| 11. |
- Engström, Karin, et al.
(författare)
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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
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Ingår i: Environmental Health. - : BioMed Central (BMC). - 1476-069X. ; 10:33
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Tidskriftsartikel (refereegranskat)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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| 12. |
- Glynn, Anders, et al.
(författare)
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Regional differences in levels of chlorinated and brominated pollutants in mother's milk from primiparous women in Sweden.
- 2011
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Ingår i: Environment international. - : Elsevier BV. - 1873-6750 .- 0160-4120. ; 37:1, s. 71-9
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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.
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| 13. |
- Hruba, Frantiska, et al.
(författare)
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Blood cadmium, mercury, and lead in children : An international comparison of cities in six European countries, and China, Ecuador, and Morocco
- 2012
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Ingår i: Environment International. - Oxford : Elsevier. - 0160-4120 .- 1873-6750. ; 41, s. 29-34
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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.
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| 14. |
- Jonsson, Håkan, et al.
(författare)
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Lung cancer risk and radon exposure in a cohort of iron ore miners in Malmberget, Sweden
- 2010
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Ingår i: Occupational and Environmental Medicine. - : BMJ. - 1351-0711 .- 1470-7926. ; 67:8, s. 519-525
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Tidskriftsartikel (refereegranskat)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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| 15. |
- Liang, Yihuai, et al.
(författare)
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Renal function after reduction in cadmium exposure : an eight-year follow-up of residents in cadmium-polluted areas
- 2012
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Ingår i: Journal of Environmental Health Perspectives. - : National Institute of Environmental Health Sciences. - 0091-6765 .- 1552-9924. ; 120:2, s. 223-228
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Tidskriftsartikel (refereegranskat)abstract
- Background and objective: Long-term exposure to cadmium (Cd) causes renal dysfunction, but its change with exposure is unknown. We aimed at assessing the evolution of Cd-induced renal effects after a reduction in dietary exposure to Cd in rice.Methods: 412 residents in previously Cd-polluted and non-polluted areas were examined twice: in 1998 and 2006. Changes in blood Cd, urinary Cd, and kidney function (N-acetyl-β-D-glucosaminidase = NAG, β2-microglobulin, and albumin in urine) were measured. Results: In the most polluted area, mean blood Cd was 8.9 μg/L in 1998 and 3.3 μg/L in 2006, and urinary Cd was 11.6 and 9.0 μg/g creatinine in 1998 and 2006, respectively. Urinary albumin in 1998 increased with urinary Cd but no such exposure-response appeared for 2006 albumin versus urinary Cd 1998, indicating recovery. Other biomarkers of kidney function were also elevated in 1998. Partial recovery was observed for NAG, among women, and suggested for β2-microglobulin, among young individuals. The probability of having a β2-microglobulin above the 95th percentile in 2006 was high in those with an elevated β2-microglobulin in 1998 (odds ratio: 24.8, 95% CI: 11.2-55.3), whereas corresponding estimates for albumin and NAG were 3.0 (1.2-7.5) and 2.6 (1.6-4.4), respectively.Conclusions: Results suggest that a Cd-mediated increase in urinary albumin excretion is reversible upon substantial reduction of exposure. For the markers of tubular effects, a tendency towards improvement, but not complete recovery, was observed. Data from repeated observations suggests that β2-microglobulin may be more informative than NAG as an indicator for the individual's future tubular function.
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| 16. |
- Nilsson Sommar, Johan, et al.
(författare)
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Hip Fracture Risk and Cadmium in Erythrocytes : A Nested Case-Control Study with Prospectively Collected Samples
- 2014
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Ingår i: Calcified Tissue International. - : Springer. - 0171-967X .- 1432-0827. ; 94:2, s. 183-190
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Tidskriftsartikel (refereegranskat)abstract
- Several studies have investigated the relation between bone mass density and cadmium exposure, but only few studies have been performed on fractures and biomarkers of cadmium. This study analyzed the association between hip fracture risk and cadmium in erythrocytes (Ery-Cd). Prospective samples from the Northern Sweden Health and Disease Study's biobank were used for 109 individuals who later in life had sustained a low-trauma hip fracture, matched with two controls of the same age and gender. The mean concentration of Ery-Cd (±SD) in case samples was 1.3 ± 1.4 versus 0.9 ± 1.0 μg/L in controls. The odds ratio (OR) was 1.63 [95 % confidence interval (CI) 1.10-2.42] for suffering a hip fracture for each microgram per liter increase in Ery-Cd. However, when taking smoking into consideration (never, former, or current), neither Ery-Cd nor smoking showed a statistically significant increase in fracture risk. Using multiple conditional logistic regression with BMI, height, and smoking, the estimated OR for a 1-μg/L increase in Ery-Cd was 1.52 (95 % CI 0.77-2.97). Subgroup analysis showed an increased fracture risk among women (OR = 1.94, 95 % CI 1.18-3.20, for a 1 μg/L increase), which also remained in the multiple analysis (OR = 3.33, 95 % CI 1.29-8.56). This study shows that fracture risk is associated with Ery-Cd. It is, however, not possible to draw firm conclusions on whether cadmium is the causal factor or whether other smoking-related factors cause this association. Subgroup analysis shows that cadmium is a risk factor for hip fracture among women.
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| 17. |
- Nilsson Sommar, Johan, 1983-
(författare)
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Prospective and longitudinal human studies of lead and cadmium exposure and the kidney
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cadmium and lead accumulate in humans and can have toxic effects. Exposure to cadmium is well known to cause kidney damage. Cadmium binds to metallothioneins, proteins that play a role in cadmium transport. Lead exposure’s main effect is on the central nervous system, but associations with kidney disease have also been found, although it is unknown if the latter is a causal association. The main source of both metals within the non-smoking population is from the diet.This thesis aims to 1) compare the biomarkers lead and cadmium concentration in whole-blood, plasma and urine with regard to their ability to discriminate between individuals with different mean concentrations, and to describe the effect of urinary dilution, 2) estimate the association between end-stage renal disease and blood concentrations of cadmium, lead and mercury, using prospectively collected samples for exposure evaluation, 3) use longitudinal data on kidney function makers to evaluate kidney recovery after a substantial decrease in cadmium exposure, and 4) assess the influence of metallothionein polymorphisms (MT1A rs11076161, MT2A rs10636 and MT2A rs28366003) on cadmium-associated kidney toxicity and recovery due to a reduction in Cd exposure.Repeated sampling of whole-blood, plasma and urine was conducted on 48 occupationally lead-exposed men and 20 individuals under normal environmental lead exposure, for estimation of the day-to-day and between individual-variation. Prospective samples were obtained for 118 cases that later in life developed end-stage renal disease, and 378 matched controls. Erythrocyte cadmium, lead, and mercury concentrations were determined and the risk of developing end-stage renal disease associated with metal concentrations was estimated. For evaluation of kidney recovery after a reduction in cadmium exposure and to test for gene-environment interactions, follow-up data on N-acetyl-β‑d-glucosaminidase, β2‑microglobulin, albumin, and gene polymorphisms were obtained for 412 individuals within the Chinese population and the relation to blood and urinary cadmium was assessed.The concentration of lead in blood was found to be the biomarker with the largest fraction of the total variance attributable to between-individual variation, and was therefore the biomarker with the best ability to discriminate between individuals with different mean concentrations, both for individuals under occupational and normal environmental exposure (91 and 95%, respectively). Adjusting for urinary dilution had a great effect on the fraction of the total variance attributable to between-individual variation among individuals with normal lead exposure but only a minor effect among those who were occupationally exposed. Variance analysis showed that blood concentrations were also the best discriminating biomarker for cadmium.Erythrocyte lead was, in a univariate model, associated with an increased risk of developing end-stage renal disease [odds ratio (OR) = 1.54 for an interquartile range increase, with a 95% confidence interval (CI) = 1.18-2.00], while erythrocyte mercury was negatively associated (OR = 0.75 for an interquartile range increase, with a 95% CI = 0.56-0.99). For erythrocyte cadmium, the OR was 1.15 with a 95% CI of 0.99-1.34. Associations with lead and cadmium were only seen among men. In the study on kidney recovery, the proportion of individuals with albumin level above the 95th percentile decreased between baseline and follow up, but no decrease was found for the tubular markers N-acetyl-β‑d-glucosaminidase and β2-microglobulin. Metallothionein polymorphisms modified cadmium-associated effects on N-acetyl-β‑d-glucosaminidase and β2-microglobulin levels but did not modify cadmium-associated change in any of the kidney function markers between baseline and follow up after a substantial decrease in exposure.Blood concentrations of lead and cadmium are the biomarkers with the best ability to discriminate between individuals with different mean concentrations. Adjustment for urinary dilution has great influence on the fraction of the total variance attributed to between individual variation among urine samples with low lead concentrations, but only a small influence on samples with high lead concentrations. This suggests a difference in excretion. The association between end-stage renal disease and low-level lead exposure, as assessed through prospective erythrocyte samples, gives reason for concern, although further studies are needed to determine causality. A cadmium-associated increase in albumin is reversible after a substantial reduction in exposure, but this is not the case for the observed tubular effects. The tubular kidney effects of cadmium might be modified by the MT1A rs11076161 polymorphism.
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| 18. |
- Nordberg, Gunnar, et al.
(författare)
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Kidney dysfunction and cadmium exposure : Factors influencing dose-response relationships
- 2012
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Ingår i: Journal of Trace Elements in Medicine and Biology. - : Elsevier BV. - 0946-672X .- 1878-3252. ; 26:2-3, s. 197-200
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Tidskriftsartikel (refereegranskat)abstract
- Our early toxicological studies showed that metallothionein (MT) is a protein that carries cadmium (Cd) to the kidney, explaining why Cd exposures during long time periods may give rise to kidney dysfunction. This dysfunction is usually considered to be the critical effect, i.e. the adverse effect that occurs at the lowest exposure level. MT also provides intracellular protection against cadmium toxicity. In studies of population groups in cadmium contaminated areas in China, we investigated factors that affected the relationship between internal dose of Cd, as indicated by blood Cd (BCd) or urinary Cd (UCd), and the prevalence of kidney dysfunction. We found dose-response relationships between UCd and the prevalence of increased levels of biomarkers of renal tubular dysfunction (urinary beta-2-microglobulin, B2M, or N-acetyl-beta-D-glucosaminidase - NAG) or urinary albumin (UAlb), a biomarker of glomerular kidney dysfunction. Two years after Cd intake from contaminated rice was diminished, renal tubular dysfunction appeared unchanged or aggravated among those with higher UCd; Another 8 years later, i.e. 10 years after Cd intake was decreased, the prevalence of renal tubular dysfunction was still increased but UAlb had returned to normal. Factors that influenced the dose-response relationships were: (1) time after maximum exposure. (2) Concomitant exposure to other nephrotoxic agents such as inorganic arsenic. (3) Cd induced metallothionein mRNA levels in peripheral blood lymphocytes, used as a biomarker of the ability of each person, to synthesize MT. (4) The occurrence of increased levels in blood plasma of autoantibodies against MT. The two last points further support a role in humans of MT as a protective protein against tissue damage from cadmium and gives support to previous ideas developed partly in experimental systems.
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| 19. |
- Pawlas, Natalia, et al.
(författare)
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Cadmium, mercury and lead in the blood of urban women in Croatia, the Czech Republic, Poland, Slovakia, Slovenia, Sweden, China, Ecuador and Morocco
- 2013
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Ingår i: International Journal of Occupational Medicine and Environmental Health. - 1896-494X .- 1232-1087. ; 26:1, s. 58-72
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the study was to make an international comparison of blood levels of cadmium (B-Cd), lead (B-Pb) and mercury (B-Hg) of women in seven European, and three non-European cities, and to identify determinants. About 50 women (age: 46-62) from each city were recruited (totally 480) in 2006-2009. Interview and questionnaire data were obtained. Blood samples were analysed in one laboratory to avoid interlaboratory variation. Between the European cities, the B-Pb and B-Cd results vary little (range of geometric means: 13.5-27.0 mu g/l and 0.25-0.65 mu g/l, respectively); the variation of B-Hg was larger (0.40-1.38 mu g/l). Between the non-European cities the results for B-Pb, B-Cd and B-Hg were 19.2-68.0, 0.39-0.99 and 1.01-2.73 mu g/l, respectively. Smoking was a statistically significant determinant for B-Cd, while fish and shellfish intakes contributed to B-Hg and B-Pb, amalgam fillings also contributed to B-Hg. The present results confirm the previous results from children; the exposure to lead and cadmium varies only little between different European cities suggesting that other factors than the living area are more important. The study also confirms the previous findings of higher cadmium and lead levels in some non-European cities. The geographical variation for mercury is significant.
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| 20. |
- Sommar, Johan Nilsson, et al.
(författare)
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Investigation of lead concentrations in whole blood, plasma and urine as biomarkers for biological monitoring of lead exposure
- 2014
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Ingår i: Journal of Exposure Science & Environmental Epidemiology. - : Springer Science and Business Media LLC. - 1559-064X .- 1559-0631. ; 24:1, s. 51-57
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Tidskriftsartikel (refereegranskat)abstract
- Lead in blood is a major concept in biomonitoring of exposure but investigations of its alternatives are scarce. The aim of the study was to describe different lead biomarkers' variances, day-to-day and between individuals, estimating their fraction of the total variance. Repeated sampling of whole blood, plasma and urine were conducted for 48 lead-exposed men and 20 individuals under normal environmental lead exposure, in total 603 measurements. For lead workers, the fraction of the total variance attributed to differences between individuals was 91% for whole-blood lead (geometric mean 227 mg/l; geometric standard deviation (GSD): 1.55 mg/l); plasma 78% (0.57 mg/l; GSD: 1.84 mg/l); density-adjusted urine 82%; and unadjusted urine 75% (23.7 mg/l; GSD: 2.48 mg/l). For the individuals under normal lead exposure, the corresponding fractions were 95% of the total variance for whole blood (20.7 mg/l; GSD: 8.6 mg/l), 15% for plasma (0.09 mg/l; GSD: 0.04 mg/l), 87% for creatinine-adjusted urine and 34% for unadjusted (10.8 mg/l; GSD: 6.7 mg/l). Lead concentration in whole blood is the biomarker with the best ability to discriminate between individuals with different mean concentration. Urinary and plasma lead also performed acceptably in lead workers, but at low exposures plasma lead was too imprecise. Urinary adjustments appear not to increase the between-individual fraction of the total variance among lead workers but among those with normal lead exposure.
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