OBJECTIVES: We investigated whether social gradient in all-cause mortality in the Czech Republic changed during the postcommunist transition by comparing two cohorts, recruited before and after the political changes in 1989. METHODS: Participants (aged 25-64 years) in two population surveys (n=2530 in 1985, n=2294 in 1992) were followed up for mortality for 15 years (291 and 281 deaths, respectively). Education was classified into attainment categories and years of schooling (both continuous and in tertiles). Cox regression was used to estimate HR of death by educational indices in each cohort over a 15-year follow-up. RESULTS: All three educational variables were significantly associated with reduced risk of death in both cohorts when men and women were combined; for example, the adjusted HRs of death in the highest versus lowest tertile of years of schooling were 0.65 (95% CI 0.47 to 0.89) in 1985 and 0.67 (95% CI 0.48 to 0.93) in 1992. Adjustment for covariates attenuated the gradients. In sex-specific analysis, the gradient was more pronounced and statistically significant in men. There were no significant interactions between cohort and educational indices. CONCLUSIONS: The educational gradient in mortality did not differ between the two cohorts (1985 vs 1992), suggesting no major increase in educational inequality during the early stage of postcommunist transition. Further research is needed to understand trends in health inequalities during socioeconomic transitions.

• MeSH
• kohortové studie MeSH
• lidé MeSH
• příčina smrti * MeSH
• socioekonomické faktory MeSH
• stupeň vzdělání MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH

Heterozygous germline BRCA2 mutations predispose to breast, ovarian, pancreatic and other types of cancer. The presence of a pathogenic mutation in patients or their family members warrants close surveillance or prophylactic surgery. Besides clearly pathogenic mutations, variants leading only to a single amino acid substitution are often identified. The influence of such variants on cancer risk is often unknown, making their presence a major clinical problem. When genetic methods are insufficient to classify these variants, functional assays with various cellular models are performed. We developed and applied a new syngeneic model of human cancer cells to test all variants of unknown significance in exon 18 identified by genetic testing of high-risk cancer patients in the Czech Republic, via introduction of constructs containing each of these variants into the wild-type allele of BRCA2-heterozygous DLD1 cells (BRCA2wt/Δex11). We found unaffected DNA repair function of BRCA2 in cell lines BRCA27997G>C/Δex11, BRCA28111C>T/Δex11, BRCA28149G>T/Δex11, BRCA28182G>A/Δex11, and BRCA28182G>T/Δex11, whereas the cell line BRCA28168A>G/Δex11 and the nonsense mutation carrying line BRCA28305G>T/Δex11 did affect protein function. Targeting the BRCA2 wild-type allele with a construct carrying the variant c.7988A> G resulted in incorporation exclusively into the already defective allele in all viable clones, strongly suggesting a detrimental phenotype. Our model thus offers a valuable tool for the functional evaluation of unclassified variants in the BRCA2 gene and provides a stable and distributable cellular resource for further research.

• MeSH
• anamnéza MeSH
• biologické modely * MeSH
• dospělí MeSH
• exony genetika   MeSH
• genetická predispozice k nemoci * MeSH
• genetické testování metody   MeSH
• hodnocení rizik metody   MeSH
• lidé středního věku MeSH
• lidé MeSH
• Markovovy řetězce MeSH
• mutace MeSH
• mutační analýza DNA metody   MeSH
• nádorové buněčné linie MeSH
• nádory diagnóza   genetika   MeSH
• protein BRCA2 genetika   MeSH
• senioři MeSH
• studie proveditelnosti MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH