Skin exposome science in practice : current evidence on hair biomonitoring and future perspectives.

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.

The exposome in practice: Design of the EXPOsOMICS project.

EXPOsOMICS is a European Union funded project that aims to develop a novel approach to the assessment of exposure to high priority environmental pollutants, by characterizing the external and the internal components of the exposome. It focuses on air and water contaminants during critical periods of life. To this end, the project centres on 1) exposure assessment at the personal and population levels within existing European short and long-term population studies, exploiting available tools and methods which have been developed for personal exposure monitoring (PEM); and 2) multiple "omic" technologies for the analysis of biological samples (internal markers of external exposures). The search for the relationships between external exposures and global profiles of molecular features in the same individuals constitutes a novel advancement towards the development of "next generation exposure assessment" for environmental chemicals and their mixtures. The linkage with disease risks opens the way to what are defined here as 'exposome-wide association studies' (EWAS).

Prediagnostic transcriptomic markers of Chronic lymphocytic leukemia reveal perturbations 10 years before diagnosis.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

[Variant Creutzfeldt-Jakob disease in France: estimating the number of cases related to travel to the United Kingdom between 1980 and 1995]. / Le nouveau variant de la maladie de Creutzfeldt-Jakob en France: estimation du nombre de cas attribuables à un séjour dans les îles britanniques entre 1980 et 1995.

BACKGROUND: The outbreak of variant Creutzfeldt-Jakob disease (vCJD) cases rose serious concerns about secondary transmission of the disease, particularly through blood transfusion. Protective measures leading to the exclusion of potentially infectious blood donors were settled: in France, donors who had stayed more than one year in the UK were excluded. In this work, which was part of a larger study aiming to estimate the French epidemic of vCJD, the number of vCJD cases who were infected during a trip to the UK was estimated. Those estimates may notably enable the assessment of such exclusion measures. METHODS: The particular age-related structure in vCJD cases is taken into account in our simulations considering birth cohorts in the population. The total French exposure is simulated assuming the main source of infection to be dietary through consumption of mechanically recovered meat (MRM) manufactured from British bovine carcasses. Then, using a "back calculation" algorithm, all infected individuals required to produce a consistent epidemic (6 vCJD cases in 2003) was simulated. This study was exclusively focused on the part of the exposure linked to trips (beef MRM consumed in the UK while traveling) and on cases resulting from this exposure. RESULTS: The influence of exposure linked to trips to the UK was greater in the youngest cohort (6.3% of the total exposure) while it only accounted for 3.3% and 1% in the 1939-69 and in the pre-1939 birth cohorts respectively. Overall, exposure resulting from trips in the UK can be neglected with regards to the exposure linked to the consumption of MRM produced in France from British bovine carcasses. Consequently, French vCJD cases that would have been infected in the UK are very unlikely to occur (median: 0 case, IC 95%: (0-2)). Nevertheless, if such cases occur, they would probably occur in subjects born after 1969 and their onset would take place before 2010. Thus, unlike the situation in BSE-free countries, the causal relationship between travel in the UK and occurrence of vCJD cases cannot be underlined in France, as trips only account for a small part of the French exposure. CONCLUSION: Since trips in the UK slightly contribute to the overall French exposure, excluding people who travelled in the UK from blood donation would not influence the risk of secondary transmission.