Profile of common prostate cancer risk variants in an unscreened Romanian population.

To find sequence variants affecting prostate cancer (PCA) susceptibility in an unscreened Romanian population we use a genome-wide association study (GWAS). The study population included 990 unrelated pathologically confirmed PCA cases and 1034 male controls. DNA was genotyped using Illumina SNP arrays, and 24.295.558 variants were imputed using the 1000 Genomes data set. An association test was performed between the imputed markers and PCA. A systematic literature review for variants associated with PCA risk identified 115 unique variants that were tested in the Romanian sample set. Thirty of the previously reported SNPs replicated (P-value < 0.05), with the strongest associations observed at: 8q24.21, 11q13.3, 6q25.3, 5p15.33, 22q13.2, 17q12 and 3q13.2. The replicated variants showing the most significant association in Romania are rs1016343 at 8q24.21 (P = 2.2 × 10-4 ), rs7929962 at 11q13.3 (P = 2.7 × 10-4 ) and rs9364554 at 6q25.2 (P = 4.7 × 10-4 ). None of the variants tested in the Romanian GWAS reached genome-wide significance (P-value <5 × 10-8 ) but 807 markers had P-values <1 × 10-4 . Here, we report the results of the first GWAS of PCA performed in a Romanian population. Our study provides evidence that a substantial fraction of previously validated PCA variants associate with risk in this unscreened Romanian population.

Identification of Lynch syndrome risk variants in the Romanian population.

Two familial forms of colorectal cancer (CRC), Lynch syndrome (LS) and familial adenomatous polyposis (FAP), are caused by rare mutations in DNA mismatch repair genes (MLH1, MSH2, MSH6, PMS2) and the genes APC and MUTYH, respectively. No information is available on the presence of high-risk CRC mutations in the Romanian population. We performed whole-genome sequencing of 61 Romanian CRC cases with a family history of cancer and/or early onset of disease, focusing the analysis on candidate variants in the LS and FAP genes. The frequencies of all candidate variants were assessed in a cohort of 688 CRC cases and 4567 controls. Immunohistochemical (IHC) staining for MLH1, MSH2, MSH6, and PMS2 was performed on tumour tissue. We identified 11 candidate variants in 11 cases; six variants in MLH1, one in MSH6, one in PMS2, and three in APC. Combining information on the predicted impact of the variants on the proteins, IHC results and previous reports, we found three novel pathogenic variants (MLH1:p.Lys84ThrfsTer4, MLH1:p.Ala586CysfsTer7, PMS2:p.Arg211ThrfsTer38), and two novel variants that are unlikely to be pathogenic. Also, we confirmed three previously published pathogenic LS variants and suggest to reclassify a previously reported variant of uncertain significance to pathogenic (MLH1:c.1559-1G>C).

PM10 and NO2 Air Pollution and Evolution of COVID-19 Cases in Romania.

Objectives:Based on the correlation between air pollution and COVID-19 incidence/mortality already existing in the literature, we aimed to develop a study to investigate the link between the average level of PM10 (particulate matter 10 - particulate matter 10 microns in diameter) and NO2 (nitrogen dioxide) concentration over five years and the cumulative incidence of COVID-19 cases per 1000 people in Romania. Methods: To assess PM10 and NO2 exposure, we determined the average value of annual PM10 and NO2 concentration for each city over five years (2015-2019). For this purpose, the average of annual PM10 and NO2 concentrations collected from monitoring stations in selected cities was calculated. Then, the annual values over five years were averaged to finally obtain the average PM10 and NO2 concentration for each city. Data on the cumulative number of confirmed cases of COVID-19 up to the 28th of September 2020 were provided by the National Centre for Surveillance and Control of Communicable Diseases (CNSCBT) of the National Institute of Public Health (INSP). The study used the cumulative incidence/hour per 1000 population on 28.09.2020. Results:According to Law no. 104/2011, the annual permissible limit value of PM10 concentration of 40 µg/m³ was not exceeded in any of the 43 cities in our study. The average for all cities was 24.0±4.8 ìg/m³, with a minimum value of average PM10 concentration of 13.9 µg/m3 measured in Alba Iulia and a maximum value of 39.1 µg/m³ in Iasi. The regression model shows that, in Bucharest, 77.9% of the variation in case incidence is explained by the variation in PM10 concentration. In order to find the number of new cases that would correspond to a cumulative incidence of 0.166, taking as an example one of the districts with a population of 259,084, the above regression model shows that an increase in the average PM10 concentration by one unit is associated with 43 new cases. Conclusion:The study demonstrates that an exposure of the population to particulate matter in atmospheric air, at low values, below the permissible limit values but for a long time (the follow-up period in our study was five years, between 2015 and 2019), can have effects on the health status of the population, which becomes much more vulnerable to external agents, in our case pathogenic microorganisms (viruses).

Exhaustion in Healthcare Workers after the First Three Waves of the COVID-19 Pandemic.

This study aims to identify the determinants of exhaustion of frontline and second-line healthcare workers (HCW) during the third wave of the COVID-19 pandemic. A case−control study was conducted based on an anonymously distributed questionnaire, which was completed by 1872 HCW. Exhaustion was assessed with a validated Romanian questionnaire. The Siegrist questionnaire was used to determine workload, reward and overcommitment. Frontline HCW reported significantly more frequent longer working hours (p = 0.0009) and a better perception of the management of the risk for infection (p = 0.0002) than second-line HCW. The effort and overcommitment scores were higher in frontline HCW (9.51 + 1.98 vs. 8.45 + 21, p < 0.001 and 16.34 ± 2.80 vs. 15.24 ± 2.94, p < 0.001, respectively) and the reward scores were lower (5.21 ± 1.522 vs. 5.99 ± 1.44, p < 0.001). In the fully adjusted regression model, age, imbalance between effort and reward, overcommitment and management of the risk of infection in the workplace were associated with the exhaustion score in each category of HCW. The number of working hours was correlated with exhaustion in frontline HCW and occupation in second-line HCW. There were more similarities than differences between frontline and second-line HCW. Even if frontline HCW had a higher risk of exhaustion, the risk was not negligible for all HCW.