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Prevalence of BRCA1 and BRCA2 mutations in Ashkenazi Jewish families with breast and pancreatic cancer
Article first published online: 19 MAY 2011
Copyright © 2011 American Cancer Society
Volume 118, Issue 2, pages 493–499, 15 January 2012
How to Cite
Stadler, Z. K., Salo-Mullen, E., Patil, S. M., Pietanza, M. C., Vijai, J., Saloustros, E., Hansen, N. A. L., Kauff, N. D., Kurtz, R. C., Kelsen, D. P., Offit, K. and Robson, M. E. (2012), Prevalence of BRCA1 and BRCA2 mutations in Ashkenazi Jewish families with breast and pancreatic cancer. Cancer, 118: 493–499. doi: 10.1002/cncr.26191
- Issue published online: 5 JAN 2012
- Article first published online: 19 MAY 2011
- Manuscript Accepted: 24 MAR 2011
- Manuscript Revised: 16 MAR 2011
- Manuscript Received: 10 JAN 2011
- BRCA mutation;
- pancreatic cancer;
- breast cancer;
- Ashkenazi Jewish;
- mutation prevalence
Germline mutations in the BRCA2 cancer susceptibility gene are associated with an increased risk of pancreatic cancer (PC). Breast-pancreas cancer families with BRCA1 mutations have also been observed. The influence of a family history (FH) of PC on BRCA mutation prevalence in patients with breast cancer (BC) is unknown.
A clinical database review (2000-2009) identified 211 Ashkenazi Jewish (AJ) BC probands who 1) underwent BRCA1/2 mutation analysis by full gene sequencing or directed testing for Ashkenazi founder mutations (BRCA1: 185delAG and 5382insC; BRCA2: 6174delT) and 2) had a FH of PC in a first-, second-, or third-degree relative. For each proband, the pretest probability of identifying a BRCA1/2 mutation was estimated using the Myriad II model. The observed-to-expected (O:E) mutation prevalence was calculated for the entire group.
Of the 211 AJ BC probands with a FH of PC, 30 (14.2%) harbored a BRCA mutation. Fourteen (47%) of the mutations were in BRCA1 and 16 (53%) were in BRCA2. Patients diagnosed with BC at age ≤ 50 years were found to have a higher BRCA1/2 mutation prevalence than probands with BC who were diagnosed at age > 50 years (21.1% vs 6.9%; P = .003). In patients with a first-, second-, or third-degree relative with PC, mutation prevalences were 15.4%, 15.3%, and 8.6%, respectively (P = .58). In the overall group, the observed BRCA1/2 mutation prevalence was 14.2% versus an expected prevalence of 11.8% (O:E ratio, 1.21; P = .15).
BRCA1 and BRCA2 mutations are observed with nearly equal distribution in AJ breast-pancreas cancer families, suggesting that both genes are associated with PC risk. In this population, a FH of PC was found to have a limited effect on mutation prevalence. Cancer 2011;. © 2011 American Cancer Society.