Novel APC mutations in Czech and Slovak FAP families: clinical and genetic aspects

BACKGROUND: Germline mutations in the adenomatous polyposis gene (APC) result in familial adenomatous polyposis (FAP). FAP is an autosomal dominantly inherited disorder predisposing to colorectal cancer. Typical FAP is characterized by hundreds to thousands of colorectal adenomatous polyps and by several extracolonic manifestations. An attenuated form of polyposis (AFAP) is characterized by less than 100 adenomas and later onset of the disease. METHODS: Here, we analyzed the APC gene for germline mutations in 59 Czech and 15 Slovak FAP patients. In addition, 50 apparently APC mutation negative Czech probands and 3 probands of Slovak origin were screened for large deletions encompassing the APC gene. Mutation screening was performed using denaturing gradient gel electrophoresis and/or protein truncation test. DNA fragments showing an aberrant electrophoretic banding pattern were sequenced. Screening for large deletions was performed by multiplex ligation dependent probe amplification. The extent of deletions was analyzed using following microsatellite markers: D5S299, D5S82, D5S134 and D5S346. RESULTS: In the set of Czech and Slovak patients, we identified 46 germline mutations among 74 unrelated probands. Total mutation capture is 62,2% including large deletions. Thirty seven mutations were detected in 49 patients presenting a classical FAP phenotype (75,5%) and 9 mutations in 25 patients with attenuated FAP (36%). We report 20 novel germline APC mutations and 3 large deletions (6%) encompassing the whole-gene deletions and/or exon 14 deletion. In the patients with novel mutations, correlations of the mutation localization are discussed in context of the classical and/or attenuated phenotype of the disease. CONCLUSION: The results of the molecular genetic testing are used both in the establishment of the predictive diagnosis and in the clinical management of patients. In some cases this study has also shown the difficulty to classify clinically between the classical and the attenuated form of FAP according to the established criteria. Interfamilial and/or intrafamilial phenotype variability was also confirmed in some cases which did not fit well with predicted genotype-phenotype correlation. All these findings have to be taken into consideration both in the genetic counselling and in the patient care

Gender inequality on the labour market in the Czech Republic

Research background: Even though we live in the 21st century, where society is no longer expected to treat women and men differently, the reality is unfortunately different. Gender differences can be observed in virtually every country in the world. In some aspects of gender inequality, the Czech Republic is doing relatively well, for example, in terms of equal access to education, but in other areas it is doing much worse. In the Czech Republic, gender inequality is manifested in particular in the gender pay gap and on the labour market situation, where female unemployment is higher than male unemployment. Purpose of the article: This article analyses gender inequality in the Czech Republic on the labour market. The aim of this article is to evaluate the state, development and estimate the future direction of the labour market with an emphasis on gender inequality. Methods: Using time-series analysis of the number of applicants at the labour offices, it assesses the status and development of gender inequality in the labour market. The analysis also includes a prediction of future developments, where the author seeks an answer to the question whether the gender gap in this area is decreasing or increasing over time. Findings & Value added: The analysis showed a persistent trend of higher unemployment among women compared to men. However, this gap is decreasing in the long term

Nutritional Values of Foods on a Population of the Czech Republic

The aim of this text is to present the results of the research we carried out on a group of inhabitants of the Czech Republic who actively (or at least occasionally) engage in sports activities. The aim of the research was to analyse the consumer behavior of athletes in the Czech Republic with an emphasis on their use of health food stores and their habits in monitoring the nutritional values of food, in the content of sugar and carbohydrates in the food they consume. Excess sugar consumption; obesity; and, conversely, the issue of a healthy lifestyle and the growing interest in healthy “alternative” lifestyles, have often been a subject of debate. The research has shown, among other things, that 58% of respondents consume sugar; 70% of men and 88% of women shop at health food stores at least occasionally; and the most monitored values are calories, carbohydrates, and sugar

ENIGMA CHEK2gether Project : a comprehensive study identifies functionally impaired CHEK2 germline missense variants associated with increased breast cancer risk

Purpose: Germline pathogenic variants in CHEK2 confer moderately elevated breast cancer risk (odds ratio, OR ∼ 2.5), qualifying carriers for enhanced breast cancer screening. Besides pathogenic variants, dozens of missense CHEK2 variants of uncertain significance (VUS) have been identified, hampering the clinical utility of germline genetic testing (GGT). Experimental Design: We collected 460 CHEK2 missense VUS identified by the ENIGMA consortium in 15 countries. Their functional characterization was performed using CHEK2-complementation assays quantifying KAP1 phosphorylation and CHK2 autophosphorylation in human RPE1–CHEK2-knockout cells. Concordant results in both functional assays were used to categorize CHEK2 VUS from 12 ENIGMA case–control datasets, including 73,048 female patients with breast cancer and 88,658 ethnicity-matched controls. Results: A total of 430/460 VUS were successfully analyzed, of which 340 (79.1%) were concordant in both functional assays and categorized as functionally impaired (N = 102), functionally intermediate (N = 12), or functionally wild-type (WT)–like (N = 226). We then examined their association with breast cancer risk in the case–control analysis. The OR and 95% CI (confidence intervals) for carriers of functionally impaired, intermediate, and WT-like variants were 2.83 (95% CI, 2.35–3.41), 1.57 (95% CI, 1.41–1.75), and 1.19 (95% CI, 1.08–1.31), respectively. The meta-analysis of population-specific datasets showed similar results. Conclusions: We determined the functional consequences for the majority of CHEK2 missense VUS found in patients with breast cancer (3,660/4,436; 82.5%). Carriers of functionally impaired missense variants accounted for 0.5% of patients with breast cancer and were associated with a moderate risk similar to that of truncating CHEK2 variants. In contrast, 2.2% of all patients with breast cancer carried functionally wild-type/intermediate missense variants with no clinically relevant breast cancer risk in heterozygous carriers