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  • Gasull, Magda, et al. (författare)
  • Methodological issues in a prospective study on plasma concentrations of persistent organic pollutants and pancreatic cancer risk within the EPIC cohort
  • 2019
  • Ingår i: Environmental Research. - : Elsevier. - 0013-9351 .- 1096-0953. ; 169, s. 417-433
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The use of biomarkers of environmental exposure to explore new risk factors for pancreatic cancer presents clinical, logistic, and methodological challenges that are also relevant in research on other complex diseases.OBJECTIVES: First, to summarize the main design features of a prospective case-control study -nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort- on plasma concentrations of persistent organic pollutants (POPs) and pancreatic cancer risk. And second, to assess the main methodological challenges posed by associations among characteristics and habits of study participants, fasting status, time from blood draw to cancer diagnosis, disease progression bias, basis of cancer diagnosis, and plasma concentrations of lipids and POPs. Results from etiologic analyses on POPs and pancreatic cancer risk, and other analyses, will be reported in future articles.METHODS: Study subjects were 1533 participants (513 cases and 1020 controls matched by study centre, sex, age at blood collection, date and time of blood collection, and fasting status) enrolled between 1992 and 2000. Plasma concentrations of 22 POPs were measured by gas chromatography - triple quadrupole mass spectrometry (GC-MS/MS). To estimate the magnitude of the associations we calculated multivariate-adjusted odds ratios by unconditional logistic regression, and adjusted geometric means by General Linear Regression Models.RESULTS: There were differences among countries in subjects' characteristics (as age, gender, smoking, lipid and POP concentrations), and in study characteristics (as time from blood collection to index date, year of last follow-up, length of follow-up, basis of cancer diagnosis, and fasting status). Adjusting for centre and time of blood collection, no factors were significantly associated with fasting status. Plasma concentrations of lipids were related to age, body mass index, fasting, country, and smoking. We detected and quantified 16 of the 22 POPs in more than 90% of individuals. All 22 POPs were detected in some participants, and the smallest number of POPs detected in one person was 15 (median, 19) with few differences by country. The highest concentrations were found for p,p'-DDE, PCBs 153 and 180 (median concentration: 3371, 1023, and 810 pg/mL, respectively). We assessed the possible occurrence of disease progression bias (DPB) in eight situations defined by lipid and POP measurements, on one hand, and by four factors: interval from blood draw to index date, tumour subsite, tumour stage, and grade of differentiation, on the other. In seven of the eight situations results supported the absence of DPB.CONCLUSIONS: The coexistence of differences across study centres in some design features and participant characteristics is of relevance to other multicentre studies. Relationships among subjects' characteristics and among such characteristics and design features may play important roles in the forthcoming analyses on the association between plasma concentrations of POPs and pancreatic cancer risk.
  • Ek, Weronica E., et al. (författare)
  • Tea and coffee consumption in relation to DNA methylation in four European cohorts
  • 2017
  • Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 26:16, s. 3221-3231
  • Tidskriftsartikel (refereegranskat)abstract
    • Lifestyle factors, such as food choices and exposure to chemicals, can alter DNA methylation and lead to changes in gene activity. Two such exposures with pharmacologically active components are coffee and tea consumption. Both coffee and tea has been suggested to play an important role in modulating disease-risk in humans by suppressing tumour progression, decreasing inflammation and influencing estrogen metabolism. These mechanisms may be mediated by changes in DNA methylation.To investigate if DNA methylation in blood is associated with coffee and tea consumption we performed a genome-wide DNA methylation study for coffee and tea consumption in four European cohorts (N = 3,096). DNA methylation was measured from whole blood at 421,695 CpG sites distributed throughout the genome and analysed in men and women both separately and together in each cohort. Meta-analyses of the results and additional regional-level analyses were performed.After adjusting for multiple testing, the meta-analysis revealed that two individual CpG-sites, mapping to DNAJC16 and TTC17, were differentially methylated in relation to tea consumption in women. No individual sites were associated in men or in the sex-combined analysis for tea or coffee. The regional analysis revealed that 28 regions were differentially methylated in relation to tea consumption in women. These regions contained genes known to interact with estradiol metabolism and cancer. No significant regions were found in the sex-combined and male-only analysis for either tea or coffee consumption.
  • Chatziioannou, Aristotelis, et al. (författare)
  • Blood-based omic profiling supports female susceptibility to tobacco smoke-induced cardiovascular diseases
  • 2017
  • Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 7
  • 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.
  • de Mello, Vanessa D., et al. (författare)
  • Indolepropionic acid and novel lipid metabolites are associated with a lower risk of type 2 diabetes in the Finnish Diabetes Prevention Study
  • 2017
  • Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322 .- 2045-2322. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • Wide-scale profiling technologies including metabolomics broaden the possibility of novel discoveries related to the pathogenesis of type 2 diabetes (T2D). By applying non-targeted metabolomics approach, we investigated here whether serum metabolite profile predicts T2D in a well-characterized study population with impaired glucose tolerance by examining two groups of individuals who took part in the Finnish Diabetes Prevention Study (DPS); those who either early developed T2D (n = 96) or did not convert to T2D within the 15-year follow-up (n = 104). Several novel metabolites were associated with lower likelihood of developing T2D, including indole and lipid related metabolites. Higher indolepropionic acid was associated with reduced likelihood of T2D in the DPS. Interestingly, in those who remained free of T2D, indolepropionic acid and various lipid species were associated with better insulin secretion and sensitivity, respectively. Furthermore, these metabolites were negatively correlated with low-grade inflammation. We replicated the association between indolepropionic acid and T2D risk in one Finnish and one Swedish population. We suggest that indolepropionic acid, a gut microbiota-produced metabolite, is a potential biomarker for the development of T2D that may mediate its protective effect by preservation of alpha-cell function. Novel lipid metabolites associated with T2D may exert their effects partly through enhancing insulin sensitivity.
  • Glynn, Anders, et al. (författare)
  • Regional differences in levels of chlorinated and brominated pollutants in mother's milk from primiparous women in Sweden.
  • 2011
  • Ingår i: Environment international. - : Elsevier. - 1873-6750 .- 0160-4120. ; 37:1, s. 71-9
  • Tidskriftsartikel (refereegranskat)abstract
    • Early life exposure to halogenated persistent organic pollutants, such as polychlorinated biphenyls (PCBs), the DDT metabolite p,p'-dichlorodiphenyldichloroethane (p,p'-DDE), polybrominated diphenylethers (PBDEs), and hexabromocyclododecane (HBCD), may affect human health. We determined if there are regional differences in mother's milk levels of these compounds in Sweden. In year 2000-2004, milk was sampled from 204 randomly recruited primiparas from four regions of Sweden. Levels of the compounds were measured by gas chromatography with dual electron-capture detectors. Women were recruited at delivery in three hospitals located in urban areas in southern and central Sweden (Lund, Gothenburg and Uppsala), and in one hospital located in a more rural area in northern Sweden (Lycksele). Information about dietary habits and medical/life-style factors were collected by questionnaires. Among PCB congeners, CB 153, CB 138 and CB 180 showed the highest median concentrations (18-48 ng/g mother's milk lipid), whereas more than 50% of the women had CB 52, CB 101, CB 114, and CB 157 levels below the LOQ (0.3-1.5 ng/g lipid). Median p,p'-DDE levels were in the range of 46-78 ng/g lipid. BDE 47 showed the highest median concentrations (1-2 ng/g lipid) among the brominated compounds, whereas more than 50% of the women had levels of BDE 28, BDE 66, BDE 138, BDE 154, and HBCD below the LOQ (0.05-0.10 ng/g lipid). Regional differences in median organohalogen compound concentrations were small, less than 2-fold. Lycksele women generally had the lowest levels of Σmono-and Σdi-ortho PCBs, mainly due to a lower average age. In contrast, these women had higher tetra- to penta-brominated PBDE levels, but no diet or life-style factor could explain this finding. Wide ranges of PBDEs and HBCD levels (up to 200-fold) were found, especially in the Lycksele area. The highest levels of PBDE were in the range of average levels found in mother's milk from North America, suggesting that food may not be the only source of exposure to PBDEs among some individuals.
  • Åkesson, Agneta, et al. (författare)
  • Non-renal effects and the risk assessment of environmental cadmium exposure.
  • 2014
  • Ingår i: Environmental health perspectives. - : National Institute of Environmental Health Sciences. - 1552-9924 .- 0091-6765. ; 122:5, s. 431-8
  • 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.
  • Adlard, B., et al. (författare)
  • Future directions for monitoring and human health research for the Arctic Monitoring and Assessment Programme
  • 2018
  • Ingår i: Global Health Action. - : Taylor & Francis. - 1654-9716 .- 1654-9880. ; 11:1
  • 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.
  • Gaudet, Mia M., et al. (författare)
  • Blood levels of cadmium and lead in relation to breast cancer risk in three prospective cohorts
  • 2019
  • Ingår i: International Journal of Cancer. - : John Wiley and Sons. - 0020-7136 .- 1097-0215. ; 144:5, s. 1010-1016
  • Tidskriftsartikel (refereegranskat)abstract
    • Cadmium and lead have been classified as carcinogens by the International Agency for Research on Cancer. However, their associations with breast cancer risk are unknown despite their persistence in the environment and ubiquitous human exposure. We examined associations of circulating levels of cadmium and lead with breast cancer risk in three case–control studies nested within the Cancer Prevention Study-II (CPS-II) LifeLink Cohort, European Prospective Investigation into Cancer and Nutrition – Italy (EPIC-Italy) and the Northern Sweden Health and Disease Study (NSHDS) cohorts. Metal levels were measured in stored erythrocytes from 1,435 cases and 1,433 controls using inductively coupled plasma-mass spectrometry. Summary relative risks (RR) and 95% confidence intervals (CI) were calculated using random-effects models with each study result weighted by the within- and between-study variances. I2 values were calculated to estimate proportion of between study variation. Using common cut-points, cadmium levels were not associated with breast cancer risk in the CPS-II cohort (continuous RR = 1.01, 95% CI 0.76–1.34), but were inversely associated with risk in the EPIC- Italy (continuous RR = 0.80, 95% CI 0.61–1.03) and NSHDS cohorts (continuous RR = 0.73, 95% CI 0.54–0.97). The inverse association was also evident in the meta-analysis (continuous RR = 0.84, 95% CI 0.69–1.01) with low between-study heterogeneity. Large differences in lead level distributions precluded a meta-analysis of their association with breast cancer risk; no associations were found in the three studies. Adult cadmium and lead levels were not associated with higher risk of breast cancer in our large meta-analysis.
  • Hruba, Frantiska, et al. (författare)
  • Blood cadmium, mercury, and lead in children : An international comparison of cities in six European countries, and China, Ecuador, and Morocco
  • 2012
  • Ingår i: Environment International. - Oxford : Elsevier. - 0160-4120 .- 1873-6750. ; 41, s. 29-34
  • Tidskriftsartikel (refereegranskat)abstract
    • Children's blood-lead concentration (B-Pb) is well studied, but little is known about cadmium (B-Cd) and mercury (B-Hg), in particular for central Europe. Such information is necessary for risk assessment and management. Therefore, we here describe and compare B-Pb, B-Cd and B-Hg in children in six European, and three non-European cities, and identify determinants of these exposures. About 50 school children (7-14 years) from each city were recruited (totally 433) in 2007-2008. Interview and questionnaire data were obtained. A blood sample was analyzed: only two laboratories with strict quality control were used. The European cities showed only minor differences for B-Cd (geometric means 0.11-0.17 mu g/L) and B-Pb (14-20 mu g/L), but larger for B-Hg (0.12-0.94 mu g/L). Corresponding means for the non-European countries were 0.21-0.26, 32-71, and 0.3-3.2 mu g/L, respectively. For B-Cd in European samples, traffic intensity close to home was a statistically significant determinant, for B-Hg fish consumption and amalgam fillings, and for B-Pb sex (boys higher). This study shows that European city children's B-Cd and B-Pb vary only little between countries; B-Hg differs considerably, due to varying tooth restoration practices and fish intake. Traffic intensity seemed to be a determinant for B-Cd. The metal concentrations were low from a risk perspective but the chosen non-European cities showed higher concentrations than the cities in Europe. (C) 2011 Elsevier Ltd. All rights reserved.
  • Schillemans, Tessa, et al. (författare)
  • Plasma metabolites associated with exposure to perfluoroalkyl substances and risk of type 2 diabetes – A nested case-control study
  • 2021
  • Ingår i: Environment International. - 0160-4120 .- 1873-6750. ; 146
  • Tidskriftsartikel (refereegranskat)abstract
    • Perfluoroalkyl substances (PFAS) are widespread persistent environmental pollutants. There is evidence that PFAS induce metabolic perturbations in humans, but underlying mechanisms are still unknown. In this exploratory study, we investigated PFAS-related plasma metabolites for their associations with type 2 diabetes (T2D) to gain potential mechanistic insight in these perturbations. We used untargeted LC-MS metabolomics to find metabolites related to PFAS exposures in a case-control study on T2D (n = 187 matched pairs) nested within the Västerbotten Intervention Programme cohort. Following principal component analysis (PCA), six PFAS measured in plasma appeared in two groups: 1) perfluorononanoic acid, perfluorodecanoic acid and perfluoroundecanoic acid and 2) perfluorohexane sulfonic acid, perfluorooctane sulfonic acid and perfluorooctanoic acid. Using a random forest algorithm, we discovered metabolite features associated with individual PFAS and PFAS exposure groups which were subsequently investigated for associations with risk of T2D. PFAS levels correlated with 171 metabolite features (0.16 ≤ |r| ≤ 0.37, false discovery rate (FDR) adjusted p < 0.05). Out of these, 35 associated with T2D (p < 0.05), with 7 remaining after multiple testing adjustment (FDR < 0.05). PCA of the 35 PFAS- and T2D-related metabolite features revealed two patterns, dominated by glycerophospholipids and diacylglycerols, with opposite T2D associations. The glycerophospholipids correlated positively with PFAS and associated inversely with risk for T2D (Odds Ratio (OR) per 1 standard deviation (1-SD) increase in metabolite PCA pattern score = 0.2; 95% Confidence Interval (CI) = 0.1–0.4). The diacylglycerols also correlated positively with PFAS, but they associated with increased risk for T2D (OR per 1-SD = 1.9; 95% CI = 1.3–2.7). These results suggest that PFAS associate with two groups of lipid species with opposite relations to T2D risk.
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