As one of the core elements of the European Human Biomonitoring Initiative (HBM4EU) a human biomonitoring (HBM) survey was conducted in 23 countries to generate EU-wide comparable HBM data. This survey has built on existing HBM capacity in Europe by aligning national or regional HBM studies, referred to as the HBM4EU Aligned Studies. The HBM4EU Aligned Studies included a total of 10,795 participants of three age groups: (i) 3,576 children aged 6-12 years, (ii) 3,117 teenagers aged 12-18 years and (iii) 4,102 young adults aged 20-39 years. The participants were recruited between 2014 and 2021 in 11-12 countries per age group, geographically distributed across Europe. Depending on the age group, internal exposure to phthalates and the substitute DINCH, halogenated and organophosphorus flame retardants, per- and polyfluoroalkyl substances (PFASs), cadmium, bisphenols, polycyclic aromatic hydrocarbons (PAHs), arsenic species, acrylamide, mycotoxins (deoxynivalenol (total DON)), benzophenones and selected pesticides was assessed by measuring substance specific biomarkers subjected to stringent quality control programs for chemical analysis. For substance groups analyzed in different age groups higher average exposure levels were observed in the youngest age group, i.e., phthalates/DINCH in children versus teenagers, acrylamide and pesticides in children versus adults, benzophenones in teenagers versus adults. Many biomarkers in teenagers and adults varied significantly according to educational attainment, with higher exposure levels of bisphenols, phthalates, benzophenones, PAHs and acrylamide in participants (from households) with lower educational attainment, while teenagers from households with higher educational attainment have higher exposure levels for PFASs and arsenic. In children, a social gradient was only observed for the non-specific pyrethroid metabolite 3-PBA and di-isodecyl phthalate (DiDP), with higher levels in children from households with higher educational attainment. Geographical variations were seen for all exposure biomarkers. For 15 biomarkers, the available health-based HBM guidance values were exceeded with highest exceedance rates for toxicologically relevant arsenic in teenagers (40%), 3-PBA in children (36%), and between 11 and 14% for total DON, Σ (PFOA + PFNA + PFHxS + PFOS), bisphenol S and cadmium. The infrastructure and harmonized approach succeeded in obtaining comparable European wide internal exposure data for a prioritized set of 11 chemical groups. These data serve as a reference for comparison at the global level, provide a baseline to compare the efficacy of the European Commission's chemical strategy for sustainability and will give leverage to national policy makers for the implementation of targeted measures.

• MeSH
• akrylamidy MeSH
• arsen * analýza   MeSH
• biologické markery MeSH
• biologický monitoring MeSH
• dítě MeSH
• fluorokarbony * analýza   MeSH
• kadmium analýza   MeSH
• látky znečišťující životní prostředí * analýza   MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• pesticidy * analýza   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Renal cell carcinoma (RCC) has an undisputed genetic component and a stable 2:1 male to female sex ratio in its incidence across populations, suggesting possible sexual dimorphism in its genetic susceptibility. We conducted the first sex-specific genome-wide association analysis of RCC for men (3227 cases, 4916 controls) and women (1992 cases, 3095 controls) of European ancestry from two RCC genome-wide scans and replicated the top findings using an additional series of men (2261 cases, 5852 controls) and women (1399 cases, 1575 controls) from two independent cohorts of European origin. Our study confirmed sex-specific associations for two known RCC risk loci at 14q24.2 (DPF3) and 2p21(EPAS1). We also identified two additional suggestive male-specific loci at 6q24.3 (SAMD5, male odds ratio (ORmale) = 0.83 [95% CI = 0.78-0.89], Pmale = 1.71 × 10-8 compared with female odds ratio (ORfemale) = 0.98 [95% CI = 0.90-1.07], Pfemale = 0.68) and 12q23.3 (intergenic, ORmale = 0.75 [95% CI = 0.68-0.83], Pmale = 1.59 × 10-8 compared with ORfemale = 0.93 [95% CI = 0.82-1.06], Pfemale = 0.21) that attained genome-wide significance in the joint meta-analysis. Herein, we provide evidence of sex-specific associations in RCC genetic susceptibility and advocate the necessity of larger genetic and genomic studies to unravel the endogenous causes of sex bias in sexually dimorphic traits and diseases like RCC.

• MeSH
• celogenomová asociační studie * MeSH
• genetická predispozice k nemoci * MeSH
• jednonukleotidový polymorfismus MeSH
• karcinom z renálních buněk epidemiologie   genetika   MeSH
• lidé MeSH
• lokus kvantitativního znaku MeSH
• nádory ledvin epidemiologie   genetika   MeSH
• odds ratio MeSH
• sexuální faktory MeSH
• výpočetní biologie MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

BACKGROUND: Several obesity-related factors have been associated with renal cell carcinoma (RCC), but it is unclear which individual factors directly influence risk. We addressed this question using genetic markers as proxies for putative risk factors and evaluated their relation to RCC risk in a mendelian randomization (MR) framework. This methodology limits bias due to confounding and is not affected by reverse causation. METHODS AND FINDINGS: Genetic markers associated with obesity measures, blood pressure, lipids, type 2 diabetes, insulin, and glucose were initially identified as instrumental variables, and their association with RCC risk was subsequently evaluated in a genome-wide association study (GWAS) of 10,784 RCC patients and 20,406 control participants in a 2-sample MR framework. The effect on RCC risk was estimated by calculating odds ratios (ORSD) for a standard deviation (SD) increment in each risk factor. The MR analysis indicated that higher body mass index increases the risk of RCC (ORSD: 1.56, 95% confidence interval [CI] 1.44-1.70), with comparable results for waist-to-hip ratio (ORSD: 1.63, 95% CI 1.40-1.90) and body fat percentage (ORSD: 1.66, 95% CI 1.44-1.90). This analysis further indicated that higher fasting insulin (ORSD: 1.82, 95% CI 1.30-2.55) and diastolic blood pressure (DBP; ORSD: 1.28, 95% CI 1.11-1.47), but not systolic blood pressure (ORSD: 0.98, 95% CI 0.84-1.14), increase the risk for RCC. No association with RCC risk was seen for lipids, overall type 2 diabetes, or fasting glucose. CONCLUSIONS: This study provides novel evidence for an etiological role of insulin in RCC, as well as confirmatory evidence that obesity and DBP influence RCC risk.

• MeSH
• celogenomová asociační studie MeSH
• diabetes mellitus 2. typu komplikace   MeSH
• genetické markery MeSH
• index tělesné hmotnosti MeSH
• inzulin krev   MeSH
• karcinom z renálních buněk etiologie   genetika   MeSH
• krevní glukóza analýza   MeSH
• krevní tlak MeSH
• lidé MeSH
• lipidy krev   MeSH
• mendelovská randomizace MeSH
• nádory ledvin etiologie   genetika   MeSH
• obezita komplikace   genetika   MeSH
• rizikové faktory MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, N.I.H., Intramural MeSH

Per- and polyfluoroalkyl substances (PFASs) are man-made chemicals that contain at least one perfluoroalkyl moiety, [Formula: see text]. To date, over 4,000 unique PFASs have been used in technical applications and consumer products, and some of them have been detected globally in human and wildlife biomonitoring studies. Because of their extraordinary persistence, human and environmental exposure to PFASs will be a long-term source of concern. Some PFASs such as perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) have been investigated extensively and thus regulated, but for many other PFASs, knowledge about their current uses and hazards is still very limited or missing entirely. To address this problem and prepare an action plan for the assessment and management of PFASs in the coming years, a group of more than 50 international scientists and regulators held a two-day workshop in November, 2017. The group identified both the respective needs of and common goals shared by the scientific and the policy communities, made recommendations for cooperative actions, and outlined how the science-policy interface regarding PFASs can be strengthened using new approaches for assessing and managing highly persistent chemicals such as PFASs. https://doi.org/10.1289/EHP4158.

• MeSH
• fluorokarbony * MeSH
• látky znečišťující životní prostředí * MeSH
• lidé MeSH
• monitorování životního prostředí MeSH
• vystavení vlivu životního prostředí prevence a kontrola   MeSH
• znečištění životního prostředí prevence a kontrola   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: Relative telomere length in peripheral blood leukocytes has been evaluated as a potential biomarker for renal cell carcinoma (RCC) risk in several studies, with conflicting findings. OBJECTIVE: We performed an analysis of genetic variants associated with leukocyte telomere length to assess the relationship between telomere length and RCC risk using Mendelian randomization, an approach unaffected by biases from temporal variability and reverse causation that might have affected earlier investigations. DESIGN, SETTING, AND PARTICIPANTS: Genotypes from nine telomere length-associated variants for 10 784 cases and 20 406 cancer-free controls from six genome-wide association studies (GWAS) of RCC were aggregated into a weighted genetic risk score (GRS) predictive of leukocyte telomere length. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Odds ratios (ORs) relating the GRS and RCC risk were computed in individual GWAS datasets and combined by meta-analysis. RESULTS AND LIMITATIONS: Longer genetically inferred telomere length was associated with an increased risk of RCC (OR=2.07 per predicted kilobase increase, 95% confidence interval [CI]:=1.70-2.53, p<0.0001). As a sensitivity analysis, we excluded two telomere length variants in linkage disequilibrium (R2>0.5) with GWAS-identified RCC risk variants (rs10936599 and rs9420907) from the telomere length GRS; despite this exclusion, a statistically significant association between the GRS and RCC risk persisted (OR=1.73, 95% CI=1.36-2.21, p<0.0001). Exploratory analyses for individual histologic subtypes suggested comparable associations with the telomere length GRS for clear cell (N=5573, OR=1.93, 95% CI=1.50-2.49, p<0.0001), papillary (N=573, OR=1.96, 95% CI=1.01-3.81, p=0.046), and chromophobe RCC (N=203, OR=2.37, 95% CI=0.78-7.17, p=0.13). CONCLUSIONS: Our investigation adds to the growing body of evidence indicating some aspect of longer telomere length is important for RCC risk. PATIENT SUMMARY: Telomeres are segments of DNA at chromosome ends that maintain chromosomal stability. Our study investigated the relationship between genetic variants associated with telomere length and renal cell carcinoma risk. We found evidence suggesting individuals with inherited predisposition to longer telomere length are at increased risk of developing renal cell carcinoma.

• MeSH
• celogenomová asociační studie MeSH
• fenotyp MeSH
• genetická predispozice k nemoci MeSH
• hodnocení rizik MeSH
• homeostáza telomer * MeSH
• jednonukleotidový polymorfismus * MeSH
• karcinom z renálních buněk krev   genetika   patologie   MeSH
• leukocyty chemie   MeSH
• lidé MeSH
• mendelovská randomizace MeSH
• nádory ledvin krev   genetika   patologie   MeSH
• odds ratio MeSH
• rizikové faktory MeSH
• studie případů a kontrol MeSH
• telomery genetika   patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, N.I.H., Intramural MeSH

Previous genome-wide association studies (GWAS) have identified six risk loci for renal cell carcinoma (RCC). We conducted a meta-analysis of two new scans of 5,198 cases and 7,331 controls together with four existing scans, totalling 10,784 cases and 20,406 controls of European ancestry. Twenty-four loci were tested in an additional 3,182 cases and 6,301 controls. We confirm the six known RCC risk loci and identify seven new loci at 1p32.3 (rs4381241, P=3.1 × 10-10), 3p22.1 (rs67311347, P=2.5 × 10-8), 3q26.2 (rs10936602, P=8.8 × 10-9), 8p21.3 (rs2241261, P=5.8 × 10-9), 10q24.33-q25.1 (rs11813268, P=3.9 × 10-8), 11q22.3 (rs74911261, P=2.1 × 10-10) and 14q24.2 (rs4903064, P=2.2 × 10-24). Expression quantitative trait analyses suggest plausible candidate genes at these regions that may contribute to RCC susceptibility.

• MeSH
• běloši genetika   MeSH
• celogenomová asociační studie * MeSH
• dospělí MeSH
• fenotyp MeSH
• genetická predispozice k nemoci * MeSH
• genetické lokusy MeSH
• jednonukleotidový polymorfismus MeSH
• karcinom z renálních buněk genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nádory ledvin genetika   MeSH
• senioři MeSH
• zárodečné mutace MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

Occupation as a welder has been associated with a 25%-40% increase in lung cancer risk. This study aims to elucidate to what extent confounding by smoking and asbestos drives this association and to evaluate the role of welding-related exposures such as chromium. The study included 2,197 male incident lung cancer cases and 2,295 controls from Romania, Hungary, Poland, Russia, Slovakia, the Czech Republic, and the United Kingdom from 1998 to 2001. Information on risk factors was collected through face-to-face interviews. Experts assessed exposure to 70 agents, and risk estimates were adjusted for smoking and occupational exposures. Occupation as a welder/flame cutter (prevalence controls: 3.7%) was associated with an odds ratio of 1.36 (95% confidence interval (CI): 1.00, 1.86) after adjustment for smoking and occupational exposures including asbestos. An odds ratio of 1.18 (95% CI: 1.01, 1.38) was found for welding fumes (prevalence controls: 22.8%), increasing to 1.38 for more than 25 exposure years (95% CI: 1.09, 1.75). A duration-response association was also observed for mild steel welding without chromium exposure. In this population, occupational exposure to welding fumes accounted for approximately 4% of lung cancer cases, to which both stainless and mild steel welding contributed equally. Given that welding remains a common task for many workers, exposure to welding fumes represents an important risk factor for lung cancer.

• MeSH
• dospělí MeSH
• kouření škodlivé účinky   epidemiologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory plic epidemiologie   etiologie   MeSH
• nemoci z povolání epidemiologie   MeSH
• odds ratio MeSH
• pracovní expozice škodlivé účinky   statistika a číselné údaje   MeSH
• prevalence MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• svařování statistika a číselné údaje   MeSH
• věkové faktory 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
• Maďarsko MeSH
• Polsko MeSH
• Rumunsko MeSH
• Rusko MeSH
• Slovenská republika MeSH
• Spojené království MeSH