Lifetime occupational exposure to metals and welding fumes, and risk of glioma: a 7-country population-based case–control study

Background: Brain tumor etiology is poorly understood. Based on their ability to pass through the blood–brain barrier, it has been hypothesized that exposure to metals may increase the risk of brain cancer. Results from the few epidemiological studies on this issue are limited and inconsistent. Methods: We investigated the relationship between glioma risk and occupational exposure to five metals - lead, cadmium, nickel, chromium and iron- as well as to welding fumes, using data from the seven-country INTEROCC study. A total of 1800 incident glioma cases and 5160 controls aged 30–69 years were included in the analysis. Lifetime occupational exposure to the agents was assessed using the INTEROCC JEM, a modified version of the Finnish job exposure matrix FINJEM. Results: In general, cases had a slightly higher prevalence of exposure to the various metals and welding fumes than did controls, with the prevalence among ever exposed ranging between 1.7 and 2.2% for cadmium to 10.2 and 13.6% for iron among controls and cases, respectively. However, in multivariable logistic regression analyses, there was no association between ever exposure to any of the agents and risk of glioma with odds ratios (95% confidence intervals) ranging from 0.8 (0.7–1.0) for lead to 1.1 (0.7–1.6) for cadmium. Results were consistent across models considering cumulative exposure or duration, as well as in all sensitivity analyses conducted. Conclusions: Findings from this large-scale international study provide no evidence for an association between occupational exposure to any of the metals under scrutiny or welding fumes, and risk of glioma

INTEROCC case–control study: lack of association between glioma tumors and occupational exposure to selected combustion products, dusts and other chemical agents

Background: The aim was to investigate possible associations between glioma (an aggressive type of brain cancer) and occupational exposure to selected agents: combustion products (diesel and gasoline exhaust emissions, benzo (a) pyrene), dusts (animal dust, asbestos, crystalline silica, wood dust) and some other chemical agents (formaldehyde, oil mist, sulphur dioxide). Methods: The INTEROCC study included cases diagnosed with glioma during 2000-2004 in sub-regions of seven countries. Population controls, selected from various sampling frames in different centers, were frequency or individually matched to cases by sex, age and center. Face-to-face interviews with the subject or a proxy respondent were conducted by trained interviewers. Detailed information was collected on socio-economic and lifestyle characteristics, medical history and work history. Occupational exposure to the 10 selected agents was assessed by a job exposure matrix (JEM) which provides estimates of the probability and level of exposure for different occupations. Using a 25% probability of exposure in a given occupation in the JEM as the threshold for considering a worker exposed, the lifetime prevalence of exposure varied from about 1% to about 15% for the different agents. Associations between glioma and each of the 10 agents were estimated by conditional logistic regression, and using three separate exposure indices: i) ever vs. never; ii) lifetime cumulative exposure; iii) total duration of exposure. Results: The study sample consisted of 1,800 glioma cases and 5,160 controls. Most odds ratio estimates were close to the null value. None of the ten agents displayed a significantly increased odds ratio nor any indication of dose-response relationships with cumulative exposure or with duration of exposure. Conclusion: Thus, there was no evidence that these exposures influence risk of glioma.This is the publisher’s final pdf. The published article is copyrighted by BioMed Central Ltd. and can be found at: http://www.biomedcentral.com/Keywords: Brain cancer, Case-control study, International, Job exposure matrix, Risk facto

Occupational exposure to extremely low frequency magnetic fields and brain tumour risks in the INTEROCC study

BACKGROUND: Occupational exposure to extremely low frequency magnetic fields (ELF) is a suspected risk factor for brain tumours, however the literature is inconsistent. Few studies have assessed whether ELF in different time windows of exposure may be associated with specific histologic types of brain tumours. This study examines the association between ELF and brain tumours in the large-scale INTEROCC study. METHODS: Cases of adult primary glioma and meningioma were recruited in seven countries (Australia, Canada, France, Germany, Israel, New Zealand, United Kingdom) between 2000 and 2004. Estimates of mean workday ELF exposure based on a job exposure matrix assigned. Estimates of cumulative exposure, average exposure, maximum exposure, and exposure duration were calculated for the lifetime, and 1-4, 5-9, and 10+ years prior to the diagnosis/reference date. RESULTS: There were 3,761 included brain tumour cases (1,939 glioma, 1,822 meningioma) and 5,404 population controls. There was no association between lifetime cumulative ELF exposure and glioma or meningioma risk. However, there were positive associations between cumulative ELF 1-4 years prior to the diagnosis/reference date and glioma (odds ratio (OR) ≥ 90th percentile vs < 25th percentile = 1.67, 95% confidence interval (CI) 1.36-2.07, p < 0.0001 linear trend), and, somewhat weaker associations with meningioma (OR ≥ 90th percentile vs < 25th percentile = 1.23, 95% CI 0.97-1.57, p = 0.02 linear trend). CONCLUSIONS: Results showed positive associations between ELF in the recent past and glioma. IMPACT: Occupational ELF exposure may play a role in the later stages (promotion and progression) of brain tumourigenesis.Keywords: glioma, meningioma, occupation, case control study, extremely low frequency magnetic field

A Solve-RD ClinVar-based reanalysis of 1522 index cases from ERN-ITHACA reveals common pitfalls and misinterpretations in exome sequencing

Purpose Within the Solve-RD project (https://solve-rd.eu/), the European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies aimed to investigate whether a reanalysis of exomes from unsolved cases based on ClinVar annotations could establish additional diagnoses. We present the results of the “ClinVar low-hanging fruit” reanalysis, reasons for the failure of previous analyses, and lessons learned. Methods Data from the first 3576 exomes (1522 probands and 2054 relatives) collected from European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies was reanalyzed by the Solve-RD consortium by evaluating for the presence of single-nucleotide variant, and small insertions and deletions already reported as (likely) pathogenic in ClinVar. Variants were filtered according to frequency, genotype, and mode of inheritance and reinterpreted. Results We identified causal variants in 59 cases (3.9%), 50 of them also raised by other approaches and 9 leading to new diagnoses, highlighting interpretation challenges: variants in genes not known to be involved in human disease at the time of the first analysis, misleading genotypes, or variants undetected by local pipelines (variants in off-target regions, low quality filters, low allelic balance, or high frequency). Conclusion The “ClinVar low-hanging fruit” analysis represents an effective, fast, and easy approach to recover causal variants from exome sequencing data, herewith contributing to the reduction of the diagnostic deadlock

Pierre Valentin Boudhors, initiateur du néo-classicisme à Strasbourg

Parent Brigitte. Pierre Valentin Boudhors, initiateur du néo-classicisme à Strasbourg. In: Bulletin Monumental, tome 175, n°2, année 2017. p. 172

Partenariat pour le changement et l'innovation pédagogique en vue d'améliorer les soins de santé primaires :exemple d'un projet de développement avec les pays du Sud

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