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Ljungberg, J., Johansson, B., Engström, K. G., Norberg, M., Bergdahl, I. A. & Söderberg, S. (2019). Arterial hypertension and diastolic blood pressure associate with aortic stenosis. Scandinavian Cardiovascular Journal, 53(2), 91-97
Åpne denne publikasjonen i ny fane eller vindu >>Arterial hypertension and diastolic blood pressure associate with aortic stenosis
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2019 (engelsk)Inngår i: Scandinavian Cardiovascular Journal, ISSN 1401-7431, E-ISSN 1651-2006, Vol. 53, nr 2, s. 91-97Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

OBJECTIVES: Due to age-related differences in aortic valve structure, it is likely that the pathophysiology of aortic stenosis (AS) and associated risk factors differ between age groups. Here we prospectively studied the influence of traditional cardiovascular risk factors on AS development requiring surgery among patients without concomitant coronary artery disease (CAD) and stratified for age.

DESIGN: This study included 322 patients, who had prior to surgery for AS participated in population-based surveys, and 131 of them had no visible CAD upon preoperative coronary angiogram. For each case, we selected four referents matched for age, gender, and geographic area. To identify predictors for surgery, we used multivariable conditional logistic regression with a model including arterial hypertension (or measured blood pressure and antihypertensive medication), cholesterol levels, diabetes, body mass index (BMI), and smoking.

RESULTS: In patients without CAD, future surgery for AS was associated with arterial hypertension and elevated levels of diastolic blood pressure in patients younger than 60 years at surgery (odds ratio [95% confidence interval]), (3.40 [1.45-7.93] and 1.60 [1.09-2.37], respectively), and with only impaired fasting glucose tolerance in patients 60 years or older at surgery (3.22 [1.19-8.76]).

CONCLUSION: Arterial hypertension and elevated diastolic blood pressure are associated with a risk for AS requiring surgery in subjects below 60 years of age. Strict blood pressure control in this group is strongly advocated to avoid other cardiovascular diseases correlated to hypertension. If hypertension and elevated diastolic blood pressure are risk factors for developing AS requiring surgery need further investigations. Notably, elevated fasting glucose levels were related to AS requiring surgery in older adults without concomitant CAD.

sted, utgiver, år, opplag, sider
Taylor & Francis Group, 2019
Emneord
Aortic stenosis, bicuspid aortic valve, diabetes, hypertension, valve disease surgery
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-159471 (URN)10.1080/14017431.2019.1605094 (DOI)000469026200007 ()31109205 (PubMedID)
Forskningsfinansiär
Swedish Heart Lung Foundation, 20140799Swedish Heart Lung Foundation, 20120631Swedish Heart Lung Foundation, 20100635Västerbotten County Council, VLL-548791
Tilgjengelig fra: 2019-05-28 Laget: 2019-05-28 Sist oppdatert: 2019-06-17bibliografisk kontrollert
Donat-Vargas, C., Bergdahl, I. A., Tornevi, A., Wennberg, M., Sommar, J., Koponen, J., . . . Åkesson, A. (2019). Associations between repeated measure of plasma perfluoroalkyl substances and cardiometabolic risk factors. Environment International, 124, 58-65
Åpne denne publikasjonen i ny fane eller vindu >>Associations between repeated measure of plasma perfluoroalkyl substances and cardiometabolic risk factors
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2019 (engelsk)Inngår i: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 124, s. 58-65Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

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.

sted, utgiver, år, opplag, sider
Elsevier, 2019
Emneord
Cardiometabolic risk factors, Environmental epidemiology, Hypertension, Lipids, Plasma perfluoroalkyl substances, Prospective assessment, Repeated measurements
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-156228 (URN)10.1016/j.envint.2019.01.007 (DOI)000457122700007 ()30639908 (PubMedID)2-s2.0-85059696116 (Scopus ID)
Forskningsfinansiär
Forte, Swedish Research Council for Health, Working Life and Welfare, 2012-0758Västerbotten County CouncilSwedish Research Council, 2017-00822
Tilgjengelig fra: 2019-02-08 Laget: 2019-02-08 Sist oppdatert: 2019-02-22bibliografisk kontrollert
Gaudet, M. M., Deubler, E. L., Kelly, R. S., Diver, W. R., Teras, L. R., Hodge, J. M., . . . Kyrtopoulos, S. A. (2019). Blood Levels of Cadmium and Lead in Relation to Breast Cancer Risk in Three Prospective Cohorts.. International Journal of Cancer, 144(5), 1010-1016
Åpne denne publikasjonen i ny fane eller vindu >>Blood Levels of Cadmium and Lead in Relation to Breast Cancer Risk in Three Prospective Cohorts.
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2019 (engelsk)Inngår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 144, nr 5, s. 1010-1016Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

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. 

sted, utgiver, år, opplag, sider
Wiley-Blackwell, 2019
Emneord
breast cancer, cadmium, lead
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-152113 (URN)10.1002/ijc.31805 (DOI)000455041700009 ()30117163 (PubMedID)
Forskningsfinansiär
Swedish Research CouncilVästerbotten County Council
Tilgjengelig fra: 2018-09-27 Laget: 2018-09-27 Sist oppdatert: 2019-01-28bibliografisk kontrollert
Tornevi, A., Sommar, J., Rantakokko, P., Åkesson, A., Donat-Vargas, C., Kiviranta, H., . . . Bergdahl, I. A. (2019). Chlorinated persistent organic pollutants and type 2 diabetes - A population-based study with pre- and post- diagnostic plasma samples. Environmental Research, 174, 35-45
Åpne denne publikasjonen i ny fane eller vindu >>Chlorinated persistent organic pollutants and type 2 diabetes - A population-based study with pre- and post- diagnostic plasma samples
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2019 (engelsk)Inngår i: Environmental Research, ISSN 0013-9351, E-ISSN 1096-0953, Vol. 174, s. 35-45Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

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.

sted, utgiver, år, opplag, sider
Elsevier, 2019
Emneord
Biomonitoring, Longitudinal data, POPs, Polychlorinated biphenyl congeners, Type 2 diabetes
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-158688 (URN)10.1016/j.envres.2019.04.017 (DOI)000470801100005 ()31029940 (PubMedID)
Forskningsfinansiär
Forte, Swedish Research Council for Health, Working Life and Welfare, 2012-0758Swedish Research Council, VR 2017-00650
Tilgjengelig fra: 2019-05-07 Laget: 2019-05-07 Sist oppdatert: 2019-07-10bibliografisk kontrollert
Georgiadis, P., Gavriil, M., Rantakokko, P., Ladoukakis, E., Botsivali, M., Kelly, R. S., . . . Kyrtopoulos, S. A. (2019). DNA methylation profiling implicates exposure to PCBs in the pathogenesis of B-cell chronic lymphocytic leukemia. Environment International, 126, 24-36
Åpne denne publikasjonen i ny fane eller vindu >>DNA methylation profiling implicates exposure to PCBs in the pathogenesis of B-cell chronic lymphocytic leukemia
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2019 (engelsk)Inngår i: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 126, s. 24-36Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

OBJECTIVES: To characterize the impact of PCB exposure on DNA methylation in peripheral blood leucocytes and to evaluate the corresponding changes in relation to possible health effects, with a focus on B-cell lymphoma.

METHODS: We conducted an epigenome-wide association study on 611 adults free of diagnosed disease, living in Italy and Sweden, in whom we also measured plasma concentrations of 6 PCB congeners, DDE and hexachlorobenzene.

RESULTS: We identified 650 CpG sites whose methylation correlates strongly (FDR < 0.01) with plasma concentrations of at least one PCB congener. Stronger effects were observed in males and in Sweden. This epigenetic exposure profile shows extensive and highly statistically significant overlaps with published profiles associated with the risk of future B-cell chronic lymphocytic leukemia (CLL) as well as with clinical CLL (38 and 28 CpG sites, respectively). For all these sites, the methylation changes were in the same direction for increasing exposure and for higher disease risk or clinical disease status, suggesting an etiological link between exposure and CLL. Mediation analysis reinforced the suggestion of a causal link between exposure, changes in DNA methylation and disease. Disease connectivity analysis identified multiple additional diseases associated with differentially methylated genes, including melanoma for which an etiological link with PCB exposure is established, as well as developmental and neurological diseases for which there is corresponding epidemiological evidence. Differentially methylated genes include many homeobox genes, suggesting that PCBs target stem cells. Furthermore, numerous polycomb protein target genes were hypermethylated with increasing exposure, an effect known to constitute an early marker of carcinogenesis.

CONCLUSIONS: This study provides mechanistic evidence in support of a link between exposure to PCBs and the etiology of CLL and underlines the utility of omic profiling in the evaluation of the potential toxicity of environmental chemicals.

Emneord
B-cell lymphoma, DNA methylation, Environmental toxicology, Hazard assessment, Molecular epidemiology, Persistent organic pollutants
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-157883 (URN)10.1016/j.envint.2019.01.068 (DOI)000462597500004 ()30776747 (PubMedID)
Tilgjengelig fra: 2019-04-05 Laget: 2019-04-05 Sist oppdatert: 2019-04-15bibliografisk kontrollert
Löfstedt, A., Ahlm, C., Tesi, B., Bergdahl, I., Nordenskjöld, M., Bryceson, Y. T., . . . Meeths, M. (2019). Haploinsufficiency of UNC13D increases the risk of lymphoma. Cancer, 125(11), 1848-1854
Åpne denne publikasjonen i ny fane eller vindu >>Haploinsufficiency of UNC13D increases the risk of lymphoma
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2019 (engelsk)Inngår i: Cancer, ISSN 0008-543X, E-ISSN 1097-0142, Vol. 125, nr 11, s. 1848-1854Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

BACKGROUND: Experimental models have demonstrated that immune surveillance by cytotoxic lymphocytes can protect from spontaneous neoplasms and cancer. In humans, defective lymphocyte cytotoxicity is associated with the development of hemophagocytic lymphohistiocytosis, a hyperinflammatory syndrome. However, to the best of the authors' knowledge, the degree to which human lymphocyte cytotoxicity protects from cancer remains unclear. In the current study, the authors examined the risk of lymphoma attributable to haploinsufficiency in a gene required for lymphocyte cytotoxicity.

METHODS: The authors exploited a founder effect of an UNC13D inversion, which abolishes Munc13-4 expression and causes hemophagocytic lymphohistiocytosis in an autosomal recessive manner. Within 2 epidemiological screening programs in northern Sweden, an area demonstrating a founder effect of this specific UNC13D mutation, all individuals with a diagnosis of lymphoma (487 patients) and matched controls (1844 controls) were assessed using polymerase chain reaction for carrier status.

RESULTS: Among 487 individuals with lymphoma, 15 (3.1%) were heterozygous carriers of the UNC13D inversion, compared with 18 controls (1.0%) (odds ratio, 3.0; P = .002). It is interesting to note that a higher risk of lymphoma was attributed to female carriers (odds ratio, 3.7; P = .004).

CONCLUSIONS: Establishing a high regional prevalence of the UNC13D inversion, the authors have reported an overrepresentation of this mutation in individuals with lymphoma. Therefore, the results of the current study indicate that haploinsufficiency of a gene required for lymphocyte cytotoxicity can predispose patients to lymphoma, suggesting the importance of cytotoxic lymphocyte-mediated surveillance of cancer. Furthermore, the results of the current study suggest that female carriers are more susceptible to lymphoma.

sted, utgiver, år, opplag, sider
John Wiley & Sons, 2019
Emneord
cancer, hemophagocytic lymphohistiocytosis, immune surveillance, lymphocyte cytotoxicity, lymphoma
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-157884 (URN)10.1002/cncr.32011 (DOI)000467473000015000467473000015 ()30758854 (PubMedID)2-s2.0-85061503911 (Scopus ID)
Tilgjengelig fra: 2019-04-05 Laget: 2019-04-05 Sist oppdatert: 2019-06-13bibliografisk kontrollert
Espín-Pérez, A., Hebels, D. G. A., Kiviranta, H., Rantakokko, P., Georgiadis, P., Botsivali, M., . . . de Kok, T. M. C. (2019). Identification of Sex-Specific Transcriptome Responses to Polychlorinated Biphenyls (PCBs). Scientific Reports, 9, Article ID 746.
Åpne denne publikasjonen i ny fane eller vindu >>Identification of Sex-Specific Transcriptome Responses to Polychlorinated Biphenyls (PCBs)
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2019 (engelsk)Inngår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, artikkel-id 746Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

PCBs are classified as xenoestrogens and carcinogens and their health risks may be sex-specific. To identify potential sex-specific responses to PCB-exposure we established gene expression profiles in a population study subdivided into females and males. Gene expression profiles were determined in a study population consisting of 512 subjects from the EnviroGenomarkers project, 217 subjects who developed lymphoma and 295 controls were selected in later life. We ran linear mixed models in order to find associations between gene expression and exposure to PCBs, while correcting for confounders, in particular distribution of white blood cells (WBC), as well as random effects. The analysis was subdivided according to sex and development of lymphoma in later life. The changes in gene expression as a result of exposure to the six studied PCB congeners were sex- and WBC type specific. The relatively large number of genes that are significantly associated with PCB-exposure in the female subpopulation already indicates different biological response mechanisms to PCBs between the two sexes. The interaction analysis between different PCBs and WBCs provides only a small overlap between sexes. In males, cancer-related pathways and in females immune system-related pathways are identified in association with PCBs and WBCs. Future lymphoma cases and controls for both sexes show different responses to the interaction of PCBs with WBCs, suggesting a role of the immune system in PCB-related cancer development.

sted, utgiver, år, opplag, sider
Nature Publishing Group, 2019
HSV kategori
Forskningsprogram
epidemiologi
Identifikatorer
urn:nbn:se:umu:diva-155826 (URN)10.1038/s41598-018-37449-y (DOI)000456554600185 ()30679748 (PubMedID)
Tilgjengelig fra: 2019-01-28 Laget: 2019-01-28 Sist oppdatert: 2019-02-26bibliografisk kontrollert
Späth, F., Wibom, C., Krop, E. J., Izarra Santamaria, A., Johansson, A. S., Bergdahl, I., . . . Melin, B. S. (2019). Immune marker changes and risk of multiple myeloma: a nested case-control study using repeated prediagnostic blood samples.. Haematologica, Article ID haematol.2019.216895.
Åpne denne publikasjonen i ny fane eller vindu >>Immune marker changes and risk of multiple myeloma: a nested case-control study using repeated prediagnostic blood samples.
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2019 (engelsk)Inngår i: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, artikkel-id haematol.2019.216895Artikkel i tidsskrift (Fagfellevurdert) Epub ahead of print
Abstract [en]

Biomarkers reliably predicting progression to multiple myeloma are lacking. Myeloma risk has been associated with low blood levels of monocyte chemotactic protein 3, macrophage inflammatory protein 1 alpha, vascular endothelial growth factor, fibroblast growth factor 2, fractalkine, and transforming growth factor alpha. In this study, we aimed to replicate these findings and study the individual dynamics of each marker in a prospective longitudinal cohort, thereby examining their potential as markers of myeloma progression. For this purpose, we identified 65 myeloma cases and 65 matched cancer-free controls each with two donated blood samples within the Northern Sweden Health and Disease Study. Samples from myeloma cases were donated in median 13 and 4 years before myeloma diagnosis. Known risk factors of progression were determined by protein-, and immunofixation electrophoresis, and free light chain assays. We observed lower levels of monocyte chemotactic protein 3, vascular endothelial growth factor, fibroblast growth factor 2, fractalkine, and transforming growth factor alpha in myeloma patients than controls, consistent with previous data. We also observed that these markers decreased among future myeloma patients while remaining stable in controls. Decreasing trajectories were marked for transforming growth factor alpha (P = 2.5 x 10-4) indicating progression to multiple myeloma. Investigating this, we found that low levels of transforming growth factor alpha assessed at time of the repeated sample were independently associated with risk of progression in a multivariable model (hazard ratio = 3.5; P = 0.003). Transforming growth factor alpha can potentially improve early detection of multiple myeloma. .

Emneord
Immune marker change, Monoclonal Gammopathy of Undetermined Significance, Multiple Myeloma, Progression, prospective longitudinal study
Identifikatorer
urn:nbn:se:umu:diva-158803 (URN)10.3324/haematol.2019.216895 (DOI)30948485 (PubMedID)
Tilgjengelig fra: 2019-05-09 Laget: 2019-05-09 Sist oppdatert: 2019-05-10
Shi, L., Brunius, C., Bergdahl, I., Johansson, I., Rolandsson, O., Donat Vargas, C., . . . Landberg, R. (2019). Joint Analysis of Metabolite Markers of Fish Intake and Persistent Organic Pollutants in Relation to Type 2 Diabetes Risk in Swedish Adults. Journal of Nutrition, 149(8), 1413-1423
Åpne denne publikasjonen i ny fane eller vindu >>Joint Analysis of Metabolite Markers of Fish Intake and Persistent Organic Pollutants in Relation to Type 2 Diabetes Risk in Swedish Adults
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2019 (engelsk)Inngår i: Journal of Nutrition, ISSN 0022-3166, E-ISSN 1541-6100, Vol. 149, nr 8, s. 1413-1423Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

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.

Emneord
O2PLS modeling, fish biomarkers, metabolomics, nested case-control study, persistent organic pollutants, type 2 diabetes
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-162531 (URN)10.1093/jn/nxz068 (DOI)31209490 (PubMedID)
Tilgjengelig fra: 2019-08-21 Laget: 2019-08-21 Sist oppdatert: 2019-08-23bibliografisk kontrollert
Gasull, M., Pumarega, J., Kiviranta, H., Rantakokko, P., Raaschou-Nielsen, O., Bergdahl, I. A., . . . Porta, M. (2019). Methodological issues in a prospective study on plasma concentrations of persistent organic pollutants and pancreatic cancer risk within the EPIC cohort. Environmental Research, 169, 417-433
Åpne denne publikasjonen i ny fane eller vindu >>Methodological issues in a prospective study on plasma concentrations of persistent organic pollutants and pancreatic cancer risk within the EPIC cohort
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2019 (engelsk)Inngår i: Environmental Research, ISSN 0013-9351, E-ISSN 1096-0953, Vol. 169, s. 417-433Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

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.

sted, utgiver, år, opplag, sider
Elsevier, 2019
Emneord
Biomarkers, methods, Disease progression bias, Environmental epidemiology, Lipids, Pancreatic cancer, Persistent organic pollutants
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-154577 (URN)10.1016/j.envres.2018.11.027 (DOI)000458592200045 ()30529143 (PubMedID)
Tilgjengelig fra: 2018-12-19 Laget: 2018-12-19 Sist oppdatert: 2019-04-15bibliografisk kontrollert
Prosjekter
Könsskillnader i hur stroke och hjärtinfarkt relaterar till fiskkonsumtion, metylkvicksilver, fiskfetter och selen [2007-2024_Formas]; Umeå universitetVarför är diabetes typ 2 så starkt kopplat till koncentrationen av långlivade organiska miljöföroreningar i blodplasma? En fa... [2012-00758_Forte]; Umeå universitet
Organisasjoner
Identifikatorer
ORCID-id: ORCID iD iconorcid.org/0000-0003-1227-6859