The majority of hereditary breast and ovarian cancers can be accounted for by germline mutations in the BRCA1 and BRCA2 genes. Genetic counselling and testing in high-risk patients in the Czech Republic began in 1997 in two centres (Masaryk Memorial Cancer Institute in Brno, MMCI, and the General University Hospital plus the First Faculty of Medicine, Charles University in Prague, 1FMUK). Health insurance covers testing in MMCI, whereas testing at 1FMUK is covered by research grants. The spectrum of mutations in the BRCA1 gene is similar in the Bohemian (western) and Moravian (eastern) regions of the country but the mutation spectrum observed in the BRCA2 gene is completely different. There are three BRCA1 gene mutations that are responsible for 69% and 70.4% of all BRCA1 mutations identified in women reporting to the Brno and Prague centres, respectively. The two most frequent mutations in the BRCA2 gene, which comprises 41.5% of all detected BRCA2 mutations in Brno, were not found in women tested in the Prague centre. The testing of BRCA1/BRCA2 or other possible predisposition genes for hereditary breast/ovarian cancer is determined by medical geneticists after genetic counselling. Predictive testing is offered to persons older than 18 years of age. Genetic counselling centres are easily accessible to all inhabitants in the country. Specialized preventive care is mostly organized by MMCI and the General University Hospital in Prague; however, some patients and their family members are under the care of other oncology departments and clinics. The quality of preventive care in different hospitals is currently being investigated.
- Publikační typ
- časopisecké články MeSH
This article summarizes current knowledge of the cervical carcinogenesis with a special focus on the molecular mechanisms involving the interaction of cellular tumour suppressors (p53, RB, p73) with viral oncoproteins (E6, E7). The E6-induced degradation of p53 protein results in the inhibition of apoptosis, inability to repair DNA and fixation of mutations. The p53-dependent tumourigenesis is influenced by interaction not only with E6/HPV 16, 18 but also with MDM2, bcl-2 and RB protein. The polymorphism of p53 seems to contribute to malignant transformation of cervix. On contrary, there are experimental data showing that p53 may not be the only factor playing role in malignant transformation in cervical cancer. It has been generally agreed that viral oncoprotein E6 is a critical step in the onset of malignant transformation of cervix. There is a vast number of experimental and clinical studies confirming the validity of E6 induced cervical cancer including alteration of the genotype and phenotypic characteristics of the transforming cells. The modern tools of molecular biology offer an exact diagnosis as well as relevant targets for gene therapy of the cervical cancer.
- MeSH
- lidé MeSH
- nádory děložního čípku genetika patofyziologie terapie MeSH
- onkogenní proteiny virové fyziologie MeSH
- Papillomaviridae MeSH
- tumor supresorové geny fyziologie MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- onkogenní proteiny virové MeSH
