Vysoká frekvence mutací v genech BKCA1 a BKCA2 v českých rodinách s dědičnou formou nádorů prsu a vaječníku

A HIGH OCCURRENCE OF BRCA1 AND BRCA2 MUTATIONS AMONG CZECH HEREDITARY BREAST AND BREAST-OVARIAN CANCER FAMILIES

Background.
About 5-10 % of breast and ovarian cancer can be of hereditary origin. Germline mutations in BRCA1 or BRCA2 and probably other yet unknown genes may cause predisposition to these cancers.Methods and Results. Molecular genetic testing of BRCA1 and BRCA2 genes in 21 high-risk breast and breast/ovarian cancer families was performed in order to find the types and the frequency of mutations in the South Moravian region of the Czech Republic. A germline mutation was found in 12 of 21 tested families (57 %), 9 mutations in BRCA1 gene and 3 mutations in BRCA2 gene. In 4 unrelated families the same germline mutation in the BRCA1 gene (5382insC) was identified. In 12 families diagnosed with breast cancer only syndrome 3 families harbouring BRCA1 mutations and 3 families harbouring BRCA2 mutations were found. In 9 families with breast-ovarian cancer syndrome 6 families carrying BRCA1 mutations were detected.Conclusion. Molecular genetic testing of BRCA1 and BRCA2 genes in high-risk women with breast/ovarian cancer is effective in determining genetic predisposition to cancer. Spectrum of mutations found in both genes is variable and further investigation is needed for estimation of more frequent or „founder“ mutations. The genetic counselling and preventive clinical follow-up of gene carriers has to be part of the genetic program.

Key words:
hereditary breast/ovarian cancer, genes, BRCA1, BRCA2, genetic counselling, molecular genetic testing, mutation carriers.