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41.
  • Donat-Vargas, Carolina, et al. (author)
  • Associations between repeated measure of plasma perfluoroalkyl substances and cardiometabolic risk factors
  • 2019
  • In: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 124, s. 58-65
  • Journal article (peer-reviewed)abstract
    • Background: Perfluoroalkyl substances (PFAS) are persistent synthetic chemicals that may affect components of metabolic risk through the peroxisome proliferator-activated receptor but epidemiological data remain scarce and inconsistent.Objective: To estimate associations between repeated measurements of the main PFAS in plasma and total cholesterol, triglycerides and hypertension among the control subjects from a population-based nested case-control study on diabetes type 2 in middle-aged women and men.Methods: Participants (n = 187) were free of diabetes at both baseline and follow-up visits to the Västerbotten Intervention Programme, 10 years apart: during 1990 to 2003 (baseline) and 2001 to 2013 (follow-up). Participants left blood samples, completed questionnaires on diet and lifestyle factors, and underwent medical examinations, including measurement of blood pressure. PFAS and lipids were later determined in stored plasma samples. Associations for the repeated measurements were assessed using generalized estimating equations.Results: Six PFAS exceeded the limit of quantitation. Repeated measures of PFAS in plasma, cardiometabolic risk factors and confounders, showed an average decrease of triglycerides from −0.16 mmol/l (95% confidence interval [CI]: −0.33, 0.02 for PFOA) to −0.26 mmol/l (95% CI: −0.50, −0.08 for PFOS), when comparing the highest tertile of PFAS plasma levels with the lowest. Associations based on average PFAS measurements and follow-up triglycerides revealed similar inverse associations, although attenuated. The estimates for cholesterol and hypertension were inconsistent and with few exception non-significant.Conclusions: This study found inverse associations between PFAS and triglycerides, but did not support any clear link with either cholesterol or hypertension.
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42.
  • Donat-Vargas, Carolina, et al. (author)
  • Persistent Organochlorine Pollutants in Plasma, Blood Pressure, and Hypertension in a Longitudinal Study
  • 2018
  • In: Hypertension. - 0194-911X .- 1524-4563. ; 71:6, s. 1258-1268
  • Journal article (peer-reviewed)abstract
    • Persistent organochlorine pollutants (POPs) have shown to be involved in the atherosclerotic process and to cause endothelial cell dysfunction. To assess longitudinally whether plasma concentrations of different POPs were associated with blood pressure and risk of hypertension in middle-aged women and men. Study subjects were 850 participants in the VIP (Västerbotten Intervention Programme) with 2 blood samples and blood pressure measurements, 10 years apart, during 1990 to 2003 (baseline) and during 2000 to 2013 (follow-up). Dioxin-like and nondioxin-like polychlorinated biphenyls (DL-PCBs, NDL-PCBs) and p,p'-dichlorodiphenyldichloroethylene (DDE) were measured. Associations were assessed using generalized estimating equations. At baseline sampling 49% and at follow-up 64% had hypertension. DL-PCBs and DDE, but not NDL-PCBs or hexachlorobenzene, were associated with hypertension. Only the association for DL-PCBs remained statistically significant after lipid-standardization and adjustment for body mass index and total serum lipids. The multivariable-adjusted odds ratio of hypertension based on repeated measurements were 1.52 (95% confidence interval, 1.08-2.13) for DL-PCBs (third versus first tertile of lipid-standardized POPs). In stratified adjusted analyses, odds ratio for those born after 1950 increased to 3.99 (95% confidence interval, 2.15-7.43), whereas no association was observed among those born earlier. Based on repeated measurements, the accumulated exposure to DL-PCBs and DDE, although less clear for the latter, may disrupt the normal blood pressure levels and increase the odds of hypertension. Moreover, individuals experiencing early-life POP exposure may be at elevated risk of vascular POP effects.
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43.
  • Engström, Karin, et al. (author)
  • Evaluation of the impact of genetic polymorphisms in glutathione-related genes on the association between methylmercury or n-3 polyunsaturated long chain fatty acids and risk of myocardial infarction : a case-control study
  • 2011
  • In: Environmental Health. - : BioMed Central (BMC). - 1476-069X. ; 10:33
  • Journal article (peer-reviewed)abstract
    • Background: The n-3 polyunsaturated fatty acids eicosapentaenoic acid and docosahexaenoic acid, which are present in fish, are protective against myocardial infarction. However, fish also contains methylmercury, which influences the risk of myocardial infarction, possibly by generating oxidative stress. Methylmercury is metabolized by conjugation to glutathione, which facilitates elimination. Glutathione is also an antioxidant. Individuals with certain polymorphisms in glutathione-related genes may tolerate higher exposures to methylmercury, due to faster metabolism and elimination and/or better glutathione-associated antioxidative capacity. They would thus benefit more from the protective agents in fish, such as eicosapentaenoic+docosahexaenoic acid and selenium. The objective for this study was to elucidate whether genetic polymorphisms in glutathione-related genes modify the association between eicosapentaenoic+docosahexaenoic acid or methylmercury and risk of first ever myocardial infarction. Methods: Polymorphisms in glutathione-synthesizing (glutamyl-cysteine ligase catalytic subunit, GCLC and glutamyl-cysteine ligase modifier subunit, GCLM) or glutathione-conjugating (glutathione S-transferase P, GSTP1) genes were genotyped in 1027 individuals from northern Sweden (458 cases of first-ever myocardial infarction and 569 matched controls). The impact of these polymorphisms on the association between erythrocyte-mercury (proxy for methylmercury) and risk of myocardial infarction, as well as between plasma eicosapentaenoic+docosahexaenoic acid and risk of myocardial infarction, was evaluated by conditional logistic regression. The effect of erythrocyte-selenium on risk of myocardial infarction was also taken into consideration. Results: There were no strong genetic modifying effects on the association between plasma eicosapentaenoic+docosahexaenoic acid or erythrocyte-mercury and risk of myocardial infarction risk. When eicosapentaenoic+docosahexaenoic acid or erythrocyte-mercury were divided into tertiles, individuals with GCLM-588 TT genotype displayed a lower risk relative to the CC genotype in all but one tertile; in most tertiles the odds ratio was around 0.5 for TT. However, there were few TT carriers and the results were not statistically significant. The results were similar when taking plasma eicosapentaenoic+docosahexaenoic acid, erythrocyte-selenium and erythrocyte-mercury into account simultaneously. Conclusions: No statistically significant genetic modifying effects were seen for the association between plasma eicosapentaenoic+docosahexaenoic acid or erythrocyte-mercury and risk of myocardial infarction. Still, our results indicate that the relatively rare GCLM-588 TT genotype may have an impact, but a larger study is necessary for confirmation.
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44.
  • Gasull, Magda, et al. (author)
  • Methodological issues in a prospective study on plasma concentrations of persistent organic pollutants and pancreatic cancer risk within the EPIC cohort
  • 2019
  • In: Environmental Research. - : Elsevier. - 0013-9351 .- 1096-0953. ; 169, s. 417-433
  • Journal article (peer-reviewed)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.
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45.
  • Gaudet, Mia M, et al. (author)
  • Blood Levels of Cadmium and Lead in Relation to Breast Cancer Risk in Three Prospective Cohorts.
  • 2019
  • In: International Journal of Cancer. - : Wiley-Blackwell. - 0020-7136 .- 1097-0215. ; 144:5, s. 1010-1016
  • Journal article (peer-reviewed)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. 
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46.
  • Glynn, Anders, et al. (author)
  • Regional differences in levels of chlorinated and brominated pollutants in mother's milk from primiparous women in Sweden.
  • 2011
  • In: Environment international. - : Elsevier BV. - 1873-6750 .- 0160-4120. ; 37:1, s. 71-9
  • Journal article (peer-reviewed)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.
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47.
  • Hosnijeh, Fatemeh Saberi, et al. (author)
  • Soluble B-cell activation marker of sCD27 and sCD30 and future risk of B-cell lymphomas : a nested case-control study and meta-analyses
  • 2016
  • In: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 138:10, s. 2357-2367
  • Journal article (peer-reviewed)abstract
    • Pre-diagnostic serum/plasma concentrations of B-cell activation markers have been associated with future risk of B-cell lymphomas (BCL) in HIV-infected patients and in the general population. Current evidence for the general population is however limited and relies on relatively small numbers of observations, especially for specific histologies. We carried out a nested case-control study, including 218 BCL and 218 matched controls, within two prospective cohorts, to investigate the association between plasma levels of soluble (s)CD27 and sCD30 and future risk of BCL, and main histologic subtypes separately. To expand the evidence further, we performed meta-analyses of the published data on these associations from prospective studies among the general population. Our study revealed a significant relationship between sCD30 concentration and BCL risk (OR=0.86, 1.53, 1.76, for the 2(nd) -4(th) quartiles respectively, P-trend=0.01). Similar increased risks were observed for diffuse large B-cell lymphoma and follicular lymphoma. Analyses of sCD27 blood concentrations did not show significant associations with BCL, (OR=0.90, 1.26, 1.65 for the 2(nd) -4(th) quartiles, respectively, P-trend=0.17), but significant associations were observed for chronic lymphocytic leukaemia and for the group of 'other BCL' subtypes. Our findings involving sCD30 were confirmed within our meta-analyses of five prospective cohorts, while results were more heterogeneous for sCD27 with the exception of CLL which was found consistently in all studies. Data to date suggest that chronic B-cell stimulation might be an important mechanism involved in B-cell lymphomagenesis both in HIV-infected and in the general population.
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48.
  • Hruba, Frantiska, et al. (author)
  • Blood cadmium, mercury, and lead in children : An international comparison of cities in six European countries, and China, Ecuador, and Morocco
  • 2012
  • In: Environment International. - Oxford : Elsevier. - 0160-4120 .- 1873-6750. ; 41, s. 29-34
  • Journal article (peer-reviewed)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.
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49.
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50.
  • Jonsson, Håkan, et al. (author)
  • Lung cancer risk and radon exposure in a cohort of iron ore miners in Malmberget, Sweden
  • 2010
  • In: Occupational and Environmental Medicine. - : BMJ. - 1351-0711 .- 1470-7926. ; 67:8, s. 519-525
  • Journal article (peer-reviewed)abstract
    • OBJECTIVES: Lung cancer caused by radon in miners is a well-known risk. However, the risk estimates vary between studies and between mines. We have studied the dose response-relationship in a Swedish iron ore mine where two other studies have previously reached different risk estimates. As this mine has relatively low radon levels, the results are highly relevant for risk estimation in non-uranium underground mines.METHODS: A new cohort of 5486 male workers employed from 1923 to 1996 was established. Cumulative radon exposures were assessed based on a large number of measurements, including reconstructions of historical conditions. 122 lung cancer cases occurred during the follow-up period of 1958-2000.RESULTS: The average cumulative exposure in underground workers was 32 kBq year/m(3) (65 working level months (WLM)), experienced over 14.6 years. The excess RR (ERR) per kBq year/m(3) was 0.046 (95% CI 0.015 to 0.077; 0.022 ERR/WLM). Confounding by quartz may affect these results but appears to account only for 10-20% of the risk. The results for squamous cell and small cell lung cancer were 0.049 and 0.072, respectively. However, no increased risk was observed for adenocarcinoma (0.000 ERR per kBq year/m(3), 95% CI -0.017 to 0.017).CONCLUSION: Our overall risk estimate is about half of that found in the first Malmberget study but twice that found in the same cohort in the previously published pooled analysis. Radon did not increase the risk for adenocarcinoma in the lung.
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