Prevalence and clinical correlations of BRCA1/BRCA2 unclassified variant carriers among unselected primary ovarian cancer cases - preliminary report

The objective of this study was to determine the prevalence of BRCA1 and BRCA2 gene mutations in unselected ovarian cancer patients, and to analyse clinical and pathological features of ovarian cancer unclassified variant mutation carriers in comparison with BRCA1 pathogenic mutation carriers and sporadic cases. A consecutive sample of 205 women with primary ovarian cancer was screened for mutations in the BRCA1 and BRCA2 genes using a direct test for small deletions and insertions, conformational sensitive gel electrophoresis and direct sequencing. Data regarding medical and familial history were collected using questionnaires. Clinical and pathological data were extracted from medical records. Unclassified variants and polymorphic mutations accounted for 8% (n = 16) and 6% (n = 13) of all cases, respectively. BRCA1 pathogenic mutations were found in 18 (9%) patients. None were found in BRCA2. The mean age of onset for BRCA1-associated tumours was 43.1 years (standard deviation (SD: 7.3) whereas in the patients with an unclassified variant, polymorphism, or no detectable gene changes, the mean age of onset ranged from 49.5-56.4 years. The most significant predictors for pathogenic or unclassified variant changes in BRCA1 in ovarian cancer patients were a younger age of onset and a history of hyperthyroidism and infertility. Except for infertility and hyperthyroidism, unclassified variant-linked ovarian tumours share features with sporadic tumours rather than with BRCA1 pathogenic mutations.