| 1. |
- Adlard, B., et al.
(författare)
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Future directions for monitoring and human health research for the Arctic Monitoring and Assessment Programme
- 2018
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Ingår i: Global Health Action. - : Taylor & Francis. - 1654-9716 .- 1654-9880. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- For the last two and a half decades, a network of human health experts under the Arctic Monitoring and Assessment Program (AMAP) has produced several human health assessment reports. These reports have provided a base of scientific knowledge regarding environmental contaminants and their impact on human health in the Arctic. These reports provide scientific information and policy-relevant recommendations to Arctic governments. They also support international agreements such as the Stockholm Convention on Persistent Organic Pollutants (POPs) and the Minamata Convention on Mercury. Key topics discussed in this paper regarding future human health research in the circumpolar Arctic are continued contaminant biomonitoring, health effects research and risk communication. The objective of this paper is to describe knowledge gaps and future priorities for these fields.
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| 2. |
- Bergdahl, Ingvar A., et al.
(författare)
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Non-renal effects and the risk assessment of environmental cadmium exposure.
- 2014
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Ingår i: Environmental health perspectives. - : Environmental Health Perspectives. - 1552-9924 .- 0091-6765. ; 122:5, s. 431-8
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Tidskriftsartikel (refereegranskat)abstract
- Exposure to cadmium (Cd) has long been recognized as a health hazard, both in industry and in general populations with high exposure. Under the currently prevailing health risk assessment, the relationship between urinary Cd (U-Cd) concentrations and tubular proteinuria is used. However, doubts have recently been raised regarding the justification of basing the risk assessment on this relationship at very low exposure.
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| 3. |
- Chatziioannou, Aristotelis, et al.
(författare)
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Blood-based omic profiling supports female susceptibility to tobacco smoke-induced cardiovascular diseases
- 2017
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- We recently reported that differential gene expression and DNA methylation profiles in blood leukocytes of apparently healthy smokers predicts with remarkable efficiency diseases and conditions known to be causally associated with smoking, suggesting that blood-based omic profiling of human populations may be useful for linking environmental exposures to potential health effects. Here we report on the sex-specific effects of tobacco smoking on transcriptomic and epigenetic features derived from genome-wide profiling in white blood cells, identifying 26 expression probes and 92 CpG sites, almost all of which are affected only in female smokers. Strikingly, these features relate to numerous genes with a key role in the pathogenesis of cardiovascular disease, especially thrombin signaling, including the thrombin receptors on platelets F2R (coagulation factor II (thrombin) receptor; PAR1) and GP5 (glycoprotein 5), as well as HMOX1 (haem oxygenase 1) and BCL2L1 (BCL2-like 1) which are involved in protection against oxidative stress and apoptosis, respectively. These results are in concordance with epidemiological evidence of higher female susceptibility to tobacco-induced cardiovascular disease and underline the potential of blood-based omic profiling in hazard and risk assessment.
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| 4. |
- Hebels, Dennie G. A. J., et al.
(författare)
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Performance in omics analyses of blood samples in long-term storage : opportunities for the exploitation of existing biobanks in environmental health research
- 2013
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Ingår i: Journal of Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 121:4, s. 480-487
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Tidskriftsartikel (refereegranskat)abstract
- Background: The suitability for omic analysis of biosamples collected in previous decades and currently stored in biobanks is unknown.Objectives: We evaluated the influence of handling and storage conditions of blood-derived biosamples on transcriptomic, epigenomic (CpG methylation), plasma metabolomic [UPLC-ToFMS (ultra performance liquid chromatography-time-of-flight mass spectrometry)], and wide-target proteomic profiles.Methods: We collected fresh blood samples without RNA preservative in heparin, EDTA, or citrate and held them at room temperature for ≤ 24 hr before fractionating them into buffy coat, erythrocytes, and plasma and freezing the fractions at -80oC or in liquid nitrogen. We developed methodology for isolating RNA from the buffy coats and conducted omic analyses. Finally, we analyzed analogous samples from the EPIC-Italy and Northern Sweden Health and Disease Study biobanks.Results: Microarray-quality RNA could be isolated from buffy coats (including most biobank samples) that had been frozen within 8 hr of blood collection by thawing the samples in RNA preservative. Different anticoagulants influenced the metabolomic, proteomic, and to a lesser extent transcriptomic profiles. Transcriptomic profiles were most affected by the delay (as little as 2 hr) before blood fractionation, whereas storage temperature had minimal impact. Effects on metabolomic and proteomic profiles were noted in samples processed ≥ 8 hr after collection, but no effects were due to storage temperature. None of the variables examined significantly influenced the epigenomic profiles. No systematic influence of time-in-storage was observed in samples stored over a period of 13-17 years.Conclusions: Most samples currently stored in biobanks are amenable to meaningful omics analysis, provided that they satisfy collection and storage criteria defined in this study.
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| 5. |
- Mostafavi, Nahid, et al.
(författare)
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Associations between genome-wide gene expression and ambient nitrogen oxides (NOx)
- 2017
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Ingår i: Epidemiology. - : Lippincott Williams & Wilkins. - 1044-3983 .- 1531-5487. ; 28:3, s. 320-328
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We hypothesize that biological perturbations due to exposure to ambient air pollution are reflected in gene-expression levels in peripheral blood mononuclear cells.METHODS: We assessed the association between exposure to ambient air pollution and genome-wide gene-expression levels in peripheral blood mononuclear cells collected from 550 healthy subjects participating in cohorts from Italy and Sweden. Annual air pollution estimates of nitrogen oxides (NOx) at time of blood collection (1990 to 2006) were available from the ESCAPE study. In addition to univariate analysis and two variable selection methods to investigate the association between expression and exposure to NOx, we applied gene set enrichment analysis to assess overlap between our most perturbed genes and gene sets hypothesized to be related to air pollution and cigarette smoking. Finally, we assessed associations between NOx and CpG island methylation at the identified genes.RESULTS: Annual average NOx exposure in the Italian and Swedish cohorts was 94.2 µg/m3, and 6.7 µg/m3, respectively. Long-term exposure to NOx was associated with seven probes in the Italian cohort and one probe in the Swedish (and combined) cohorts. For genes AHCYL2 and MTMR2 changes were also seen in the methylome. Genes hypothesized to be downregulated due to cigarette smoking were enriched among the most strongly downregulated genes from our study.CONCLUSION: This study provides evidence of subtle changes in gene expression related to exposure to long-term NOx. On a global level the observed changes in the transcriptome may indicate similarities between air pollution and tobacco induced changes in the transcriptome.
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| 6. |
- Vlaanderen, Jelle, et al.
(författare)
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Exploring the nature of prediagnostic blood transcriptome markers of chronic lymphocytic leukemia by assessing their overlap with the transcriptome at the clinical stage
- 2017
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Ingår i: BMC Genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 18
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Tidskriftsartikel (refereegranskat)abstract
- Background: We recently identified 700 genes whose expression levels were predictive of chronic lymphocytic leukemia (CLL) in a genome-wide gene expression analysis of prediagnostic blood from future cases and matched controls. We hypothesized that a large fraction of these markers were likely related to early disease manifestations. Here we aim to gain a better understanding of the natural history of the identified markers by comparing results from our prediagnostic analysis, the only prediagnostic analysis to date, to results obtained from a meta-analysis of a series of publically available transcriptomics profiles obtained in incident CLL cases and controls.Results: We observed considerable overlap between the results from our prediagnostic study and the clinical CLL signals (p-value for overlap Bonferroni significant markers 0.01; p-value for overlap nominal significant markers < 2.20e-16). We observed similar patterns with time to diagnosis and similar functional annotations for the markers that were identified in both settings compared to the markers that were only identified in the prediagnostic study. These results suggest that both gene sets operate in similar pathways.Conclusion: An overlap exists between expression levels of genes predictive of CLL identified in prediagnostic blood and expression levels of genes associated to CLL at the clinical stage. Our analysis provides insight in a set of genes for which expression levels can be used to follow the time-course of the disease; providing an opportunity to study CLL progression in more detail in future studies.
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| 7. |
- Adlard, Bryan, et al.
(författare)
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MercuNorth–monitoring mercury in pregnant women from the Arctic as a baseline to assess the effectiveness of the Minamata Convention
- 2021
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Ingår i: International Journal of Circumpolar Health. - : Taylor & Francis. - 1239-9736 .- 2242-3982. ; 80:1
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Tidskriftsartikel (refereegranskat)abstract
- Exposure to mercury (Hg) is a global concern, particularly among Arctic populations that rely on the consumption of marine mammals and fish which are the main route of Hg exposure for Arctic populations.The MercuNorth project was created to establish baseline Hg levels across several Arctic regions during the period preceding the Minamata Convention. Blood samples were collected from 669 pregnant women, aged 18–44 years, between 2010 and 2016 from sites across the circumpolar Arctic including Alaska (USA), Nunavik (Canada), Greenland, Iceland, Norway, Sweden, Northern Lapland (Finland) and Murmansk Oblast (Russia). Descriptive statistics were calculated, multiple pairwise comparisons were made between regions, and unadjusted linear trend analyses were performed.Geometric mean concentrations of total Hg were highest in Nunavik (5.20 µg/L) and Greenland (3.79 µg/L), followed by Alaska (2.13 µg/L), with much lower concentrations observed in the other regions (ranged between 0.48 and 1.29 µg/L). In Nunavik, Alaska and Greenland, blood Hg concentrations have decreased significantly since 1992, 2000 and 2010 respectively with % annual decreases of 4.7%, 7.5% and 2.7%, respectively.These circumpolar data combined with fish and marine mammal consumption data can be used for assessing long-term Hg trends and the effectiveness of the Minamata Convention.
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| 8. |
- Berger, Eloise, et al.
(författare)
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Association between low-grade inflammation and Breast cancer and B-cell Myeloma and Non-Hodgkin Lymphoma : Findings from two prospective cohorts
- 2018
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Chronic inflammation may be involved in cancer development and progression. Using 28 inflammatory-related proteins collected from prospective blood samples from two case-control studies nested in the Italian component of the European Prospective Investigation into Cancer and nutrition (n = 261) and in the Northern Sweden Health and Disease Study (n = 402), we tested the hypothesis that an inflammatory score is associated with breast cancer (BC) and Β-cell Non-Hodgkin Lymphoma (B-cell NHL, including 68 multiple myeloma cases) onset. We modelled the relationship between this inflammatory score and the two cancers studied: (BC and B-cell NHL) using generalised linear models, and assessed, through adjustments the role of behaviours and lifestyle factors. Analyses were performed by cancer types pooling both populations, and stratified by cohorts, and time to diagnosis. Our results suggested a lower inflammatory score in B-cell NHL cases (β = -1.28, p = 0.012), and, to lesser, extent with BC (β = -0.96, p = 0.33) compared to controls, mainly driven by cancer cases diagnosed less than 6 years after enrolment. These associations were not affected by subsequent adjustments for potential intermediate confounders, notably behaviours. Sensitivity analyses indicated that our findings were not affected by the way the inflammatory score was calculated. These observations call for further studies involving larger populations, larger variety of cancer types and repeated measures of larger panel of inflammatory markers.
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| 9. |
- Campanella, Gianluca, et al.
(författare)
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Epigenome-wide association study of adiposity and future risk of obesity-related diseases
- 2018
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Ingår i: International Journal of Obesity. - : Nature Publishing Group. - 0307-0565 .- 1476-5497. ; 42:12, s. 2022-2035
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Tidskriftsartikel (refereegranskat)abstract
- Background: Obesity is an established risk factor for several common chronic diseases such as breast and colorectal cancer, metabolic and cardiovascular diseases; however, the biological basis for these relationships is not fully understood. To explore the association of obesity with these conditions, we investigated peripheral blood leucocyte (PBL) DNA methylation markers for adiposity and their contribution to risk of incident breast and colorectal cancer and myocardial infarction.Methods: DNA methylation profiles (Illumina Infinium® HumanMethylation450 BeadChip) from 1941 individuals from four population-based European cohorts were analysed in relation to body mass index, waist circumference, waist-hip and waistheight ratio within a meta-analytical framework. In a subset of these individuals, data on genome-wide gene expression level, biomarkers of glucose and lipid metabolism were also available. Validation of methylation markers associated with all adiposity measures was performed in 358 individuals. Finally, we investigated the association of obesity-related methylation marks with breast, colorectal cancer and myocardial infarction within relevant subsets of the discovery population.Results: We identified 40 CpG loci with methylation levels associated with at least one adiposity measure. Of these, one CpG locus (cg06500161) in ABCG1 was associated with all four adiposity measures (P=9.07×10−8 to 3.27×10−18) and lower transcriptional activity of the full-length isoform of ABCG1 (P=6.00×10−7), higher triglyceride levels (P=5.37×10−9) and higher triglycerides-to-HDL cholesterol ratio (P=1.03×10−10). Of the 40 informative and obesity-related CpG loci, two (in IL2RB and FGF18) were significantly associated with colorectal cancer (inversely, P<1.6×10−3) and one intergenic locus on chromosome 1 was inversely associated with myocardial infarction (P<1.25×10−3), independently of obesity and established risk factors.Conclusion: Our results suggest that epigenetic changes, in particular altered DNA methylation patterns, may be an intermediate biomarker at the intersection of obesity and obesity-related diseases, and could offer clues as to underlying biological mechanisms.
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| 10. |
- Chadeau-Hyam, M., et al.
(författare)
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Prediagnostic transcriptomic markers of Chronic lymphocytic leukemia reveal perturbations 10 years before diagnosis
- 2014
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 25:5, s. 1065-1072
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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