title: BRCA1 and BRCA2 germline mutations are frequently demonstrated in both high-risk pancreatic cancer screening and pancreatic cancer cohorts.
abstract: BACKGROUND
  Approximately 10% of pancreatic ductal adenocarcinoma (PDAC) is due to a genetic predisposition, including the breast and ovarian cancer syndrome germline mutations BRCA1 and BRCA2. Knowledge of specific genetic mutations predisposing to PDAC may enable risk stratification, early detection, and the development of effective screening and surveillance programs. In the current study, the authors attempted to determine the diagnostic yield of testing for BRCA1/2 germline mutations in a PDAC screening cohort and a PDAC cohort referred for genetic testing.
  
  
  METHODS
  Patients in a high-risk PDAC prevention and genetics program or those with a personal history of PDAC who were referred for genetic evaluation underwent testing for BRCA1/2 germline mutations. Clinical BRCA1/2 genetic testing included testing for the 3 Ashkenazi Jewish founder mutations or BRCA1/2 comprehensive testing.
  
  
  RESULTS
  A total of 37 patients without PDAC underwent BRCA1/2 testing at the study institution. Genetic testing identified 7 patients who were BRCA1/2 carriers for a yield of 18.9%. Six patients carried Ashkenazi Jewish founder mutations (3 with BRCA1 and 3 with BRCA2), and 1 patient was found to have a BRCA2 mutation on comprehensive testing. Thirty-two patients with PDAC underwent BRCA1/2 genetic testing. Five patients had Ashkenazi Jewish founder mutations (2 with BRCA1 and 3 with BRCA2), and 2 patients were found to have BRCA2 mutations on comprehensive testing. The diagnostic yield was 7 of 32 patients (21.9%).
  
  
  CONCLUSIONS
  BRCA1/2 testing is useful in PDAC risk stratification and alters risk assignment and screening recommendations for mutation-positive patients and their families. Clinical BRCA1/2 testing should be considered in patients of Ashkenazi Jewish descent with a personal history or family history of PDAC, even in the absence of a family history of breast and ovarian cancer.
authors.affiliation: Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Aimee L
authors.initials: AL
authors.lastname: Lucas
authors.forename: Laura E
authors.initials: LE
authors.lastname: Frado
authors.forename: Caroline
authors.initials: C
authors.lastname: Hwang
authors.forename: Sheila
authors.initials: S
authors.lastname: Kumar
authors.forename: Lauren G
authors.initials: LG
authors.lastname: Khanna
authors.forename: Elana J
authors.initials: EJ
authors.lastname: Levinson
authors.forename: John A
authors.initials: JA
authors.lastname: Chabot
authors.forename: Wendy K
authors.initials: WK
authors.lastname: Chung
authors.forename: Harold
authors.initials: H
authors.lastname: Frucht
mesh_terms: D000328:Adult; D000368:Aged; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D021441:Carcinoma, Pancreatic Ductal / Q000175:diagnosis / Q000235:genetics* / Q000517:prevention & control; D015331:Cohort Studies; D055088:Early Detection of Cancer; D005260:Female; D018703:Founder Effect; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D018095:Germ-Line Mutation; D006801:Humans; D007585:Jews / Q000235:genetics; D008297:Male; D008403:Mass Screening / Q000379:methods; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000517:prevention & control; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human
keywords: BRCA1 gene; BRCA2 gene; diagnosis; genetic testing; pancreatic cancer; pancreatic cancer screening; pancreatic neoplasms
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