| 11. |
- Porta, Miquel, et al.
(författare)
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Plasma concentrations of persistent organic pollutants and pancreatic cancer risk
- 2022
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Ingår i: International Journal of Epidemiology. - : Oxford University Press. - 0300-5771 .- 1464-3685. ; 51:2, s. 479-490
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Tidskriftsartikel (refereegranskat)abstract
- Background: Findings and limitations of previous studies on persistent organic pollutants (POPs) and pancreatic cancer risk support conducting further research in prospective cohorts.Methods: We conducted a prospective case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Participants were 513 pancreatic cancer cases and 1020 matched controls. Concentrations of 22 POPs were measured in plasma collected at baseline.Results: Some associations were observed at higher concentrations of p, p'-DDT, trans-nonachlor, β-hexachlorocyclohexane and the sum of six organochlorine pesticides and of 16 POPs. The odds ratio (OR) for the upper quartile of trans-nonachlor was 1.55 (95% confidence interval 1.06-2.26; P for trend = 0.025). Associations were stronger in the groups predefined as most valid (participants having fasted >6 h, with microscopic diagnostic confirmation, normal weight, and never smokers), and as most relevant (follow-up ≥10 years). Among participants having fasted >6 h, the ORs were relevant for 10 of 11 exposures. Higher ORs were also observed among cases with microscopic confirmation than in cases with a clinical diagnosis, and among normal-weight participants than in the rest of participants. Among participants with a follow-up ≥10 years, estimates were higher than in participants with a shorter follow-up (for trans-nonachlor: OR = 2.14, 1.01 to 4.53, P for trend = 0.035). Overall, trans-nonachlor, three PCBs and the two sums of POPs were the exposures most clearly associated with pancreatic cancer risk.Conclusions: Individually or in combination, most of the 22 POPs analysed did not or only moderately increased the risk of pancreatic cancer.
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| 12. |
- Schillemans, Tessa, et al.
(författare)
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Associations of PFAS-related plasma metabolites with cholesterol and triglyceride concentrations
- 2023
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Ingår i: Environmental Research. - : Elsevier BV. - 0013-9351 .- 1096-0953. ; 216
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Tidskriftsartikel (refereegranskat)abstract
- The wide-spread environmental pollutants per- and polyfluoroalkyl substances (PFAS) have repeatedly been associated with elevated serum cholesterol in humans. However, underlying mechanisms are still unclear. Furthermore, we have previously observed inverse associations with plasma triglycerides. To better understand PFAS-induced effects on lipid pathways we investigated associations of PFAS-related metabolite features with plasma cholesterol and triglyceride concentrations. We used 290 PFAS-related metabolite features that we previously discovered from untargeted liquid chromatography-mass spectometry metabolomics in a case-control study within the Swedish Västerbotten Intervention Programme cohort. Herein, we studied associations of these PFAS-related metabolite features with plasma cholesterol and triglyceride concentrations in plasma samples from 187 healthy control subjects collected on two occasions between 1991 and 2013. The PFAS-related features did not associate with cholesterol, but 50 features were associated with triglycerides. Principal component analysis on these features indicated that one metabolite pattern, dominated by glycerophospholipids, correlated with longer chain PFAS and associated inversely with triglycerides (both cross-sectionally and prospectively), after adjustment for confounders. The observed time-trend of the metabolite pattern resembled that of the longer chain PFAS, with higher levels during the years 2004–2010. Mechanisms linking PFAS exposures to triglycerides may thus occur via longer chain PFAS affecting glycerophospholipid metabolism. If the results reflect a cause-effect association, as implied by the time-trend and prospective analyses, this may affect the general adult population.
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| 13. |
- Schillemans, Tessa, et al.
(författare)
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Omics signatures linking persistent organic pollutants to cardiovascular disease in the Swedish mammography cohort
- 2024
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 58:2, s. 1036-1047
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Tidskriftsartikel (refereegranskat)abstract
- Cardiovascular disease (CVD) development may be linked to persistent organic pollutants (POPs), including organochlorine compounds (OCs) and perfluoroalkyl and polyfluoroalkyl substances (PFAS). To explore underlying mechanisms, we investigated metabolites, proteins, and genes linking POPs with CVD risk. We used data from a nested case-control study on myocardial infarction (MI) and stroke from the Swedish Mammography Cohort - Clinical (n = 657 subjects). OCs, PFAS, and multiomics (9511 liquid chromatography-mass spectrometry (LC-MS) metabolite features; 248 proteins; 8110 gene variants) were measured in baseline plasma. POP-related omics features were selected using random forest followed by Spearman correlation adjusted for confounders. From these, CVD-related omics features were selected using conditional logistic regression. Finally, 29 (for OCs) and 12 (for PFAS) unique features associated with POPs and CVD. One omics subpattern, driven by lipids and inflammatory proteins, associated with MI (OR = 2.03; 95% CI = 1.47; 2.79), OCs, age, and BMI, and correlated negatively with PFAS. Another subpattern, driven by carnitines, associated with stroke (OR = 1.55; 95% CI = 1.16; 2.09), OCs, and age, but not with PFAS. This may imply that OCs and PFAS associate with different omics patterns with opposite effects on CVD risk, but more research is needed to disentangle potential modifications by other factors.
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| 14. |
- Schillemans, Tessa, et al.
(författare)
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Per-and Polyfluoroalkyl Substances and Risk of Myocardial Infarction and Stroke : A Nested Case–Control Study in Sweden
- 2022
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Ingår i: Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 130:3
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Per-and polyfluoroalkyl substances (PFAS) are widespread and persistent pollutants that have been associated with elevated cholesterol levels. However, data on incident cardiovascular disease (CVD) is lacking. OBJECTIVES: We investigated the association of exposure to PFAS with risk of myocardial infarction and stroke and, subsidiary, with baseline blood lipids. METHODS: This population-based nested case–control study included first incident myocardial infarction and stroke cases with matched controls from two Swedish cohorts: the Swedish Mammography Cohort-Clinical (SMC-C) and the Cohort of 60-year-olds (60YO). Baseline blood sampling occurred during 2003–2009 and 1997–1999 with follow-up through 2017 and 2014 for the SMC-C and the 60YO, respectively. Eight plasma PFAS concentrations were measured using targeted liquid chromatography–triple quadrupole mass spectrometry. Five of these were quantifiable in both cohorts; individual values and their standardized sum were categorized into tertiles based on the controls. First incident myocardial infarction (n = 345) and ischemic stroke (n = 354) cases were ascertained via linkage to the National Inpatient Register and the Cause of Death Register. Controls were randomly selected from each cohort after matching for age, sex, and sample date. Baseline blood lipids were measured in plasma or serum after overnight fasting. RESULTS: Among the 1,528 case–control subjects, the mean (standard deviation) age was 66 (7.7) y and 67% of them were women. In multivariable-adjusted analyses, the third tertile of the standardized sum of five PFAS associated with higher cholesterol and lower triglyceride levels among controls at baseline (n = 631). The corresponding results were odds ratios = 0:70 [95% confidence interval (CI): 0.53, 0.93] for CVD, 0.60 (95% CI: 0.39, 0.92) for myocardial infarction, and 0.83 (95% CI: 0.46, 1.50) for stroke. DISCUSSION: This study indicated that exposure to PFAS, although associated with increased cholesterol levels, did not associate with an increased risk of myocardial infarction, stroke, or their composite end point. The findings improve our knowledge on potential health effects of environmental contaminants in the CVD context. https://doi.org/10.1289/EHP9791.
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| 15. |
- Schillemans, Tessa, et al.
(författare)
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Plasma metabolites associated with exposure to perfluoroalkyl substances and risk of type 2 diabetes – A nested case-control study
- 2021
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Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 146
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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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| 16. |
- Shi, Lin, 1988, et al.
(författare)
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Joint Analysis of Metabolite Markers of Fish Intake and Persistent Organic Pollutants in Relation to Type 2 Diabetes Risk in Swedish Adults
- 2019
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Ingår i: Journal of Nutrition. - : Elsevier BV. - 1541-6100 .- 0022-3166. ; 149:8, s. 1413-1423
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND : There is conflicting evidence regarding the association between fish intake and type 2 diabetes (T2D) incidence, possibly owing to measurement errors in self-reported intake and coexposure to persistent organic pollutants (POPs) present in fish. OBJECTIVE : The aim of this study was to identify plasma metabolites associated with fish intake and to assess their association with T2D risk, independently of POPs, in Swedish adults. METHODS : In a case-control study nested in the Swedish Västerbotten Intervention Programme, fasting plasma samples from 421 matched T2D case-control pairs of men and women aged 30-60 y at baseline and 10-y follow-up samples from a subset of 149 pairs were analyzed using untargeted metabolomics. Moreover, 16 plasma POPs were analyzed for the 149 pairs who had repeated samples available. Fish-related plasma metabolites were identified using multivariate modelling and partial correlation analysis. Reproducibility of metabolites and metabolite patterns, derived via principal component analysis (PCA), was assessed by intraclass correlation. A unique component of metabolites unrelated to POPs was dissected by integrating metabolites and POPs using 2-way orthogonal partial least squares regression. ORs of T2D were estimated using conditional logistic regression. RESULTS : We identified 31 metabolites associated with fish intake that had poor to good reproducibility. A PCA-derived metabolite pattern strongly correlated with fish intake (ρ = 0.37, P < 0.001) but showed no association with T2D risk. Integrating fish-related metabolites and POPs led to a unique metabolite component independent of POPs, which tended to be inversely associated with T2D risk (OR: 0.75; 95% CI: 0.54, 1.02, P = 0.07). This component mainly consisted of metabolites reflecting fatty fish intake. CONCLUSIONS: Our results suggest that fatty fish intake may be beneficial for T2D prevention, after removing the counteractive effects of coexposure to POPs in Swedish adults. Integrating metabolite markers and POP exposures appears a promising approach to advance the understanding of associations between fish intake and T2D incidence.
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| 17. |
- Soderlund, Fredri, et al.
(författare)
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The Fate of Phosphate: Assessing Dietary Intake and Urinary Excretion in Swedish Adolescents
- 2024
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Ingår i: CURRENT DEVELOPMENTS IN NUTRITION. - : Elsevier. - 2475-2991. ; 8:7
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Tidskriftsartikel (refereegranskat)abstract
- Background: A high total phosphorus (P) intake has been proposed to promote endothelial dysfunction and atherosclerosis. A diet rich in foods containing P additives could contribute to an excessive intake, potentially reflected as increased concentration of P in urine. Objectives: This study aimed to assess the intake of total dietary P, P additives, and its sources and examine their correlation with urinary P in a cross-sectional national study in Swedish adolescents. Methods: We constructed a database of P additives and applied it to the foods consumed by 3099 participants in the representative schoolbased dietary survey Riksmaten Adolescents 2016 - 17. Intake of total dietary P and P additives were assessed using two 24-h recalls. Urinary P was analyzed in a subsample of 756 participants using inductively coupled plasma mass spectrometry. Spearman rank correlation ( rho ) was used to assess the association between dietary P intake and urinary P excretion. Results: The mean (SD) intake of total P was 1538 ( +/- 667) mg/d. Food containing P additives were consumed by 92% of adolescents and the median (IQR) intake was 49 (22 - 97; range: 0.01 - 947) mg/d, corresponding to 5% (1% - 6%; range: 0% - 50%) of total P. The main contributing food to P additives was cola drinks, while the main contributing food group was sausage dishes. Total P intake was weakly correlated with urinary P ( rho = 0.12; P < 0.01) but not with intake of P additives. Conclusions: Nearly, all participants consumed P additives, contributing to an average of 5% of total P intake but ranging up to 50%. The intake of total P, but not P additives, was weakly reflected in the urinary P. Access to more comprehensive information on P additives in foods would improve further evaluation of potential health consequences.
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| 18. |
- Söderlund, Fredri, et al.
(författare)
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The Fate of Phosphate : Assessing Dietary Intake and Urinary Excretion in Swedish Adolescents
- 2024
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Ingår i: Current Developments in Nutrition. - : Elsevier. - 2475-2991. ; 8:7
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Tidskriftsartikel (refereegranskat)abstract
- Background:A high total phosphorus (P) intake has been proposed to promote endothelial dysfunction and atherosclerosis. A diet rich in foods containing P additives could contribute to an excessive intake, potentially reflected as increased concentration of P in urine.Objectives:This study aimed to assess the intake of total dietary P, P additives, and its sources and examine their correlation with urinary P in a cross-sectional national study in Swedish adolescents.Methods:We constructed a database of P additives and applied it to the foods consumed by 3099 participants in the representative schoolbased dietary survey Riksmaten Adolescents 2016 - 17. Intake of total dietary P and P additives were assessed using two 24-h recalls. Urinary P was analyzed in a subsample of 756 participants using inductively coupled plasma mass spectrometry. Spearman rank correlation ( rho ) was used to assess the association between dietary P intake and urinary P excretion.Results:The mean (SD) intake of total P was 1538 ( +/- 667) mg/d. Food containing P additives were consumed by 92% of adolescents and the median (IQR) intake was 49 (22 - 97; range: 0.01 - 947) mg/d, corresponding to 5% (1% - 6%; range: 0% - 50%) of total P. The main contributing food to P additives was cola drinks, while the main contributing food group was sausage dishes. Total P intake was weakly correlated with urinary P ( rho = 0.12; P < 0.01) but not with intake of P additives.Conclusions:Nearly, all participants consumed P additives, contributing to an average of 5% of total P intake but ranging up to 50%. The intake of total P, but not P additives, was weakly reflected in the urinary P. Access to more comprehensive information on P additives in foods would improve further evaluation of potential health consequences.
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| 19. |
- Tagt, Jonas, et al.
(författare)
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Long-term cadmium exposure and fractures, cardiovascular disease, and mortality in a prospective cohort of women
- 2022
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Ingår i: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 161
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cadmium (Cd) is a toxic metal, which the non-smoking population is mainly exposed to through diet. Current health-based guidance values are based on renal toxicity; however, emerging evidence suggests that bone and the cardiovascular system might be more sensitive to Cd exposure. Objective: To assess the association of urinary Cd (U-Cd) with incidence of fractures, myocardial infarction, heart failure, ischemic stroke and mortality in postmenopausal women. Methods: We used data from 4024 women, aged 56-85 in the population-based prospective Swedish Mammography Cohort-Clinical. U-Cd was measured by ICP-MS at baseline (2004-2009) and categorized into tertiles. Incident cases of the outcomes were ascertained via register linkage through 2019. Multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox regression. Results: The median U-Cd at baseline was 0.33 mu g/g creatinine (cr) (5-95 percentiles 0.15-0.77). We ascertained the following incident cases: 903 first fracture of any type, 149 myocardial infarction, 174 heart failure, 162 ischemic stroke and 545 total deaths during the approximately 11 years of follow-up. U-Cd was dose-dependently associated with risk of any fracture (HR: 1.20, 95% CI: 1.01 to 1.43, ptrend: 0.04) and all-cause mortality (HR: 1.38, 95% CI: 1.10 to 1.74, ptrend: <0.01) when comparing the highest tertile of U-Cd (median 0.54 mu g/g cr) with the lowest (median 0.20 mu g/g cr). No clear associations were observed for myocardial infarction, heart failure or stroke. Discussion: Long-term Cd exposure might be associated with risk of fractures and all-cause mortality at lower levels than previously suggested.
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| 20. |
- Tornevi, Andreas, et al.
(författare)
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Chlorinated persistent organic pollutants and type 2 diabetes - A population-based study with pre- and post- diagnostic plasma samples
- 2019
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Ingår i: Environmental Research. - : Elsevier. - 0013-9351 .- 1096-0953. ; 174, s. 35-45
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Persistent organic pollutants (POPs) have been associated with type 2 diabetes (T2D), but causality is uncertain.OBJECTIVE: Within longitudinal population-based data from northern Sweden, we assessed how POPs associated with T2D prospectively and cross-sectionally, and further investigated factors related to individual changes in POP concentrations.METHODS: For 129 case-controls pairs matched by age, sex and date of sampling, plasma concentrations of hexachlorobenzene (HCB), dichlorodiphenyl-dichloroethylene (p,p'-DDE), dioxin-like (DL) polychlorinated biphenyl congeners (PCB-118 and PCB-156), and non-dioxin like (NDL-PCB: PCB-74, -99, -138 -153, -170, -180, -183 and PCB-187) were analyzed twice (baseline and follow-up, 9-20 years apart). The cases received their T2D diagnose between baseline and follow-up. Prospective (using baseline data) and cross-sectional (using follow-up data) odds ratios (ORs) for T2D on lipid standardized POPs (HCB, p,p'-DDE, ∑DL-PCBs, ∑NDL-PCBs) were estimated using conditional logistic regression, adjusting for body mass index (BMI) and plasma lipids. The influence of BMI, weight-change, and plasma lipids on longitudinal changes in POP concentrations were evaluated among non-diabetic individuals (n = 306).RESULTS: POPs were associated with T2D in both the prospective and cross-sectional assessments. Of a standard deviation increase in POPs, prospective ORs ranged 1.42 (95% CI: 0.99, 2.06) for ∑NDL-PCBs to 1.55 (95% CI: 1.01, 2.38) for HCB (p < 0.05 only for HCB), and cross-sectional ORs ranged 1.62 (95% CI: 1.13; 2.32) for p,p'-DDE to 2.06 (95% CI: 1.29, 3.28) for ∑DL-PCBs (p < 0.05 for all POPs). In analyses of non-diabetic individuals, higher baseline BMI, decreased weight and decreased plasma lipid concentrations were associated with a slower decrease of POPs. Cases had, besides a higher BMI, reduced cholesterol and weight gain at follow-up compared to controls, which can explain the higher ORs in the cross-sectional assessments.DISCUSSION: The association between POPs and T2D was confirmed, but an indication that individuals body fat history might influence POP-T2D associations weakens the epidemiological support for a causal association. It also warrants studies based on other exposure metrics than biomonitoring. In addition, we note that a cross-sectional design overestimates the ORs if T2D cases have successfully intervened on weight and/or blood lipids, as changes in these factors cause changes in POPs.
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