The skin exposome, defined as the totality of environmental exposures from conception to death that can induce or modify various skin conditions, compiles environmental, lifestyle and psychosocial ...exposures, as well as the resulting internal biological and physiological responses to these exposures. Biomonitoring can be used to obtain information on the internal dose of pollutants. The concentration of biomarkers in body fluids is highly variable over time due to differential elimination kinetics of chemicals, whereas they accumulate in hair. Hair analysis thus provides information on cumulative exposure over a longer period of time, and so can be used for assessing chronic exposure to pollutants. Studies on hair samples collected from 204 women living in two cities in China with different levels of pollution demonstrated that hair damage and the skin microbiome are biomarkers of a polluted city and long‐term exposure to pollution and UV can increase signs of facial ageing. Adopting an exposome approach to skin health requires assessing multiple exposures and biological consequences, possibly in relation to longitudinally followed‐up health outcomes. Leveraging “omics” data (e.g. metabolomics, proteomics, genomics and microbiome) and big data analytics, in particular multivariate analysis, will help to further understand the impact of pollution on skin and the combined effects with other exposome factors, including solar radiation and other environmental exposures.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Summary Background In 2011, WHO member states signed up to the 25 × 25 initiative, a plan to cut mortality due to non-communicable diseases by 25% by 2025. However, socioeconomic factors influencing ...non-communicable diseases have not been included in the plan. In this study, we aimed to compare the contribution of socioeconomic status to mortality and years-of-life-lost with that of the 25 × 25 conventional risk factors. Methods We did a multicohort study and meta-analysis with individual-level data from 48 independent prospective cohort studies with information about socioeconomic status, indexed by occupational position, 25 × 25 risk factors (high alcohol intake, physical inactivity, current smoking, hypertension, diabetes, and obesity), and mortality, for a total population of 1 751 479 (54% women) from seven high-income WHO member countries. We estimated the association of socioeconomic status and the 25 × 25 risk factors with all-cause mortality and cause-specific mortality by calculating minimally adjusted and mutually adjusted hazard ratios HR and 95% CIs. We also estimated the population attributable fraction and the years of life lost due to suboptimal risk factors. Findings During 26·6 million person-years at risk (mean follow-up 13·3 years SD 6·4 years), 310 277 participants died. HR for the 25 × 25 risk factors and mortality varied between 1·04 (95% CI 0·98–1·11) for obesity in men and 2 ·17 (2·06–2·29) for current smoking in men. Participants with low socioeconomic status had greater mortality compared with those with high socioeconomic status (HR 1·42, 95% CI 1·38–1·45 for men; 1·34, 1·28–1·39 for women); this association remained significant in mutually adjusted models that included the 25 × 25 factors (HR 1·26, 1·21–1·32, men and women combined). The population attributable fraction was highest for smoking, followed by physical inactivity then s ocioeconomic status. Low socioeconomic status was associated with a 2·1-year reduction in life expectancy between ages 40 and 85 years, the corresponding years-of-life-lost were 0·5 years for high alcohol intake, 0·7 years for obesity, 3·9 years for diabetes, 1·6 years for hypertension, 2·4 years for physical inactivity, and 4·8 years for current smoking. Interpretation Socioeconomic circumstances, in addition to the 25 × 25 factors, should be targeted by local and global health strategies and health risk surveillance to reduce mortality. Funding European Commission, Swiss State Secretariat for Education, Swiss National Science Foundation, the Medical Research Council, NordForsk, Portuguese Foundation for Science and Technology.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
B-cell lymphomas are a diverse group of hematological neoplasms with differential etiology and clinical trajectories. Increased insights in the etiology and the discovery of prediagnostic markers ...have the potential to improve the clinical course of these neoplasms.
We investigated in a prospective study global gene expression in peripheral blood mononuclear cells of 263 incident B-cell lymphoma cases, diagnosed between 1 and 17 years after blood sample collection, and 439 controls, nested within two European cohorts.
Our analyses identified only transcriptomic markers for specific lymphoma subtypes; few markers of multiple myeloma (N = 3), and 745 differentially expressed genes in relation to future risk of chronic lymphocytic leukemia (CLL). The strongest of these associations were consistently found in both cohorts and were related to (B-) cell signaling networks and immune system regulation pathways. CLL markers exhibited very high predictive abilities of disease onset even in cases diagnosed more than 10 years after blood collection.
This is the first investigation on blood cell global gene expression and future risk of B-cell lymphomas. We mainly identified genes in relation to future risk of CLL that are involved in biological pathways, which appear to be mechanistically involved in CLL pathogenesis. Many but not all of the top hits we identified have been reported previously in studies based on tumor tissues, therefore suggesting that a mixture of preclinical and early disease markers can be detected several years before CLL clinical diagnosis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
There is increasing clinical, epidemiological, and toxicological evidence linking exposure to air pollution with multiple health outcomes that lead to increased mortality and morbidity. ...Traditionally, fixed air quality monitors have been used to provide ambient air pollution measurements, but they have spatial and temporal limitations. Rapid advances in instrument miniaturisation have made novel sensing technologies more accessible but these are prone to high sensitivity and inaccuracies. To bridge the gap between fixed monitors and small sensors we have developed a Mobile Reference Station (MoRS) – a portable platform delivering high quality measurements of air pollutants using smaller, low power reference grade instruments at high time resolutions. MoRS enables the simultaneous measurement of a broad aerosol size distribution (10 nm–35 μm), gaseous pollutant concentrations (nitrogen dioxide (NO2) and ozone (O3)), environmental parameters (noise, relatively humidity (RH) and temperature) as well as collecting filter samples for laboratory analysis. The MoRS instrumentation is described and the major challenges in ensuring that high data quality standards are maintained are discussed. Laboratory and field tests were used to derive scaling factors for all the MoRSinstrumentation. Field testing of MoRS showed excellent intercomparability against reference instrumentation (R2 > 0.98) and good agreement with reference instruments in the ultrafine aerosol range, although there was an overestimation of fine particle aerosols. Measurements taken during example mainline train and London Underground (LU) journeys are displayed showing the value of the high-quality data derived from MoRS and how this can help to disentangle multiple confounding environmental pollutants and enrich epidemiological studies.
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•A mobile measurement system was built for use in confined environments.•It measured multiple air pollutants – NO2, O3, particle size, PM2.5 and PM10.•It collected PM2.5 onto multiple filters for subsequent laboratory analysis.•Co-location at reference stations showed excellent agreement.•It was tested on journeys on subway and diesel trains in the UK.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background France has the second highest number of variant Creutzfeldt–Jakob disease (vCJD) cases worldwide. Imports of bovine carcasses from the UK probably constituted the main source of exposure ...of the French population to the bovine spongiform encephalopathy (BSE) agent. Meat products consumed whilst visiting the UK have also been considered as a possible source of exposure. Methods We estimated the number of future vCJD cases in France using a simulation approach. Both the distribution of the vCJD incubation period and the age-dependent susceptibility to the BSE agent were estimated from UK data. The French epidemic was simulated by gender and birth-cohort from data on the infectivity of UK bovine tissues and simulations of the French consumption of infected beef products. We also used data on travel to the UK between 1980 and 1995. Results We predicted 33 future cases of vCJD: 12 in the 1940–69 birth-cohort and 21 in the post-1969 birth-cohort. No case was predicted in the pre-1940 cohort. Based on our model, simulated vCJD cases occurred later in the older (1940–69) than in the younger cohort (post-1969). Age at onset was stable in the post-1969 cohort and increased in the older cohort. The model predicted a small excess of male patients. No case was attributed to travels in the UK. Conclusions This modelling confirms that a large vCJD epidemic in France is very unlikely. Since France (where 60% of the total British exports of bovine carcasses were exported) has been highly exposed to the BSE agent, our results are reassuring for most countries worldwide.
Obesity has been associated with upper gastrointestinal cancers; however, there are limited prospective data on associations by subtype/subsite. Obesity can impact hormonal factors, which have been ...hypothesized to play a role in these cancers. We investigated anthropometric and reproductive factors in relation to esophageal and gastric cancer by subtype and subsite for 476,160 participants from the European Prospective Investigation into Cancer and Nutrition cohort. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox models. During a mean follow‐up of 14 years, 220 esophageal adenocarcinomas (EA), 195 esophageal squamous cell carcinomas, 243 gastric cardia (GC) and 373 gastric noncardia (GNC) cancers were diagnosed. Body mass index (BMI) was associated with EA in men (BMI ≥30 vs. 18.5–25 kg/m2: HR = 1.94, 95% CI: 1.25–3.03) and women (HR = 2.66, 95% CI: 1.15–6.19); however, adjustment for waist‐to‐hip ratio (WHR) attenuated these associations. After mutual adjustment for BMI and HC, respectively, WHR and waist circumference (WC) were associated with EA in men (HR = 3.47, 95% CI: 1.99–6.06 for WHR >0.96 vs. <0.91; HR = 2.67, 95% CI: 1.52–4.72 for WC >98 vs. <90 cm) and women (HR = 4.40, 95% CI: 1.35–14.33 for WHR >0.82 vs. <0.76; HR = 5.67, 95% CI: 1.76–18.26 for WC >84 vs. <74 cm). WHR was also positively associated with GC in women, and WC was positively associated with GC in men. Inverse associations were observed between parity and EA (HR = 0.38, 95% CI: 0.14–0.99; >2 vs. 0) and age at first pregnancy and GNC (HR = 0.54, 95% CI: 0.32–0.91; >26 vs. <22 years); whereas bilateral ovariectomy was positively associated with GNC (HR = 1.87, 95% CI: 1.04–3.36). These findings support a role for hormonal pathways in upper gastrointestinal cancers.
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Obesity can change the body's hormone balance, and encourage the onset of cancer. Here, the authors investigated the relationship between obesity, hormones, and esophageal and gastric cancers. Using data from the EPIC cohort, they obtained information about anthropometric and reproductive factors for 476,160 participants. Excess fat around the waist, they found, was associated with esophageal adenocarcinoma and gastric cardia cancer, in women and men. In women, bearing children, as well as younger age at first pregnancy, had an inverse association with certain cancers. Ovariectomy was positively associated with gastric non‐cardia cancer, suggesting involvement of hormone pathways in these malignancies.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
We investigated the metabolomic profile associated with exposure to trihalomethanes (THMs) and nitrate in drinking water and with colorectal cancer risk in 296 cases and 295 controls from the Multi ...Case-Control Spain project. Untargeted metabolomic analysis was conducted in blood samples using ultrahigh-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. A variety of univariate and multivariate association analyses were conducted after data quality control, normalization, and imputation. Linear regression and partial least-squares analyses were conducted for chloroform, brominated THMs, total THMs, and nitrate among controls and for case-control status, together with a N-integration model discriminating colorectal cancer cases from controls through interrogation of correlations between the exposure variables and the metabolomic features. Results revealed a total of 568 metabolomic features associated with at least one water contaminant or colorectal cancer. Annotated metabolites and pathway analysis suggest a number of pathways as potentially involved in the link between exposure to these water contaminants and colorectal cancer, including nicotinamide, cytochrome P-450, and tyrosine metabolism. These findings provide insights into the underlying biological mechanisms and potential biomarkers associated with water contaminant exposure and colorectal cancer risk. Further research in this area is needed to better understand the causal relationship and the public health implications.
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IJS, KILJ, NUK, PNG, UL, UM
Previous studies have explored the relationships of air pollution and metabolic profiles with lung function. However, the metabolites linking air pollution and lung function and the associated ...mechanisms have not been reviewed from a life-course perspective. Here, we provide a narrative review summarising recent evidence on the associations of metabolic profiles with air pollution exposure and lung function in children and adults. Twenty-six studies identified through a systematic PubMed search were included with 10 studies analysing air pollution-related metabolic profiles and 16 studies analysing lung function-related metabolic profiles. A wide range of metabolites were associated with short- and long-term exposure, partly overlapping with those linked to lung function in the general population and with respiratory diseases such as asthma and COPD. The existing studies show that metabolomics offers the potential to identify biomarkers linked to both environmental exposures and respiratory outcomes, but many studies suffer from small sample sizes, cross-sectional designs, a preponderance on adult lung function, heterogeneity in exposure assessment, lack of confounding control and omics integration. The ongoing EXposome Powered tools for healthy living in urbAN Settings (EXPANSE) project aims to address some of these shortcomings by combining biospecimens from large European cohorts and harmonised air pollution exposure and exposome data.
•Nitrogen dioxide air pollution is associated with adverse cardiac remodeling in patients with dilated cardiomyopathy.•Women seem to be more susceptible to these effects.•Patients with dilated ...cardiomyopathy should be aware of the link between air pollution and their cardiovascular health so that they may take steps to minimize their exposure to pollutants.
Empirical evidence suggests a strong link between exposure to air pollution and heart failure incidence, hospitalizations, and mortality, but the biological basis of this remains unclear. We sought to determine the relationship between differential air pollution levels and changes in cardiac structure and function in patients with dilated cardiomyopathy.
We undertook a prospective longitudinal observational cohort study of patients in England with dilated cardiomyopathy (enrollment 2009–2015, n = 716, 66% male, 85% Caucasian) and conducted cross sectional analysis at the time of study enrollment. Annual average air pollution exposure estimates for nitrogen dioxide (NO2) and particulate matter with diameter of 2.5 µm or less (PM2.5) at enrolment were assigned to each residential postcode (on average 12 households). The relationship between air pollution and cardiac morphology was assessed using linear regression modelling. Greater ambient exposure to NO2 was associated with higher indexed left ventricular (LV) mass (4.3 g/m2 increase per interquartile range increase in NO2, 95% confidence interval 1.9–7.0 g/m2) and lower LV ejection fraction (–1.5% decrease per interquartile range increase in NO2, 95% confidence interval –2.7% to –0.2%), independent of age, sex, socioeconomic status, and clinical covariates. The associations were robust to adjustment for smoking status and geographical clustering by postcode area. The effect of air pollution on LV mass was greatest in women. These effects were specific to NO2 exposure.
Exposure to air pollution is associated with raised LV mass and lower LV ejection fraction, with the strongest effect in women. Although epidemiological associations between air pollution and heart failure have been established and supported by preclinical studies, our findings provide novel empirical evidence of cardiac remodeling and exposure to air pollution with important clinical and public health implications.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP