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1.
  • Andersson, Eva M., 1968, et al. (författare)
  • Is Cadmium a Risk Factor for Breast Cancer - Results from a Nested Case-Control Study Using Data from the Malmo Diet and Cancer Study
  • 2021
  • Ingår i: Cancer Epidemiology Biomarkers & Prevention. - 1055-9965. ; 30:9, s. 1744-1752
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Some studies have shown that cadmium (Cd) is associated with breast cancer risk. One hypothesis is that Cd has estrogen-like properties. This case-control study investigated the association between breast cancer risk and blood Cd (BCd) levels. Methods: All breast cancers in the Malmo Diet and Cancer cohort were identified through linkage to the Swedish Cancer Registry, baseline (1991-1996) through 2014. Two controls per case were selected from the same cohort. BCd was analyzed at baseline. Associations were analyzed using logistic regression. Results: Mean BCd was 0.51 mg/L among 1,274 cases and 0.46 among 2,572 controls. There was an overall increased risk of breast cancer [OR, 1.18; 95% confidence interval (CI), 1.05-1.36] per mg/L of BCd. An increased risk was, however, only found at high BCd [OR, 1.34 (95% CI, 1.05-1.73)] for BCd more than 1.20 mg/L. The group with the highest BCd was mainly smokers. A spline indicated that at BCd less than 1.0 mg/L, the OR was not increased. The association with BCd was stronger in current smokers and at body mass index (BMI) above 25, while no modification due to receptor status was found. Conclusions: The results indicated increased risk of breast cancer only for high Cd exposure, which occurred mainly among smokers. This made it difficult to disentangle the effects of smoking and Cd, despite inclusion of smoking habits in the models. Impact: This study provides support for reducing Cd exposure through smoking cessation and dietary choice. On the population level, preventive measures against Cd pollution are warranted.
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2.
  • Azzouz, Mehjar, 1999, et al. (författare)
  • Air pollution and biomarkers of cardiovascular disease and inflammation in the Malmo Diet and Cancer cohort
  • 2022
  • Ingår i: Environmental Health. - : Springer Science and Business Media LLC. - 1476-069X. ; 21:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction Air pollution is associated with increased risk of cardiovascular disease, possibly through chronic systemic inflammation that promotes the progression of atherosclerosis and the risk of cardiovascular events. This study aimed to investigate the associations between air pollution and established biomarkers of inflammation and cardiovascular disease. Methods The Cardiovascular Subcohort of the Malmo Diet and Cancer cohort includes 6103 participants from the general population of Malmo, Sweden. The participants were recruited 1991-1994. Annual mean residential exposure to particulate matter < 2.5 and < 10 mu m (PM2.5 and PM10), and nitrogen oxides (NOx) at year of recruitment were assigned from dispersion models. Blood samples collected at recruitment, including blood cell counts, and biomarkers (lymphocyte- and neutrophil counts, C-reactive protein (CRP), soluble urokinase-type plasminogen activator receptor (suPAR), lipoprotein-associated phospholipase A(2) (Lp-PLA(2)), ceruloplasmin, orosomucoid, haptoglobin, complement-C3, and alpha-1-antitrypsin) were analyzed. Multiple linear regression models were used to investigate the cross-sectional associations between air pollutants and biomarkers. Results The mean annual exposure levels in the cohort were only slightly or moderately above the new WHO guidelines of 5 mu g/m(3) PM2.5 (10.5 mu g/m(3) PM2.5). Residential PM2.5 exposure was associated with increased levels of ceruloplasmin, orosomucoid, C3, alpha-1-antitrypsin, haptoglobin, Lp-PLA(2) and the neutrophil-lymphocyte ratio. Ceruloplasmin, orosomucoid, C3 and alpha-1-antitrypsin were also positively associated with PM10. There were no associations between air pollutants and suPAR, leukocyte counts or CRP. The associations between particles and biomarkers were still significant after removing outliers and adjustment for CRP levels. The associations were more prominent in smokers. Conclusion Long-term residential exposure to moderate levels of particulate air pollution was associated with several biomarkers of inflammation and cardiovascular disease. This supports inflammation as a mechanism behind the association between air pollution and cardiovascular disease.
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3.
  • Azzouz, Mehjar, 1999, et al. (författare)
  • Long-term ambient air pollution and venous thromboembolism in a population-based Swedish cohort.
  • 2023
  • Ingår i: Environmental pollution (Barking, Essex : 1987). - : Elsevier. - 1873-6424 .- 0269-7491. ; 331:Pt 1
  • Tidskriftsartikel (refereegranskat)abstract
    • Air pollution is a major contributor to the global burden of disease and has been linked to several diseases and conditions, including cardiovascular disease. The biological mechanisms are related to inflammation and increased coagulability, factors that play an important role in the pathogenesis of venous thromboembolism (VTE, i.e., deep vein thrombosis or pulmonary embolism). This study investigates if long-term exposure to air pollution is associated with increased VTE incidence. The study followed 29408 participants from the Malmö Diet and Cancer (MDC) cohort, which consists of adults aged 44-74 recruited in Malmö, Sweden between 1991 and 1996. For each participant, annual mean residential exposures to particulate matter <2.5μg (PM2.5) and <10μg (PM10), nitrogen oxides (NOx) and black carbon (BC) from 1990 up to 2016 were calculated. Associations with VTE were analysed using Cox proportional hazard models for air pollution in the year of the VTE event (lag0) and the mean of the prior 1-10 years (lag1-10). Annual air pollution exposures for the full follow-up period had the following means: 10.8μg/m3 for PM2.5, 15.8μg/m3 for PM10, 27.7μg/m3 for NOx, and 0.96μg/m3 for BC. The mean follow-up period was 19.5 years, with 1418 incident VTE events recorded during this period. Exposure to lag1-10 PM2.5 was associated with an increased risk of VTE (HR 1.17 (95%CI 1.01-1.37)) per interquartile range (IQR) of 1.2μg/m3 increase in PM2.5 exposure. No significant associations were found between other pollutants or lag0 PM2.5 and incident VTE. When VTE was divided into specific diagnoses, associations with lag1-10 PM2.5 exposure were similarly positive for deep vein thrombosis but not for pulmonary embolism. Results persisted in sensitivity analyses and in multi-pollutant models. Long-term exposure to moderate concentrations of ambient PM2.5 was associated with increased risks of VTE in the general population in Sweden.
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4.
  • Barregård, Lars, 1948, et al. (författare)
  • Cadmium Exposure and Coronary Artery Atherosclerosis: A Cross-Sectional Population-Based Study of Swedish Middle-Aged Adults
  • 2021
  • Ingår i: Environmental health perspectives. - 1552-9924 .- 0091-6765. ; 129:6
  • Tidskriftsartikel (refereegranskat)abstract
    • The general population is ubiquitously exposed to the toxic metal cadmium through the diet and smoking. Cadmium exposure is associated with increased morbidity and mortality in myocardial infarction and stroke. Atherosclerosis is the main underlying mechanism of myocardial infarction. However, associations between cadmium and coronary artery atherosclerosis have not been examined.Our study sought to examine the hypothesis that blood cadmium (B-Cd) is positively associated with coronary artery calcification, as a measure of coronary artery atherosclerosis in the population-based Swedish SCAPIS study.Our analysis included 5,627 individuals (51% women), age 50-64 y, enrolled from 2013 to 2018. The coronary artery calcium score (CACS) was obtained from computed tomography. Blood cadmium was determined by inductively coupled plasma mass spectrometry (ICP-MS). Associations between B-Cd and coronary artery calcium score (CACS Agatston score) were evaluated using prevalence ratios (PRs) in models adjusted for sex, age, smoking, hypertension, diabetes, low-density cholesterol/high-density cholesterol ratio, and family history.The median B-Cd concentration was 0.24 μ g / L . The prevalence of positive coronary artery calcium ( CACS > 0 ) was 41% and the prevalence of CACS ≥ 100 was 13%. Relative to the lowest quartile (Q) of B-Cd ( < 0.16 μ g / L ), the highest quartile (median 0.63 μ g / L ) was associated with a small but significant increase in CACS > 0 (PR 1.1; 95% CI: 1.0, 1.3), and a greater relative increase in CACS ≥ 100 (PR 1.6; 95% CI: 1.3, 2.0). When restricted to 2,446 never-smokers, corresponding PRs were 1.1 (95% CI 0.9, 1.3) for CACS > 0 (63 cases in Q4) and 1.7 (95% CI 1.1, 2.7) for CACS ≥ 100 (17 cases in Q4).Blood cadmium in the highest quartile was associated with CACS in a general population sample with low to moderate cadmium exposure. This supports the hypothesis that atherosclerosis is an important mechanism underlying the associations between cadmium and incident cardiovascular disease. The findings suggest that public health measures to reduce cadmium exposure are warranted. https://doi.org/10.1289/EHP8523.
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5.
  • Barregård, Lars, 1948, et al. (författare)
  • Low-level exposure to lead, cadmium and mercury, and histopathological findings in kidney biopsies
  • 2022
  • Ingår i: Environmental Research. - : Elsevier BV. - 0013-9351. ; 211
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Lead (Pb), cadmium (Cd) and mercury (Hg) are all nephrotoxic metals, and a large part of the body burden of Cd and Hg is found in the kidneys. There are, however, few studies on associations between exposure to these toxic metals and renal biopsy findings, and none at low-level exposure. Aim: To examine the hypothesis that low-level concentration of Pb, Cd or Hg in the kidneys is associated with histopathological changes in the kidneys.& nbsp;Methods: We determined concentrations of Pb, Cd and Hg in kidney, blood and urine in 109 healthy kidney donors, aged 24-70 years. The renal biopsies were scored according to the Banff classification regarding tubular atrophy, interstitial fibrosis, glomerulosclerosis, arteriosclerosis, and arteriolohyalinosis. Kidney function was assessed based on glomerular filtration rate (GFR) as well as urinary excretion of albumin, low molecular weight proteins, kidney injury molecule 1 and N-acetylglucose aminidase. Associations between metal concentrations and histopathological changes, were assessed in models also including age, sex and smoking.& nbsp;Results: The median kidney concentrations of Pb, Cd and Hg were 0.08, 13 and 0.21 mu g/g, respectively. There were signs of tubular atrophy in 63%, interstitial fibrosis in 21%, glomerulosclerosis in 71%, arteriosclerosis in 47%, and arteriolohyalinosis in 36% of the donors, but, as could be expected, the histopathological findings were limited, mostly Banff grade 1. In models adjusted for age, sex and smoking, kidney Cd was positively associated with tubular atrophy (p = 0.03) and possibly with arteriolohyalinosis (p = 0.06). Kidney Hg was associated with arteriosclerosis (p = 0.004).& nbsp;Discussion and conclusions: The results suggest that even low levels of Cd in the kidney can induce a mild degree of tubular atrophy. This is in line with previous findings at high-level Cd exposure. The association between kidney Hg and renal arteriosclerosis was unexpected, and may be a chance finding.
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6.
  • Barregård, Lars, 1948, et al. (författare)
  • Normal variability of 22 elements in 24-hour urine samples - Results from a biobank from healthy non-smoking adults.
  • 2021
  • Ingår i: International journal of hygiene and environmental health. - : Elsevier BV. - 1618-131X .- 1438-4639. ; 233
  • Tidskriftsartikel (refereegranskat)abstract
    • Urine is often used for biomonitoring the exposure to elements. However, most studies report concentrations in spot urine samples, which may not accurately mirror the "gold standard" of complete 24-h (24h) urine samples. There are relatively few data published for 24h samples, and little information on the within- and between person variability.The present study aimed at assessing variability within and between individuals in 24h excretion for a number of elements in adults from the general population and the typical 24h excretion of these elements. In addition, we assessed concentrations adjusted for creatinine and specific gravity (SG), and associations between elements.60 healthy non-smokers (31 women and 29 men) from Sweden, aged 21-64 years, collected all urine during 24h (split into six separate samples) on two occasions, about one week apart. Concentrations of As, Br, Cd, Co, Cr, Cu, Fe, Hg, Li, Mn, Mo, Ni, P, Pb, S, Sb, Se, Sn, U, V, W, and Zn in urine were analyzed by inductively coupled plasma sector-field mass spectrometry (ICP-SF-MS) and 24h excretion rates were calculated for each day. The ratio of between-individual variance and the total variance, the intra-class correlation (ICC) was calculated based on natural log-transformed 24h excretion. Correlation coefficients were calculated between excretion rates (mass/24h), and concentrations adjusted for creatinine and SG.Geometric means (GM), and 90-percentiles are presented for each element. The 24h excretion was higher in men than in women for most elements, and the difference was statistically significant for Cr, Cu, Fe, Li, P, Pb, S, Se, U, V, and Zn. However, for Cd and Co, the excretion was higher in women. Variability between days was low for Cd, Co, Hg, Pb, Sn, Se, V, and Zn (ICC 0.75-0.90), highest for Cr (ICC=0.3) and Sb (ICC=0.18), and moderate for the other elements. Spearman's rank correlation coefficients were about 0.8-0.9 for 17 elements, and 0.3-0.7 for Br, Cu, P, S, Se. Excretion of P and S were highly correlated, and also associated with excretion of most of the other elements, especially Cu, Se, V, and Zn. A high correlation was also found between As and Hg, between Mo and W, as well as between Cr, Fe and Mn.These data present normal variability of 24h excretion of a number of elements, and can also be used as updated reference levels for elements with no or limited previous literature available. Information on variability within- and between individuals is important to know when designing studies with urine levels of elements used as exposure biomarker in studies of associations with health outcomes.
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7.
  • Elinder, C. G., et al. (författare)
  • Renal effects of exposure to metals
  • 2022
  • Ingår i: Handbook on the Toxicology of Metals (Fifth Edition). - 9780128232927 ; , s. 485-506
  • Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
    • Several metals have nephrotoxic properties. In this chapter we discuss various methods for assessing nephrotoxicity, different forms of proteinuria, and methods of estimating the glomerular filtration rate. Metals may affect renal glomeruli, resulting in a decreased glomerular filtration rate, sometimes associated with massive albuminuria. Effects on renal tubular function are more common, affecting the reabsorption of minerals, glucose, amino acids, and low molecular weight proteins from filtered primary urine. Various biomarkers, especially proteinuria, are also discussed. The most important nephrotoxic metals are lead, cadmium, and mercury. Acute nephrotoxic effects are sometimes seen, especially in suicide attempts or as side effects when metals (e.g., gold, platinum, lithium and antimony) are used in treatment of certain diseases. Long-term exposure is more common, e.g., via diet, drinking water, or occupational exposure. For example, long-term exposure to cadmium sometimes causes chronic kidney disease, and in rare cases the development of end-stage renal disease with uremia. Lithium used for treatment of mano-depressive disorders often cause polyuria and sometimes chronic kidney disease. © 2022 Elsevier B.V. All rights reserved.
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8.
  • Ellingsen, D. G., et al. (författare)
  • The variability of arsenic in blood and urine of humans
  • 2023
  • Ingår i: Journal of Trace Elements in Medicine and Biology. - 0946-672X. ; 78
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Humans are exposed to inorganic and organic arsenic. The total arsenic (As) concentration in urine is a commonly used biomarker of exposure. However, little is known about variability of As in biological fluids and the diurnal variation of As excretion.Objectives: Main objectives were to assess the variability of As in urine, plasma (P-As), whole blood (B-As), and the blood cell fraction (C-As), and to assess diurnal variation of As excretion. Methods: Six urine samples were collected at fixed times during 24 h on two different days around one week apart among 29 men and 31 women. Blood samples were collected when the morning urine samples were delivered. The intra-class correlation coefficient (ICC) was calculated as the ratio of the between-individuals variance to the total observed variance.Results: Geometric mean (GM) 24 h urinary excretions of As (U-As24 h) were 41 and 39 mu g/24 h on the two days of sampling. Concentrations of B-As, P-As and C-As were highly correlated with U-As24 h and As in first void morning urine. No statistically significant differences were observed for the urinary As excretion rate between the different sampling times. A high ICC was observed for As in the cellular blood fraction (0.803), while ICC for first morning urine corrected for creatine was low (0.316).Conclusions: The study suggests that C-As is the most reliable biomarker for use in exposure assessment of individual exposure. Morning urine samples have low reliability for such use. No apparent diurnal variation was observed in the urinary As excretion rate.
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9.
  • Eriksson, Janna, 1992, et al. (författare)
  • Urinary iodine excretion and optimal time point for sampling when estimating 24-h urinary iodine
  • 2023
  • Ingår i: British Journal of Nutrition. - : Cambridge University Press (CUP). - 0007-1145 .- 1475-2662. ; 130:8, s. 1289-97
  • Tidskriftsartikel (refereegranskat)abstract
    • Iodine deficiency may cause thyroid dysfunction. The iodine intake in a population is measured by urinary iodine concentration (UIC) in spot samples or 24-h urinary iodine excretion (24UIE). 24UIE is considered the gold standard and may be estimated using an equation including UIC, urinary creatinine concentration, sex and age (e24UIE). The aims of this study were to evaluate the preferable timing of UIC when using this equation and assess the variability of UIE. Sixty healthy non-smoking women (n 31) and men (n 29) were included in Gothenburg, Sweden. Twelve urine samples were collected at six fixed times on two separate days. Variability was calculated for UIC, 24UIE, e24UIE, iodine excretion per hour (iHr) and UIC adjusted for creatinine and specific gravity. Median 24UIE was 156 mu g/24 h and the median UIC (all spot samples) was 104 mu g/l. UIC (P < 0 center dot 001), 24UIE (P = 0 center dot 001) and e24UIE (P < 0 center dot 001) were significantly higher in men. e24UIE was relatively similar to 24UIE. However, when e24UIE was calculated from UIC in the first void, it was about 15 % lower than 24UIE (P < 0 center dot 001). iHr was lowest in the morning and highest in the afternoon. Median iHr was higher in men (7 center dot 4 v. 5 center dot 3 mu g/h, P < 0 center dot 001). The variability of UIE was higher within individuals than between individuals. This study suggests that most time points for estimation of individual 24UIE are appropriate, but they should preferably not be collected in the first void.
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10.
  • Fagerberg, Björn, 1943, et al. (författare)
  • Review of cadmium exposure and smoking-independent effects on atherosclerotic cardiovascular disease in the general population
  • 2021
  • Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 290:6, s. 1153-1179
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Exposure to cadmium (Cd) via food and smoking is associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD). Blood and urine levels of Cd are established biomarkers of exposure. Objectives To review: (1) the smoking-independent associations between Cd exposure and ASCVD, including the possible presence of a nonlinear dose-response relationship with Cd exposure and (2) the causal effects of Cd exposure on different stages of atherosclerosis. Methods Narrative review. Results Cd confers increased risk of ASCVD and asymptomatic atherosclerosis in the carotid and coronary arteries above B-Cd >0.5 mu g/L or U-Cd >0.5 mu g/g creatinine, but it has not been shown below a threshold of these exposure levels. Adjustment for smoking does not exclude the possibility of residual confounding, but several studies in never-smoking cohorts have shown associations between Cd and ASCVD, and experimental studies have demonstrated pro-atherosclerotic effects of Cd. Cd accumulates in arterial walls and atherosclerotic plaques, reaching levels shown to have proatherosclerotic effects. Suggested early effects are increased subendothelial retention of atherogenic lipoproteins, which become oxidized; endothelial dysfunction and damage with increased permeability for monocytes, which in the intima turn to macrophages and then to foam cells. Later, Cd may contribute to plaque rupture and erosion by endothelial apoptosis and degradation of the fibrous cap. Finally, by having prothrombotic and antifibrinolytic effects, the CVD risk may be further increased. Conclusions There is strong evidence that Cd causes ASCVD above a suggested exposure level via mechanisms in early, as well as the late stages of atherosclerotic disease.
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