Increased prevalence of the BRCA2 polymorphic stop codon K3326X among individuals with familial pancreatic cancer

Sean T. Martin, Hiroyuki Matsubayashi, Carmelle D. Rogers, Juliet Philips, Fergus J. Couch, Kieran Brune, Charles J. Yeo, Scott E. Kern, Ralph H. Hruban, Michael Goggins

Research output: Contribution to journalArticlepeer-review

65 Scopus citations


Germline BRCA2 mutations predispose to the development of pancreatic cancer. A polymorphic stop codon in the coding region of BRCA2 (K3326X) has been described, and although an initial epidemiological study suggested it was not disease causing, subsequent studies have been inconclusive. To investigate the biological significance of the K3326X polymorphism, we determined its prevalence in patients with sporadic and familial pancreatic cancer. Using a case-control design, we studied 250 patients with resected sporadic pancreatic adenocarcinomas, 144 patients with familial pancreatic adenocarcinoma, 115 spouses of patients with pancreatic cancer, and a disease control group of 135 patients without a personal history of cancer who had undergone cholecystectomy for non-neoplastic disease. The K3326X polymorphism was detected using heteroduplex analysis and DNA sequencing. The BRCA2 K3326X polymorphism was significantly more prevalent in individuals with familial pancreatic cancer: 8/144 (5.6%) vs 3/250 controls (1.2%) (odds ratio, 4.84; 95% CI, 1.27-18.55, P < 0.01). One K3326X carrier with familial pancreatic cancer carried an alteration (IVS 16-2A > G) suspected to be deleterious. Excluding this case did not alter the significance of the association (OR: 4.24, P < 0.01). In contrast, there was no difference in prevalence among individuals with sporadic pancreatic cancer - 7/250 (OR: 2.37, 95% CI: 0.61-9.27). The increased prevalence of the BRCA2 K3326X polymorphism in patients with familial pancreatic cancer suggests that this polymorphism is deleterious and contributes to pancreatic cancer risk.

Original languageEnglish (US)
Pages (from-to)3652-3656
Number of pages5
Issue number22
StatePublished - May 19 2005


  • BRCA2
  • Familial pancreatic cancer
  • K3326X

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research


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