International differences in the incidence of many cancer types indicate the existence of carcinogen exposures that have not yet been identified by conventional epidemiology make a substantial contribution to cancer burden1. In clear cell renal cell carcinoma, obesity, hypertension and tobacco smoking are risk factors, but they do not explain the geographical variation in its incidence2. Underlying causes can be inferred by sequencing the genomes of cancers from populations with different incidence rates and detecting differences in patterns of somatic mutations. Here we sequenced 962 clear cell renal cell carcinomas from 11 countries with varying incidence. The somatic mutation profiles differed between countries. In Romania, Serbia and Thailand, mutational signatures characteristic of aristolochic acid compounds were present in most cases, but these were rare elsewhere. In Japan, a mutational signature of unknown cause was found in more than 70% of cases but in less than 2% elsewhere. A further mutational signature of unknown cause was ubiquitous but exhibited higher mutation loads in countries with higher incidence rates of kidney cancer. Known signatures of tobacco smoking correlated with tobacco consumption, but no signature was associated with obesity or hypertension, suggesting that non-mutagenic mechanisms of action underlie these risk factors. The results of this study indicate the existence of multiple, geographically variable, mutagenic exposures that potentially affect tens of millions of people and illustrate the opportunities for new insights into cancer causation through large-scale global cancer genomics.

• MeSH
• genom lidský genetika   MeSH
• genomika MeSH
• hypertenze epidemiologie   MeSH
• incidence MeSH
• karcinom z renálních buněk * genetika   epidemiologie   chemicky indukované   MeSH
• kouření tabáku škodlivé účinky   genetika   MeSH
• kyseliny aristolochové škodlivé účinky   MeSH
• lidé MeSH
• mutace * MeSH
• mutageny * škodlivé účinky   MeSH
• nádory ledvin * genetika   epidemiologie   chemicky indukované   MeSH
• obezita epidemiologie   MeSH
• rizikové faktory MeSH
• vystavení vlivu životního prostředí * škodlivé účinky   analýza   MeSH
• zeměpis * MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Geografické názvy
• Japonsko MeSH
• Rumunsko MeSH
• Srbsko MeSH
• Thajsko MeSH

Here, in a multi-ancestry genome-wide association study meta-analysis of kidney cancer (29,020 cases and 835,670 controls), we identified 63 susceptibility regions (50 novel) containing 108 independent risk loci. In analyses stratified by subtype, 52 regions (78 loci) were associated with clear cell renal cell carcinoma (RCC) and 6 regions (7 loci) with papillary RCC. Notably, we report a variant common in African ancestry individuals ( rs7629500 ) in the 3' untranslated region of VHL, nearly tripling clear cell RCC risk (odds ratio 2.72, 95% confidence interval 2.23-3.30). In cis-expression quantitative trait locus analyses, 48 variants from 34 regions point toward 83 candidate genes. Enrichment of hypoxia-inducible factor-binding sites underscores the importance of hypoxia-related mechanisms in kidney cancer. Our results advance understanding of the genetic architecture of kidney cancer, provide clues for functional investigation and enable generation of a validated polygenic risk score with an estimated area under the curve of 0.65 (0.74 including risk factors) among European ancestry individuals.

• MeSH
• běloši genetika   MeSH
• celogenomová asociační studie * MeSH
• genetická predispozice k nemoci * MeSH
• jednonukleotidový polymorfismus * MeSH
• karcinom z renálních buněk * genetika   MeSH
• lidé MeSH
• lokus kvantitativního znaku * MeSH
• nádorový supresorový protein VHL genetika   MeSH
• nádory ledvin * genetika   MeSH
• studie případů a kontrol MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH

BACKGROUND: While much research has been done to identify individual workplace lung carcinogens, little is known about joint effects on risk when workers are exposed to multiple agents. OBJECTIVES: We investigated the pairwise joint effects of occupational exposures to asbestos, respirable crystalline silica, metals (i.e., nickel, chromium-VI), and polycyclic aromatic hydrocarbons (PAH) on lung cancer risk, overall and by major histologic subtype, while accounting for cigarette smoking. METHODS: In the international 14-center SYNERGY project, occupational exposures were assigned to 16,901 lung cancer cases and 20,965 control subjects using a quantitative job-exposure matrix (SYN-JEM). Odds ratios (ORs) and 95% confidence intervals (CIs) were computed for ever vs. never exposure using logistic regression models stratified by sex and adjusted for study center, age, and smoking habits. Joint effects among pairs of agents were assessed on multiplicative and additive scales, the latter by calculating the relative excess risk due to interaction (RERI). RESULTS: All pairwise joint effects of lung carcinogens in men were associated with an increased risk of lung cancer. However, asbestos/metals and metals/PAH resulted in less than additive effects; while the chromium-VI/silica pair showed marginally synergistic effect in relation to adenocarcinoma (RERI: 0.24; CI: 0.02, 0.46; p = 0.05). In women, several pairwise joint effects were observed for small cell lung cancer including exposure to PAH/silica (OR = 5.12; CI: 1.77, 8.48), and to asbestos/silica (OR = 4.32; CI: 1.35, 7.29), where exposure to PAH/silica resulted in a synergistic effect (RERI: 3.45; CI: 0.10, 6.8). DISCUSSION: Small or no deviation from additive or multiplicative effects was observed, but co-exposure to the selected lung carcinogens resulted generally in higher risk than exposure to individual agents, highlighting the importance to reduce and control exposure to carcinogens in workplaces and the general environment. https://doi.org/10.1289/EHP13380.

• MeSH
• azbest * toxicita   MeSH
• chrom toxicita   MeSH
• karcinogeny toxicita   MeSH
• lidé MeSH
• nádory plic * chemicky indukované   epidemiologie   MeSH
• oxid křemičitý toxicita   MeSH
• plíce MeSH
• polycyklické aromatické uhlovodíky * toxicita   MeSH
• pracovní expozice * MeSH
• studie případů a kontrol MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH

There is limited evidence regarding the exposure-effect relationship between lung-cancer risk and hexavalent chromium (Cr(VI)) or nickel. We estimated lung-cancer risks in relation to quantitative indices of occupational exposure to Cr(VI) and nickel and their interaction with smoking habits. We pooled 14 case-control studies from Europe and Canada, including 16 901 lung-cancer cases and 20 965 control subjects. A measurement-based job-exposure-matrix estimated job-year-region specific exposure levels to Cr(VI) and nickel, which were linked to the subjects' occupational histories. Odds ratios (OR) and associated 95% confidence intervals (CI) were calculated by unconditional logistic regression, adjusting for study, age group, smoking habits and exposure to other occupational lung carcinogens. Due to their high correlation, we refrained from mutually adjusting for Cr(VI) and nickel independently. In men, ORs for the highest quartile of cumulative exposure to CR(VI) were 1.32 (95% CI 1.19-1.47) and 1.29 (95% CI 1.15-1.45) in relation to nickel. Analogous results among women were: 1.04 (95% CI 0.48-2.24) and 1.29 (95% CI 0.60-2.86), respectively. In men, excess lung-cancer risks due to occupational Cr(VI) and nickel exposure were also observed in each stratum of never, former and current smokers. Joint effects of Cr(VI) and nickel with smoking were in general greater than additive, but not different from multiplicative. In summary, relatively low cumulative levels of occupational exposure to Cr(VI) and nickel were associated with increased ORs for lung cancer, particularly in men. However, we cannot rule out a combined classical measurement and Berkson-type of error structure, which may cause differential bias of risk estimates.

• MeSH
• chrom toxicita   analýza   MeSH
• lidé MeSH
• nádory plic * chemicky indukované   epidemiologie   MeSH
• nikl toxicita   analýza   MeSH
• pracovní expozice * škodlivé účinky   analýza   MeSH
• studie případů a kontrol MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH

OBJECTIVE: The article deals with occupational health protection and identification of health risks in the work environment of the Ministry of Defence (MoD) of the Czech Republic (CR). It focuses on the assessment of the incidence of occupational diseases (OD) in high-risk and risk-free occupational categories in the years 2010-2019 and compares them with data from the civilian sector. It identifies the differences between military staff and civilian employees of the MoD. METHODS: From the records of OD at the Department of Occupational Diseases of the Central Military Hospital in Prague, the data on acknowledged OD from the years 2010 to 2019 were obtained and then a retrospective analysis focusing on the classification of work at risk was performed. The obtained data were compared with the data from the Czech National Registry of Occupational Diseases (NROD), which are published annually by the National Institute of Public Health. RESULTS: In the years under review, 191 OD were confirmed at the area of MoD, 26% of all OD occurred in employees classified in the occupational risk category. Compared with the data in the NROD, where 50% of OD were found to have been caused by high-risk work, the incidence of OD caused by high-risk work in professional soldiers is lower. Only 1.6% of all OD occurred in professional soldiers whose work was classified as high-risk one. In civilian employees of MoD 24.6% of all OD were connected with high-risk work. On the contrary, the proportion of OD occurring in professional soldiers working in risk-free categories was 57.6%, in civilian employees of MoD was the ratio much lower - 16.2%. CONCLUSION: Work at the Ministry of Defence was not adequately categorized, therefore, in 2020 a new categorization of work was introduced, which together with preventive measures could contribute to reducing the incidence of OD at the Ministry of Defence.

• MeSH
• lidé MeSH
• nemoci z povolání * epidemiologie   MeSH
• ozbrojené síly * MeSH
• retrospektivní studie MeSH
• zaměstnání MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

OBJECTIVES: The aim of the analysis was to determine the probable places of coronavirus transmission in association with the work and compare the situation between 2020 and 2021. METHODS: The work analysed data from the Information System of Infectious Diseases managed by the Institute of Health Information and Statistics of the Czech Republic in the period from March 2020 - December 2021. RESULTS: 2,483,219 COVID-19 cases were officially confirmed (732,202 during 2020 and 1,338,790 in 2021), from them 140,368 (6%) represented work-related disease, 520,830 cases (21%) work-related contact, and 1,822,021 (73%) out-of-work contact. There were identified 13 occupations with the highest incidence of COVID-19 in the observed period (458,341 cases), in descending order - clerk, machinist, teacher, craftsman, worker/agency worker, driver, sales worker/cashier, warehouse worker/expediter, nurse, manager, food worker, paramedic, and social worker. Comparing 2020 and 2021, there was a difference in the ranking of occupations by incidence of disease. In 2021, the risk of infection acquiring increased for the occupations clerk, machinist, craftsman, worker/agency worker, manager, and food worker, while it decreased for the health professions (nurse, other paramedic, physician) and for social worker; 5,514 cases of COVID-19 were recognized as an occupational disease in 2020 and 2021, from them 5,483 cases (99.4%) in the health and social care economic activity sector. CONCLUSION: The available data show probable exposures to an infectious agent (without proof of specific contact with the source of the infection), of which 27% cases of COVID-19 are related to work (cases of work-related disease and work-related contact represented together the closest relationship to work). Different relevant anti-epidemic measures in the workplace have considerable practical importance for epidemic control. The use of personal protection of the mouth and nose with respirators/muffs is essential to reduce the risk of airborne transmission.

• MeSH
• COVID-19 * epidemiologie   MeSH
• lidé MeSH
• nemoci z povolání * epidemiologie   MeSH
• přenos infekce z pacienta na zdravotnického pracovníka prevence a kontrola   MeSH
• SARS-CoV-2 MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

BACKGROUND: Somatic EGFR mutations define a subset of non-small cell lung cancers (NSCLC) that have clinical impact on NSCLC risk and outcome. However, EGFR-mutation-status is often missing in epidemiologic datasets. We developed and tested pragmatic approaches to account for EGFR-mutation-status based on variables commonly included in epidemiologic datasets and evaluated the clinical utility of these approaches. METHODS: Through analysis of the International Lung Cancer Consortium (ILCCO) epidemiologic datasets, we developed a regression model for EGFR-status; we then applied a clinical-restriction approach using the optimal cut-point, and a second epidemiologic, multiple imputation approach to ILCCO survival analyses that did and did not account for EGFR-status. RESULTS: Of 35,356 ILCCO patients with NSCLC, EGFR-mutation-status was available in 4,231 patients. A model regressing known EGFR-mutation-status on clinical and demographic variables achieved a concordance index of 0.75 (95% CI, 0.74-0.77) in the training and 0.77 (95% CI, 0.74-0.79) in the testing dataset. At an optimal cut-point of probability-score = 0.335, sensitivity = 69% and specificity = 72.5% for determining EGFR-wildtype status. In both restriction-based and imputation-based regression analyses of the individual roles of BMI on overall survival of patients with NSCLC, similar results were observed between overall and EGFR-mutation-negative cohort analyses of patients of all ancestries. However, our approach identified some differences: EGFR-mutated Asian patients did not incur a survival benefit from being obese, as observed in EGFR-wildtype Asian patients. CONCLUSIONS: We introduce a pragmatic method to evaluate the potential impact of EGFR-status on epidemiological analyses of NSCLC. IMPACT: The proposed method is generalizable in the common occurrence in which EGFR-status data are missing.

• MeSH
• analýza přežití MeSH
• erbB receptory genetika   MeSH
• lidé MeSH
• mutace MeSH
• nádory plic * epidemiologie   genetika   MeSH
• nemalobuněčný karcinom plic * epidemiologie   genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

• MeSH
• Downův syndrom * MeSH
• gynekologie * MeSH
• krk MeSH
• lidé MeSH
• měření nuchální translucence MeSH
• porodnictví * MeSH
• první trimestr těhotenství MeSH
• řízení kvality MeSH
• těhotenství MeSH
• ultrasonografie prenatální MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• dopisy MeSH

BACKGROUND: Identification of screening tests for the detection of head and neck cancer (HNC) at an early stage is an important strategy to improving prognosis. Our objective was to identify plasma circulating miRNAs for the diagnosis of HNC (oral and laryngeal subsites), within a multicenter International Head and Neck Cancer Epidemiology consortium. METHODS: A high-throughput screening phase with 754 miRNAs was performed in plasma samples of 88 cases and 88 controls, followed by a validation phase of the differentially expressed miRNAs, identified in the screening, in samples of 396 cases and 396 controls. Comparison of the fold changes (FC) was carried out using the Wilcoxon rank-sum test and the Dunn multiple comparison test. RESULTS: We identified miR-151-3p (FC = 1.73, P = 0.007) as differentially expressed miRNAs in the screening and validation phase. The miR-151-3p was the only overexpressed miRNA in validation sample of patients with HNC with early stage at diagnosis (FC = 1.81, P = 0.008) and it was confirmed upregulated both in smoker early-stage cases (FC = 3.52, P = 0.024) and in nonsmoker early-stage cases (FC = 1.60, P = 0.025) compared with controls. CONCLUSIONS: We identified miR-151-3p as an early marker of HNC. This miRNA was the only upregulated in patients at early stages of the disease, independently of the smoking status. IMPACT: The prognosis for HNC is still poor. The discovery of a new diagnostic biomarker could lead to an earlier tumor discovery and therefore to an improvement in patient prognosis.

• MeSH
• cirkulující mikroRNA * MeSH
• lidé MeSH
• mikro RNA * genetika   MeSH
• nádorové biomarkery genetika   MeSH
• nádory hlavy a krku * diagnóza   genetika   MeSH
• průřezové studie MeSH
• stanovení celkové genové exprese MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH

This publication analyses current literary knowledge on selected topics in the fields of oral health and pathology, with a particular emphasis on the potential roles of the oral microbiome and preventative approaches to oral afflictions. An important association with floral dysbiosis has been documented in important oral conditions, sometimes as a predisposing factor and at other times as a result thereof. However, much remains to be elucidated regarding the specific mechanisms at play, as well as their meaning in clinical practice. Continued research into the pathophysiology of certain oral diseases is of particular importance considering how widespread they are. A specific emphasis should be placed on understanding the exact mechanisms through which the microbiota facilitates health, and when disturbed, sickness. And perhaps of most importance is the implementation of knowledge already acquired on disease prevention if the burden of oral diseases worldwide is to decline in the future.

• MeSH
• dysbióza MeSH
• lidé MeSH
• mikrobiota * MeSH
• orální zdraví * MeSH
• ústa MeSH
• veřejné zdravotnictví MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH