High incidence of BRCA1-2 germline mutations, previous breast cancer and familial cancer history in Jewish patients with uterine serous papillary carcinoma

Objective: To test the carrier status of the three germline founder mutations in Jewish patients with uterine serous papillary carcinoma (USPC) and to evaluate its association to their personal and familial cancer records. Methods: Retrospective analysis of histologically confirmed USPC Jewish patients diagnosed between April 1, 1997 and December 31, 2003. All cases were genetically tested for the three BRCA1-2 founder germline mutations (185delAG and 5382insC in BRCA1 and 6174delT in BRCA2). The analysis was performed on genomic DNA extracted from whole blood or paraffin embedded normal tissue of these patients, employing PCR amplification of target sequences and differential digestion with restriction enzymes. The carrier frequency was compared to the known population frequency of these mutations. Results: The study group comprised 22 Jewish patients with USPC diagnosed within this timeframe. The mean age was 71.8 years (range 56-79). FIGO surgical stage distribution revealed 59% at stages III-IV. Seven USPC patients (32%) with a previous diagnosis of breast cancer were identified. Familial cancer history was recorded in 23% of the patients (four with breast cancer and one with ovarian cancer). DNA analysis revealed six BRCA1-2 germline mutation carriers (27%) as follows: three with BRCA2-6174delT, two with BRCA1-185delAG, and one with BRCA1-5382insC mutation. Three of the carriers had a previous diagnosis of breast cancer. Four carriers had familial cancer history in first-degree relative (three with breast cancer and one with ovarian cancer). Conclusions: The high rate of BRCA germline mutations in USPC patients observed in the present study, coupled with the strong personal and familial cancer history as well as the histological and clinical resemblance to the ovarian cancer, may indicate that USPC is a part or an expression of the hereditary breast-ovarian cancer syndrome. This option may have implications in our clinical recommendations for non-affected BRCA1-2 carriers.