title: The prevalence of BRCA2 mutations in familial pancreatic cancer.
abstract: Mutations in the BRCA2 gene have been implicated in pancreatic cancer susceptibility through studies of high-risk breast and ovarian cancer families. To determine the contribution of mutations in BRCA2 to familial pancreatic cancer, we screened affected probands from 151 high-risk families identified through pancreatic cancer clinics for germ-line BRCA2 mutations. Of these families, 118 had two or more first- and second-degree relatives with pancreatic cancer, and an additional 33 had two or more affected second-degree relatives. The average age of onset for pancreatic cancer was 62.8 years. Five BRCA2 truncating mutations were identified, three in families with two or more first- and second-degree relatives with pancreatic cancer. Three of the families with mutations had a history of breast cancer but not ovarian cancer. Four of five families with mutations were identified through probands with early-onset (<55 years) pancreatic cancer. The results of this study were combined with those from a BRCA2 mutation study of 29 other families from the same Johns Hopkins University National Familial Pancreatic Tumor Registry to estimate the frequency of BRCA2 mutations. A total of 10 carriers from 180 families were identified, suggesting that BRCA2 mutations account for 6% of moderate and high-risk pancreatic cancer families.
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA. couch.fergus@mayo.edu
authors.forename: Fergus J
authors.initials: FJ
authors.lastname: Couch
authors.forename: Michele R
authors.initials: MR
authors.lastname: Johnson
authors.forename: Kari G
authors.initials: KG
authors.lastname: Rabe
authors.forename: Kieran
authors.initials: K
authors.lastname: Brune
authors.forename: Mariza
authors.initials: M
authors.lastname: de Andrade
authors.forename: Michael
authors.initials: M
authors.lastname: Goggins
authors.forename: Heidi
authors.initials: H
authors.lastname: Rothenmund
authors.forename: Steven
authors.initials: S
authors.lastname: Gallinger
authors.forename: Alison
authors.initials: A
authors.lastname: Klein
authors.forename: Gloria M
authors.initials: GM
authors.lastname: Petersen
authors.forename: Ralph H
authors.initials: RH
authors.lastname: Hruban
mesh_terms: D017668:Age of Onset; D002851:Chromatography, High Pressure Liquid; D005260:Female; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010190:Pancreatic Neoplasms / Q000235:genetics*; D016133:Polymerase Chain Reaction; D015995:Prevalence; D012042:Registries; D012307:Risk Factors