Prevalence of BRCA1 and BRCA2 mutations in Ashkenazi Jewish families with breast and pancreatic cancer Journal Article
| Authors: | 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.; Robson, M. E. |
| Article Title: | Prevalence of BRCA1 and BRCA2 mutations in Ashkenazi Jewish families with breast and pancreatic cancer |
| Abstract: | BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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. © 2011 American Cancer Society. |
| Keywords: | adult; controlled study; aged; gene mutation; major clinical study; sequence analysis; gene deletion; cancer risk; pancreas cancer; cancer susceptibility; breast cancer; prevalence; genetic association; mutational analysis; brca1 protein; brca2 protein; data base; oncogene; tumor suppressor gene; probability; family history; pancreatic cancer; high risk population; mutation rate; gene insertion; founder effect; brca mutation; ashkenazi jewish; cancer family; mutation prevalence; ashkenazi jew; religious group |
| Journal Title: | Cancer |
| Volume: | 118 |
| Issue: | 2 |
| ISSN: | 0008-543X |
| Publisher: | Wiley Blackwell |
| Date Published: | 2012-01-15 |
| Start Page: | 493 |
| End Page: | 499 |
| Language: | English |
| DOI: | 10.1002/cncr.26191 |
| PROVIDER: | scopus |
| PUBMED: | 21598239 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 1 March 2012" - "CODEN: CANCA" - "Source: Scopus" |
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