title: BRCA2 germline mutations in familial pancreatic carcinoma.
abstract: BACKGROUND
  Although as many as 10% of pancreatic cancer cases may have an inherited component, familial pancreatic cancer has not been linked to defects in any specific gene. Some studies have shown that families with germline mutations in the breast cancer susceptibility gene BRCA2 have an increased risk of breast and ovarian cancers, as well as a modestly increased risk of pancreatic cancer. To study these relationships in more detail, we examined whether BRCA2 germline mutations are associated with familial pancreatic cancer.
  
  
  METHODS
  We identified 26 European families in which at least two first-degree relatives had a histologically confirmed diagnosis of pancreatic ductal adenocarcinoma. We sequenced genomic DNA isolated from peripheral blood lymphocytes obtained from participating family members to identify germline mutations in BRCA2.
  
  
  RESULTS
  Three (12%, exact 95% confidence interval [CI] = 2% to 30%) families carried germline frameshift mutations in the BRCA2 gene that are predicted to result in a truncated BRCA2 protein. Two additional families harbored mutations previously designated as unclassified variants of BRCA2. Thus, 19% (exact 95% CI = 7% to 39%) of the families in our study had either a frameshift mutation or an unclassified variant of BRCA2. None of the families in our study met the criteria for familial breast or ovarian cancer.
  
  
  CONCLUSIONS
  Our data support an important role for BRCA2 germline mutations in a subpopulation of families with familial pancreatic cancer. BRCA2 mutation analysis should be included in molecular genetic testing and counseling strategies in families with at least two first-degree relatives affected with ductal adenocarcinoma of the pancreas.
authors.affiliation: Department of Internal Medicine, Knappschaftskrankenhaus University of Bochum, Germany.
authors.forename: Stephan A
authors.initials: SA
authors.lastname: Hahn
authors.forename: Bill
authors.initials: B
authors.lastname: Greenhalf
authors.forename: Ian
authors.initials: I
authors.lastname: Ellis
authors.forename: Mercedes
authors.initials: M
authors.lastname: Sina-Frey
authors.forename: Harald
authors.initials: H
authors.lastname: Rieder
authors.forename: Birgit
authors.initials: B
authors.lastname: Korte
authors.forename: Berthold
authors.initials: B
authors.lastname: Gerdes
authors.forename: Ralf
authors.initials: R
authors.lastname: Kress
authors.forename: Andreas
authors.initials: A
authors.lastname: Ziegler
authors.forename: John A
authors.initials: JA
authors.lastname: Raeburn
authors.forename: Donata
authors.initials: D
authors.lastname: Campra
authors.forename: Robert
authors.initials: R
authors.lastname: Grützmann
authors.forename: Helga
authors.initials: H
authors.lastname: Rehder
authors.forename: Matthias
authors.initials: M
authors.lastname: Rothmund
authors.forename: Wolff
authors.initials: W
authors.lastname: Schmiegel
authors.forename: John P
authors.initials: JP
authors.lastname: Neoptolemos
authors.forename: Detlef K
authors.initials: DK
authors.lastname: Bartsch
mesh_terms: D000328:Adult; D000368:Aged; D004273:DNA, Neoplasm / Q000032:analysis; D005060:Europe; D005260:Female; D016368:Frameshift Mutation; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D005858:Germany; D006801:Humans; D008214:Lymphocytes; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D012042:Registries; D017422:Sequence Analysis, DNA
chemical_list: D004273:DNA, Neoplasm