AIM: The Ostomy Life Study 2019 aimed to obtain a better understanding of the challenges faced by people with stoma. METHODS: Online survey with participants from 17 countries. FINDINGS: Of the 54 614 individuals invited to take part, 5187 responded; 62% of the respondents avoided physical and social activities because of their stoma and 37% had never consulted their stoma care nurse to have the fit of their stoma product checked. In a subgroup receiving questions on leakage (n=4209), output under the baseplate and leakage onto clothes were experienced within the previous month by 76% and 26% of respondents, respectively. Higher chance of leakage was associated with an irregular stoma shape and peristomal body profile; a stoma level at or below the skin surface; and the presence of creases, folds and other changes in the peristomal area. CONCLUSION: Leakage and access to a stoma care nurse to provide the necessary care and guidance remain important concerns for individuals with a stoma.

• Klíčová slova
• Leakage, Ostomy, Patient experience, Peristomal body profile, Stoma,
• MeSH
• chirurgické stomie * škodlivé účinky   MeSH
• lidé MeSH
• průzkumy a dotazníky MeSH
• rizikové faktory MeSH
• zavedení chirurgických vývodů * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

The objectives of the study were to estimate the current exposure to cadmium (Cd) in Europe, potential differences between the countries and geographic regions, determinants of exposure and to derive European exposure levels. The basis for this work was provided by the European Human Biomonitoring Initiative (HBM4EU) which established a framework for alignment of national or regional HBM studies. For the purpose of Cd exposure assessment, studies from 9 European countries (Iceland, Denmark, Poland, Czech Republic, Croatia, Portugal, Germany, France, Luxembourg) were included and urine of 20-39 years old adults sampled in the years 2014-2021 (n = 2510). The measurements in urine were quality assured by the HBM4EU quality assurance/quality control scheme, study participants' questionnaire data were post-harmonized. Spatially resolved external data, namely Cd concentrations in soil, agricultural areas, phosphate fertilizer application, traffic density and point source Cd release were collected for the respective statistical territorial unit (NUTS). There were no distinct geographic patterns observed in Cd levels in urine, although the data revealed some differences between the specific study sites. The levels of exposure were otherwise similar between two time periods within the last decade (DEMOCOPHES - 2011-2012 vs. HBM4EU Aligned Studies, 2014-2020). The age-dependent alert values for Cd in urine were exceeded by 16% of the study participants. Exceedances in the different studies and locations ranged from 1.4% up to 42%. The studies with largest extent of exceedance were from France and Poland. Association analysis with individual food consumption data available from participants' questionnaires showed an important contribution of vegetarian diet to the overall exposure, with 35% higher levels in vegetarians as opposed to non-vegetarians. For comparison, increase in Cd levels due to smoking was 25%. Using NUTS2-level external data, positive associations between HBM data and percentage of cropland and consumption of Cd-containing mineral phosphate fertilizer were revealed, which indicates a significant contribution of mineral phosphate fertilizers to human Cd exposure through diet. In addition to diet, traffic and point source release were identified as significant sources of exposure in the study population. The findings of the study support the recommendation by EFSA to reduce Cd exposure as also the estimated mean dietary exposure of adults in the EU is close or slightly exceeding the tolerable weekly intake. It also indicates that regulations are not protecting the population sufficiently.

• Klíčová slova
• Cadmium, European exposure levels, HBM4EU, Human biomonitoring, Industrial release, NUTS, Phosphate fertilizer,
• MeSH
• dospělí MeSH
• fosfáty analýza   MeSH
• kadmium * moč   MeSH
• lidé MeSH
• mladý dospělý MeSH
• monitorování životního prostředí * metody   MeSH
• průmyslová hnojiva analýza   MeSH
• průzkumy a dotazníky MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Geografické názvy
• Evropa MeSH
• Názvy látek
• fosfáty MeSH
• kadmium * MeSH
• průmyslová hnojiva MeSH

Polycyclic aromatic hydrocarbons (PAHs) are persistent environmental pollutants with well-documented associations to adverse health effects, posing significant public health challenges across Europe. Human exposure to 13 urinary PAH metabolites was assessed in a harmonized cohort of European adults aged 20-39, representing diverse geographic regions across Europe: North (Iceland and Denmark), East (Poland and the Czech Republic), South (Croatia and Portugal), and West (France, Germany, Switzerland, and Luxembourg). This study aimed to achieve a unified understanding of PAH exposure by employing stringent participant selection criteria and harmonizing biomarker analyses by utilizing high-quality analytical protocols across multiple laboratories in Europe. Key findings revealed consistently elevated metabolite levels in smokers compared to non-smokers, with naphthalene metabolites dominating the profiles over phenanthrene and fluorene derivatives. Country-specific analyses highlighted Poland as having the highest naphthalene metabolite concentrations, while Luxembourg exhibited elevated pyrene metabolite levels. Urbanization influenced exposure, with slightly higher metabolite concentrations in town populations compared to rural areas. While sex-based stratification revealed no marked differences, gender emerged as a significant covariate in regression models, with women generally displaying higher exposure to naphthalene metabolites. Educational level further stratified exposure, with lower education correlating with increased PAH levels. Multivariate linear regression identified key exposure factors, including sampling season (i.e., summer, winter, autumn, and spring), dietary habits e.g., smoked foods, and proximity to smoke-prone environments. This dataset provides a significant baseline for evaluating the European Commission's Chemicals Strategy for Sustainability (CSS) and underscores the utility of harmonized human biomonitoring studies in informing targeted public health interventions.

• Klíčová slova
• Exposure assessment, Exposure determinants, Human biomonitoring, PAHs,
• MeSH
• biologické markery moč   MeSH
• dospělí MeSH
• látky znečišťující životní prostředí * moč   MeSH
• lidé MeSH
• mladý dospělý MeSH
• monitorování životního prostředí MeSH
• polycyklické aromatické uhlovodíky * moč   MeSH
• vystavení vlivu životního prostředí * statistika a číselné údaje   analýza   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Evropa MeSH
• Názvy látek
• biologické markery MeSH
• látky znečišťující životní prostředí * MeSH
• polycyklické aromatické uhlovodíky * MeSH

Phthalates are mainly used as plasticizers and are associated inter alia with adverse effects on reproductive functions. While more and more national programs in Europe have started monitoring internal exposure to phthalates and its substitute 1,2-Cyclohexanedicarboxylic acid (DINCH), the comparability of results from such existing human biomonitoring (HBM) studies across Europe is challenging. They differ widely in time periods, study samples, degree of geographical coverage, design, analytical methodology, biomarker selection, and analytical quality assurance level. The HBM4EU initiative has gathered existing HBM data of 29 studies from participating countries, covering all European regions and Israel. The data were prepared and aggregated by a harmonized procedure with the aim to describe-as comparably as possible-the EU-wide general population's internal exposure to phthalates from the years 2005 to 2019. Most data were available from Northern (up to 6 studies and up to 13 time points), Western (11; 19), and Eastern Europe (9; 12), e.g., allowing for the investigation of time patterns. While the bandwidth of exposure was generally similar, we still observed regional differences for Butyl benzyl phthalate (BBzP), Di(2-ethylhexyl) phthalate (DEHP), Di-isononyl phthalate (DiNP), and Di-isobutyl phthalate (DiBP) with pronounced decreases over time in Northern and Western Europe, and to a lesser degree in Eastern Europe. Differences between age groups were visible for Di-n-butyl phthalate (DnBP), where children (3 to 5-year olds and 6 to 11-year olds) had lower urinary concentrations than adolescents (12 to 19-year-olds), who in turn had lower urinary concentrations than adults (20 to 39-year-olds). This study is a step towards making internal exposures to phthalates comparable across countries, although standardized data were not available, targeting European data sets harmonized with respect to data formatting and calculation of aggregated data (such as developed within HBM4EU), and highlights further suggestions for improved harmonization in future studies.

• Klíčová slova
• HBM4EU, exposure, human biomonitoring, phthalates, pollutants,
• Publikační typ
• časopisecké články MeSH

Multiple myeloma (MM) is an incurable malignancy of plasma cells. Epidemiological studies indicate a substantial heritable component, but the underlying mechanisms remain unclear. Here, in a genome-wide association study totaling 10,906 cases and 366,221 controls, we identify 35 MM risk loci, 12 of which are novel. Through functional fine-mapping and Mendelian randomization, we uncover two causal mechanisms for inherited MM risk: longer telomeres; and elevated levels of B-cell maturation antigen (BCMA) and interleukin-5 receptor alpha (IL5RA) in plasma. The largest increase in BCMA and IL5RA levels is mediated by the risk variant rs34562254-A at TNFRSF13B. While individuals with loss-of-function variants in TNFRSF13B develop B-cell immunodeficiency, rs34562254-A exerts a gain-of-function effect, increasing MM risk through amplified B-cell responses. Our results represent an analysis of genetic MM predisposition, highlighting causal mechanisms contributing to MM development.

• MeSH
• B-lymfocyty imunologie   metabolismus   MeSH
• celogenomová asociační studie * MeSH
• genetická predispozice k nemoci * MeSH
• jednonukleotidový polymorfismus * MeSH
• lidé MeSH
• maturační antigen B-buněk * genetika   MeSH
• mendelovská randomizace MeSH
• mnohočetný myelom * genetika   MeSH
• receptor TACI genetika   MeSH
• studie případů a kontrol MeSH
• telomery genetika   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• maturační antigen B-buněk * MeSH
• receptor TACI MeSH
• TNFRSF13B protein, human MeSH Prohlížeč

Multiple myeloma (MM) arises following malignant proliferation of plasma cells in the bone marrow, that secrete high amounts of specific monoclonal immunoglobulins or light chains, resulting in the massive production of unfolded or misfolded proteins. Autophagy can have a dual role in tumorigenesis, by eliminating these abnormal proteins to avoid cancer development, but also ensuring MM cell survival and promoting resistance to treatments. To date no studies have determined the impact of genetic variation in autophagy-related genes on MM risk. We performed meta-analysis of germline genetic data on 234 autophagy-related genes from three independent study populations including 13,387 subjects of European ancestry (6863 MM patients and 6524 controls) and examined correlations of statistically significant single nucleotide polymorphisms (SNPs; p < 1 × 10-9) with immune responses in whole blood, peripheral blood mononuclear cells (PBMCs), and monocyte-derived macrophages (MDM) from a large population of healthy donors from the Human Functional Genomic Project (HFGP). We identified SNPs in six loci, CD46, IKBKE, PARK2, ULK4, ATG5, and CDKN2A associated with MM risk (p = 4.47 × 10-4-5.79 × 10-14). Mechanistically, we found that the ULK4rs6599175 SNP correlated with circulating concentrations of vitamin D3 (p = 4.0 × 10-4), whereas the IKBKErs17433804 SNP correlated with the number of transitional CD24+CD38+ B cells (p = 4.8 × 10-4) and circulating serum concentrations of Monocyte Chemoattractant Protein (MCP)-2 (p = 3.6 × 10-4). We also found that the CD46rs1142469 SNP correlated with numbers of CD19+ B cells, CD19+CD3- B cells, CD5+IgD- cells, IgM- cells, IgD-IgM- cells, and CD4-CD8- PBMCs (p = 4.9 × 10-4-8.6 × 10-4) and circulating concentrations of interleukin (IL)-20 (p = 0.00082). Finally, we observed that the CDKN2Ars2811710 SNP correlated with levels of CD4+EMCD45RO+CD27- cells (p = 9.3 × 10-4). These results suggest that genetic variants within these six loci influence MM risk through the modulation of specific subsets of immune cells, as well as vitamin D3-, MCP-2-, and IL20-dependent pathways.

• Klíčová slova
• autophagy, genetic susceptibility, genetic variants, multiple myeloma,
• MeSH
• autofagie MeSH
• biologické markery MeSH
• imunoglobulin M MeSH
• leukocyty mononukleární patologie   MeSH
• lidé MeSH
• mnohočetný myelom * genetika   patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• Názvy látek
• biologické markery MeSH
• imunoglobulin M MeSH

While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between the AURKA-HMMR-TPX2-TUBG1 functional module and risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Forty-one single nucleotide polymorphisms (SNPs) were genotyped in 15,252 BRCA1 and 8,211 BRCA2 mutation carriers and subsequently analyzed using a retrospective likelihood approach. The association of HMMR rs299290 with breast cancer risk in BRCA1 mutation carriers was confirmed: per-allele hazard ratio (HR) = 1.10, 95% confidence interval (CI) 1.04-1.15, p = 1.9 x 10(-4) (false discovery rate (FDR)-adjusted p = 0.043). Variation in CSTF1, located next to AURKA, was also found to be associated with breast cancer risk in BRCA2 mutation carriers: rs2426618 per-allele HR = 1.10, 95% CI 1.03-1.16, p = 0.005 (FDR-adjusted p = 0.045). Assessment of pairwise interactions provided suggestions (FDR-adjusted pinteraction values > 0.05) for deviations from the multiplicative model for rs299290 and CSTF1 rs6064391, and rs299290 and TUBG1 rs11649877 in both BRCA1 and BRCA2 mutation carriers. Following these suggestions, the expression of HMMR and AURKA or TUBG1 in sporadic breast tumors was found to potentially interact, influencing patients' survival. Together, the results of this study support the hypothesis of a causative link between altered function of AURKA-HMMR-TPX2-TUBG1 and breast carcinogenesis in BRCA1/2 mutation carriers.

• MeSH
• alfa receptor estrogenů metabolismus   MeSH
• antigeny CD44 genetika   MeSH
• Aurora kinasa A genetika   MeSH
• extracelulární matrix - proteiny genetika   MeSH
• genetická predispozice k nemoci genetika   MeSH
• genetické lokusy genetika   MeSH
• geny BRCA1 * MeSH
• geny BRCA2 * MeSH
• jaderné proteiny genetika   MeSH
• jednonukleotidový polymorfismus MeSH
• karcinogeneze genetika   MeSH
• lidé MeSH
• mléčné žlázy lidské metabolismus   MeSH
• molekulární evoluce MeSH
• mutace * MeSH
• nádory prsu enzymologie   genetika   patologie   MeSH
• pravděpodobnostní funkce MeSH
• proteiny asociované s mikrotubuly genetika   MeSH
• proteiny buněčného cyklu genetika   MeSH
• retrospektivní studie MeSH
• tubulin genetika   MeSH
• Check Tag
• lidé 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
• Research Support, U.S. Gov't, Non-P.H.S. MeSH
• Názvy látek
• alfa receptor estrogenů MeSH
• antigeny CD44 MeSH
• Aurora kinasa A MeSH
• extracelulární matrix - proteiny MeSH
• hyaluronan-mediated motility receptor MeSH Prohlížeč
• jaderné proteiny MeSH
• proteiny asociované s mikrotubuly MeSH
• proteiny buněčného cyklu MeSH
• TPX2 protein, human MeSH Prohlížeč
• TUBG1 protein, human MeSH Prohlížeč
• tubulin MeSH

IMPORTANCE: Limited information about the relationship between specific mutations in BRCA1 or BRCA2 (BRCA1/2) and cancer risk exists. OBJECTIVE: To identify mutation-specific cancer risks for carriers of BRCA1/2. DESIGN, SETTING, AND PARTICIPANTS: Observational study of women who were ascertained between 1937 and 2011 (median, 1999) and found to carry disease-associated BRCA1 or BRCA2 mutations. The international sample comprised 19,581 carriers of BRCA1 mutations and 11,900 carriers of BRCA2 mutations from 55 centers in 33 countries on 6 continents. We estimated hazard ratios for breast and ovarian cancer based on mutation type, function, and nucleotide position. We also estimated RHR, the ratio of breast vs ovarian cancer hazard ratios. A value of RHR greater than 1 indicated elevated breast cancer risk; a value of RHR less than 1 indicated elevated ovarian cancer risk. EXPOSURES: Mutations of BRCA1 or BRCA2. MAIN OUTCOMES AND MEASURES: Breast and ovarian cancer risks. RESULTS: Among BRCA1 mutation carriers, 9052 women (46%) were diagnosed with breast cancer, 2317 (12%) with ovarian cancer, 1041 (5%) with breast and ovarian cancer, and 7171 (37%) without cancer. Among BRCA2 mutation carriers, 6180 women (52%) were diagnosed with breast cancer, 682 (6%) with ovarian cancer, 272 (2%) with breast and ovarian cancer, and 4766 (40%) without cancer. In BRCA1, we identified 3 breast cancer cluster regions (BCCRs) located at c.179 to c.505 (BCCR1; RHR = 1.46; 95% CI, 1.22-1.74; P = 2 × 10(-6)), c.4328 to c.4945 (BCCR2; RHR = 1.34; 95% CI, 1.01-1.78; P = .04), and c. 5261 to c.5563 (BCCR2', RHR = 1.38; 95% CI, 1.22-1.55; P = 6 × 10(-9)). We also identified an ovarian cancer cluster region (OCCR) from c.1380 to c.4062 (approximately exon 11) with RHR = 0.62 (95% CI, 0.56-0.70; P = 9 × 10(-17)). In BRCA2, we observed multiple BCCRs spanning c.1 to c.596 (BCCR1; RHR = 1.71; 95% CI, 1.06-2.78; P = .03), c.772 to c.1806 (BCCR1'; RHR = 1.63; 95% CI, 1.10-2.40; P = .01), and c.7394 to c.8904 (BCCR2; RHR = 2.31; 95% CI, 1.69-3.16; P = .00002). We also identified 3 OCCRs: the first (OCCR1) spanned c.3249 to c.5681 that was adjacent to c.5946delT (6174delT; RHR = 0.51; 95% CI, 0.44-0.60; P = 6 × 10(-17)). The second OCCR spanned c.6645 to c.7471 (OCCR2; RHR = 0.57; 95% CI, 0.41-0.80; P = .001). Mutations conferring nonsense-mediated decay were associated with differential breast or ovarian cancer risks and an earlier age of breast cancer diagnosis for both BRCA1 and BRCA2 mutation carriers. CONCLUSIONS AND RELEVANCE: Breast and ovarian cancer risks varied by type and location of BRCA1/2 mutations. With appropriate validation, these data may have implications for risk assessment and cancer prevention decision making for carriers of BRCA1 and BRCA2 mutations.

• MeSH
• dospělí MeSH
• genetická predispozice k nemoci * MeSH
• geny BRCA1 * MeSH
• geny BRCA2 * MeSH
• heterozygot MeSH
• lidé středního věku MeSH
• lidé MeSH
• mutace * MeSH
• nádory prsu genetika   MeSH
• nádory vaječníků genetika   MeSH
• nukleotidy MeSH
• rizikové faktory MeSH
• věk při počátku nemoci MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• nukleotidy MeSH