Acta Univ Latv (2004) 676: 17–25

Ovarian cancer in Latvia is highly attributable to recurrent mutations in the BRCA1 gene

Abstract

Most hereditary ovarian cancers are associated with germline mutations in the BRCA1 and BRCA2 genes. The aim of this study was to estimate the role of BRCA1 mutations in ovarian cancer in Latvia and to determine the mutation profile and frequency of founder mutations in ovarian cancer patients. The analysis of the entire BRCA1 gene was carried out in 34 ovarian cancer patients by SSCP/HD analysis and automatic sequencing of the variants detected. The screening for founder mutations was performed in 75 ovarian cancer patients recruited for the Project “Genome database of Latvian population” and in 86 consecutive ovarian cancer patients treated at the Latvian Oncology Centre. Six of seven pathogenic mutation carriers identified by the analysis of the entire BRCA1 gene were carriers of founder mutations. A high proportion of BRCA1 mutation carriers was revealed also by the screening for recurrent mutations. Altogether 44 mutation carriers in 195 ovarian cancer patients were identified in our study. The high frequency (24.6 %) of two founder mutations in Latvian ovarian cancer patients allow us to suggest that testing for these mutations should be offered to all women with ovarian cancer diagnosed before the age of 65 years.