported.
authors.affiliation: Department of Visceral-, Thoracic and Vascular Surgery, Philipps-University Marburg, Baldingerstrasse, 35043, Marburg, Germany. slater@med.uni-marburg.de
authors.forename: Emily P
authors.initials: EP
authors.lastname: Slater
authors.forename: Peter
authors.initials: P
authors.lastname: Langer
authors.forename: Volker
authors.initials: V
authors.lastname: Fendrich
authors.forename: Nils
authors.initials: N
authors.lastname: Habbe
authors.forename: Brunhilde
authors.initials: B
authors.lastname: Chaloupka
authors.forename: Elvira
authors.initials: E
authors.lastname: Matthäi
authors.forename: Mercedes
authors.initials: M
authors.lastname: Sina
authors.forename: Stephan A
authors.initials: SA
authors.lastname: Hahn
authors.forename: Detlef K
authors.initials: DK
authors.lastname: Bartsch
mesh_terms: D002851:Chromatography, High Pressure Liquid; D004252:DNA Mutational Analysis; D005260:Female; D024522:Genes, BRCA2; D019942:Genes, p16; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D005858:Germany; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000453:epidemiology / Q000235:genetics*; D010375:Pedigree; D015995:Prevalence; D012042:Registries