BRCA germline mutations in Jewish patients with pancreatic adenocarcinoma Journal Article


Authors: Ferrone, C. R.; Levine, D. A.; Tang, L. H.; Allen, P. J.; Jarnagin, W.; Brennan, M. F.; Offit, K.; Robson, M. E.
Article Title: BRCA germline mutations in Jewish patients with pancreatic adenocarcinoma
Abstract: Purpose The prognostic significance of germline BRCA1 and BRCA2 mutations in Jewish patients with pancreatic adenocarcinoma (PAC) is unknown. Our objective was to define the prevalence of BRCA1 and BRCA2 in an unselected group of Jewish patients and to compare the clinical characteristics and overall survival (OS) of patients with resected BRCA mutation-associated PAC to PAC patients without mutations. Patients and Methods Jewish patients with PAC resected between January 1986 and January 2004 were identified. DNA was extracted from the archived material, anonymized, and genotyped for founder mutations in BRCA1 (185delAG, 5382insC) and BRCA2 (6174delT). Standard two-sided statistical tests were utilized. Results Of the 187 Jewish patients who underwent resection for PAC, tissue was available for 145 patients. Eight subjects (5.5%) had a BRCA founder mutation (two with BRCA1 [1.3%], six with BRCA2 [4.1%]). The BRCA2 founder mutation was identified in 4.1% of patients with pancreatic adenocarcinoma compared with only 1.1% of cancer-free Washington, DC,-area controls (4.1% v 1.1%; P = .007; odds ratio, 3.85; 95% CI, 2.1 to 10.8). Patients with and without BRCA1 or BRCA2 mutations did not differ in age (mean, 66 v 73 years; P = .6) or other clinicopathologic features. OS was not significantly different (median, 6 v 16 months; P = .35). A previous cancer was reported by 24% (35 of 145) of patients with the most common sites being breast cancer (9 of 35; 74%) and prostate cancer (8 of 35; 23%). Conclusion Founder mutations for BRCA1 and BRCA2 were identified in 5.5% of Ashkenazi patients operated on for PAC. BRCA2 mutations were more prevalent than documented by population studies. Consistent with previous reports, BRCA2 mutations are associated with an increased risk of PAC. © 2008 by American Society of Clinical Oncology.
Keywords: adult; cancer survival; controlled study; human tissue; aged; aged, 80 and over; middle aged; gene mutation; major clinical study; mutation; clinical feature; cancer localization; pancreatic neoplasms; adenocarcinoma; breast cancer; genotype; brca1 protein; brca2 protein; prostate cancer; genes, brca1; genes, brca2; pancreas adenocarcinoma; dna extraction; founder effect; jews
Journal Title: Journal of Clinical Oncology
Volume: 27
Issue: 3
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2009-01-20
Start Page: 433
End Page: 438
Language: English
DOI: 10.1200/jco.2008.18.5546
PUBMED: 19064968
PROVIDER: scopus
PMCID: PMC3657622
DOI/URL:
Notes: --- - "Cited By (since 1996): 10" - "Export Date: 30 November 2010" - "CODEN: JCOND" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Cristina Ferrone
    32 Ferrone
  2. Murray F Brennan
    759 Brennan
  3. Kenneth Offit
    509 Offit
  4. Mark E Robson
    365 Robson
  5. Douglas A Levine
    356 Levine
  6. Peter Allen
    436 Allen
  7. William R Jarnagin
    583 Jarnagin
  8. Laura Hong Tang
    320 Tang