title: Absence of germline BRCA1 mutations in familial pancreatic cancer patients.
abstract: Recent studies have suggested that germ line mutations in the BRCA1 gene may confer an increased risk of developing pancreatic cancer. To determine if BRCA1 mutations explain a significant proportion of familial pancreatic cancer, we sequenced the BRCA1 gene in a large series of well-characterized patients with familial pancreatic cancer and we evaluated the pathology of breast neoplasms that developed in relatives of pancreatic cancer patients. The BRCA1 gene was fully sequenced in 66 pancreatic cancer patients enrolled in the National Familial Pancreas Tumor Registry who had at least two additional relatives with pancreatic cancer. None of the 66 (0/66: 97.5% one-side CI 0-0.054%) familial pancreatic cancer patients were found to have a deleterious mutation in the BRCA1 gene. While patients were not selected based upon their family history of breast and ovarian cancer, over half of the patients whose samples were sequenced reported a family history of breast and/or ovarian cancer. Our findings suggest that mutations in the BRCA1 gene are not highly, or even moderately, prevalent in families with a clustering of pancreatic cancer, including pancreatic cancer families who report a family history of breast and/or ovarian cancer.
authors.affiliation: Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Axilbund
authors.forename: Pedram
authors.initials: P
authors.lastname: Argani
authors.forename: Mihoko
authors.initials: M
authors.lastname: Kamiyama
authors.forename: Emily
authors.initials: E
authors.lastname: Palmisano
authors.forename: Marian
authors.initials: M
authors.lastname: Raben
authors.forename: Michael
authors.initials: M
authors.lastname: Borges
authors.forename: Kieran A
authors.initials: KA
authors.lastname: Brune
authors.forename: Michael
authors.initials: M
authors.lastname: Goggins
authors.forename: Ralph H
authors.initials: RH
authors.lastname: Hruban
authors.forename: Alison P
authors.initials: AP
authors.lastname: Klein
mesh_terms: D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D005190:Family; D005260:Female; D019398:Genes, BRCA1; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D015995:Prevalence; D012042:Registries; D017422:Sequence Analysis, DNA; D014481:United States / Q000453:epidemiology
chemical_list: D004273:DNA, Neoplasm