Originally published as JCO Early Release 10.1200/JCO.2008.18.5546 on December 8 2008

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BRCA Germline Mutations in Jewish Patients With Pancreatic Adenocarcinoma

Cristina R. Ferrone, Douglas A. Levine, Laura H. Tang, Peter J. Allen, William Jarnagin, Murray F. Brennan, Kenneth Offit, Mark E. Robson

From the Departments of Surgery, Pathology, and Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY

Corresponding author: Mark E. Robson, MD, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021; e-mail: robsonm{at}mskcc.org

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.

published online ahead of print at www.jco.org on December 8, 2008.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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