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Sundkvist, Anneli
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Publications (10 of 17) Show all publications
Myte, R., Sundkvist, A., van Guelpen, B. & Harlid, S. (2019). Circulating levels of inflammatory markers and DNA methylation, an analysis of repeated samples from a population based cohort. Epigenetics, 14(7), 649-659
Open this publication in new window or tab >>Circulating levels of inflammatory markers and DNA methylation, an analysis of repeated samples from a population based cohort
2019 (English)In: Epigenetics, ISSN 1559-2294, E-ISSN 1559-2308, Vol. 14, no 7, p. 649-659Article in journal (Refereed) Published
Abstract [en]

DNA methylation in blood may adapt to conditions affecting our health, such as inflammation, and multiple studies have identified differential DNA methylation related to smoking, obesity and various diseases. The purpose of this study was to evaluate previously reported, and explore possible new, associations between levels of inflammatory markers and DNA methylation in blood. We used a well-characterized study population consisting of 127 individuals, all of whom were participants in the population-based Vasterbotten Intervention Programme cohort and had provided two blood samples, ten years apart. Levels of CRP and 160 other proteins were measured in plasma, and DNA methylation levels (assessed using the 850K Illumina Infinium MethylationEPIC BeadChip) were measured in white blood cell DNA. Associations between CpG methylation and protein levels were estimated using linear mixed models. In the study we were able to confirm the direction for 85 of 102 previously reported protein-methylation associations. Depicting associations in a network allowed us to identify CpG sites with associations to multiple proteins, and ten CpG sites were each associated with three or more inflammatory markers. Furthermore, two genetic regions included nine additional unreported CpG sites that may represent trans-acting methylation sites. Our study supports a complex interaction between DNA methylation and circulating proteins involved in the inflammatory response. The notion of trans-acting methylation sites affecting, or being affected by, the expression of genes on completely different chromosomes should be taken into account when interpreting results from epigenome-wide association studies.

Place, publisher, year, edition, pages
Taylor & Francis, 2019
Keywords
DNA methylation, inflammation, biomarkers, C, reactive protein, colorectal cancer, risk factors, epigenetics, proteomics
National Category
Medical Genetics Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:umu:diva-160622 (URN)10.1080/15592294.2019.1603962 (DOI)000470485500001 ()31033411 (PubMedID)
Funder
Västerbotten County Council, VLL-547711Västerbotten County Council, VLL-680921Västerbotten County Council
Available from: 2019-06-20 Created: 2019-06-20 Last updated: 2019-06-20Bibliographically approved
Lakso, H.-Å., Wuolikainen, A., Sundkvist, A., Johansson, I. & Marklund, S. L. (2019). Long-term stability of the alcohol consumption biomarker phosphatidylethanol in erythrocytes at-80 degrees C. Clinical Mass Spectrometry, 11, 37-41
Open this publication in new window or tab >>Long-term stability of the alcohol consumption biomarker phosphatidylethanol in erythrocytes at-80 degrees C
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2019 (English)In: Clinical Mass Spectrometry, ISSN 2376-9998, Vol. 11, p. 37-41Article in journal (Refereed) Published
Abstract [en]

Phosphatidylethanol (PEth) is a recently introduced biomarker with high specificity, high sensitivity, and response correlating with alcohol consumption. It has the potential to be a valuable biomarker in population studies on the health effects of alcohol, however its stability in long-term stored blood is not known. We used LCMS/MS to assess the stability of PEth-16:0/18:1 in blood samples (packed erythrocytes) that were stored between 1 and 19 years at -80 degrees C in a biobank from a large population survey. The participants answered a lifestyle questionnaire that included questions on alcohol consumption. For analysis, we selected blood samples from seven homogenous ethanol consumption cohorts collected at intervals from 1997 to 2015. Despite the narrow stated alcohol consumption range, 10-15 g/day, there were large differences in PEth values between individuals in the cohorts, from below the limit of detection of 0.005 mu mol/L to 1.40 mu mol/L. The median was 0.08 mu mol/L. Neither generalized linear modeling, nor principal component analysis revealed a statistically significant association between time of storage and PEth levels. The PEth results indicate that the participants had, on average, under-reported their alcohol consumption several-fold. The findings suggest that PEth in blood has a sufficient long-term stability for use as an alcohol biomarker in prospective case-control studies. Analysis of blood stored in biobanks could significantly improve the validity of assessments exploring the health effects of alcohol.

Place, publisher, year, edition, pages
Elsevier, 2019
Keywords
Biobank, Stability, Ethanol, Health effects, Population studies
National Category
Substance Abuse
Identifiers
urn:nbn:se:umu:diva-165732 (URN)10.1016/j.clinms.2018.12.002 (DOI)000496420500006 ()
Funder
Swedish Research CouncilVästerbotten County Council
Available from: 2019-12-10 Created: 2019-12-10 Last updated: 2019-12-10Bibliographically approved
Sundkvist, A., Myte, R., Palmqvist, R., Harlid, S. & van Guelpen, B. (2019). Plasma ghrelin is probably not a useful biomarker for risk prediction or early detection of colorectal cancer [Letter to the editor]. Gut, 68(2), 373-374
Open this publication in new window or tab >>Plasma ghrelin is probably not a useful biomarker for risk prediction or early detection of colorectal cancer
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2019 (English)In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 68, no 2, p. 373-374Article in journal, Letter (Refereed) Published
Place, publisher, year, edition, pages
BMJ Publishing Group Ltd, 2019
Keywords
cancer, colorectal cancer, epidemiology, gastrointestinal hormones
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:umu:diva-146376 (URN)10.1136/gutjnl-2018-316110 (DOI)000459027800022 ()29491131 (PubMedID)
Available from: 2018-04-06 Created: 2018-04-06 Last updated: 2019-04-16Bibliographically approved
Assi, N., Thomas, D. C., Leitzmann, M., Stepien, M., Chajès, V., Philip, T., . . . Viallon, V. (2018). Are Metabolic Signatures Mediating the Relationship between Lifestyle Factors and Hepatocellular Carcinoma Risk? Results from a Nested Case–Control Study in EPIC. Cancer Epidemiology, Biomarkers and Prevention, 27(5), 531-540
Open this publication in new window or tab >>Are Metabolic Signatures Mediating the Relationship between Lifestyle Factors and Hepatocellular Carcinoma Risk? Results from a Nested Case–Control Study in EPIC
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2018 (English)In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 27, no 5, p. 531-540Article in journal (Refereed) Published
Abstract [en]

Background: The "meeting-in-the-middle" (MITM) is a principle to identify exposure biomarkers that are also predictors of disease. The MITM statistical framework was applied in a nested case-control study of hepatocellular carcinoma (HCC) within European Prospective Investigation into Cancer and Nutrition (EPIC), where healthy lifestyle index (HLI) variables were related to targeted serum metabolites.

Methods: Lifestyle and targeted metabolomic data were available from 147 incident HCC cases and 147 matched controls. Partial least squares analysis related 7 lifestyle variables from a modified HLI to a set of 132 serum-measured metabolites and a liver function score. Mediation analysis evaluated whether metabolic profiles mediated the relationship between each lifestyle exposure and HCC risk.

Results: Exposure-related metabolic signatures were identified. Particularly, the body mass index (BMI)-associated metabolic component was positively related to glutamic acid, tyrosine, PC aaC38:3, and liver function score and negatively to lysoPC aC17:0 and aC18:2. The lifetime alcohol-specific signature had negative loadings on sphingomyelins (SM C16:1, C18:1, SM(OH) C14:1, C16:1 and C22:2). Both exposures were associated with increased HCC with total effects (TE) = 1.23 (95% confidence interval = 0.93-1.62) and 1.40 (1.14-1.72), respectively, for BMI and alcohol consumption. Both metabolic signatures mediated the association between BMI and lifetime alcohol consumption and HCC with natural indirect effects, respectively, equal to 1.56 (1.24-1.96) and 1.09 (1.03-1.15), accounting for a proportion mediated of 100% and 24%.

Conclusions: In a refined MITM framework, relevant metabolic signatures were identified as mediators in the relationship between lifestyle exposures and HCC risk.

Impact: The understanding of the biological basis for the relationship between modifiable exposures and cancer would pave avenues for clinical and public health interventions on metabolic mediators.

National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:umu:diva-150026 (URN)10.1158/1055-9965.EPI-17-0649 (DOI)29563134 (PubMedID)
Available from: 2018-07-03 Created: 2018-07-03 Last updated: 2018-08-10Bibliographically approved
Assi, N., Gunter, M. J., Thomas, D. C., Leitzmann, M., Stepien, M., Chajès, V., . . . Ferrari, P. (2018). Metabolic signature of healthy lifestyle and its relation with risk of hepatocellular carcinoma in a large European cohort. American Journal of Clinical Nutrition, 108(1), 117-126
Open this publication in new window or tab >>Metabolic signature of healthy lifestyle and its relation with risk of hepatocellular carcinoma in a large European cohort
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2018 (English)In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 108, no 1, p. 117-126Article in journal (Refereed) Published
Abstract [en]

Background: Studies using metabolomic data have identified metabolites from several compound classes that are associated with disease-related lifestyle factors.

Objective: In this study, we identified metabolic signatures reflecting lifestyle patterns and related them to the risk of hepatocellular carcinoma (HCC) in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

Design: Within a nested case-control study of 147 incident HCC cases and 147 matched controls, partial least squares (PLS) analysis related 7 modified healthy lifestyle index (HLI) variables (diet, BMI, physical activity, lifetime alcohol, smoking, diabetes, and hepatitis) to 132 targeted serum-measured metabolites and a liver function score. The association between the resulting PLS scores and HCC risk was examined in multivariable conditional logistic regression models, where ORs and 95% CIs were computed.

Results: The lifestyle component's PLS score was negatively associated with lifetime alcohol, BMI, smoking, and diabetes, and positively associated with physical activity. Its metabolic counterpart was positively related to the metabolites sphingomyelin (SM) (OH) C14:1, C16:1, and C22:2, and negatively related to glutamate, hexoses, and the diacyl-phosphatidylcholine PC aaC32:1. The lifestyle and metabolomics components were inversely associated with HCC risk, with the ORs for a 1-SD increase in scores equal to 0.53 (95% CI: 0.38, 0.74) and 0.28 (0.18, 0.43), and the associated AUCs equal to 0.64 (0.57, 0.70) and 0.74 (0.69, 0.80), respectively.

Conclusions: This study identified a metabolic signature reflecting a healthy lifestyle pattern which was inversely associated with HCC risk. The metabolic profile displayed a stronger association with HCC than did the modified HLI derived from questionnaire data. Measuring a specific panel of metabolites may identify strata of the population at higher risk for HCC and can add substantial discrimination compared with questionnaire data. This trial was registered at clinicaltrials.gov as NCT03356535.

Place, publisher, year, edition, pages
American Society for Nutrition, 2018
Keywords
hepatocellular carcinoma, targeted metabolomics, multivariate statistics, metabolic signatures, partial least squares, healthy lifestyle index, EPIC
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:umu:diva-150027 (URN)10.1093/ajcn/nqy074 (DOI)000438059600014 ()29924298 (PubMedID)2-s2.0-85050796927 (Scopus ID)
Available from: 2018-07-03 Created: 2018-07-03 Last updated: 2018-08-10Bibliographically approved
Rentschler, G., Rodushkin, I., Cerna, M., Chen, C., Harari, F., Harari, R., . . . Bergdahl, I. A. (2018). Platinum, palladium, rhodium, molybdenum and strontium in blood of urban women in nine countries. International journal of hygiene and environmental health (Print), 221(2), 223-230
Open this publication in new window or tab >>Platinum, palladium, rhodium, molybdenum and strontium in blood of urban women in nine countries
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2018 (English)In: International journal of hygiene and environmental health (Print), ISSN 1438-4639, E-ISSN 1618-131X, Vol. 221, no 2, p. 223-230Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: There is little reliable information on human exposure to the metals platinum (Pt), palladium (Pd) and rhodium (Rh), despite their use in enormous quantities in catalytic converters for automobile exhaust systems.

OBJECTIVES: To evaluate blood concentrations of Pt (B-Pt), Pd (B-Pd) and Rh (B-Rh) in women from six European and three non-European countries, and to identify potentially influential factors. In addition, molybdenum (Mo) and strontium (Sr) were analysed.

METHODS: Blood from 248 women aged 47-61 was analysed by high resolution inductively coupled plasma mass spectrometry under strict quality control.

RESULTS: The medians were: B-Pt 0.8 (range <0.6-5.2), B-Pd <5 (<5-9.3), B-Rh <0.4 (<0.4-3.6)ng/L and B-Mo 2.0 (0.2-16) and B-Sr 16.6 (3.5-49) μg/L. Two women with highly elevated B-Pt (242 and 60ng/L), previously cancer treated with cis-platinum, were not included in the data analysis. All elements varied geographically (2-3 times) (B-Pd P=0.05; all other elements P<0.001); variations within each area were generally 5-10 times. Traffic was not associated with increased concentrations.

CONCLUSIONS: General population blood concentrations of Pt, Pd and Rh are within or below the single digit ng/L range, much lower than in most previous reports. This is probably due to improved analytical performance, allowing for more reliable information at ultra-trace levels. In general, Mo and Sr agreed with previously reported concentrations. All elements showed geographical and inter-individual variations, but no convincing relationships with self-reported traffic intensity were found. Pt from the antineoplastic drug cis-platinum is retained in the body for years.

Place, publisher, year, edition, pages
Elsevier, 2018
Keywords
Biomarkers, Biomonitoring, Catalytic converters, Cis-platinum, High-resolution ICP-MS, Human, Metals, Traffic, Women
National Category
Occupational Health and Environmental Health
Identifiers
urn:nbn:se:umu:diva-141952 (URN)10.1016/j.ijheh.2017.10.017 (DOI)000429397300008 ()29126886 (PubMedID)
Available from: 2017-11-16 Created: 2017-11-16 Last updated: 2018-06-09Bibliographically approved
Sundkvist, A., Myte, R., Bodén, S., Enroth, S., Gyllensten, U., Harlid, S. & van Guelpen, B. (2018). Targeted plasma proteomics identifies a novel, robust association between cornulin and Swedish moist snuff. Scientific Reports, 8(1), Article ID 2320.
Open this publication in new window or tab >>Targeted plasma proteomics identifies a novel, robust association between cornulin and Swedish moist snuff
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2018 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, no 1, article id 2320Article in journal (Refereed) Published
Abstract [en]

Lifestyle behaviors are believed to influence the body's inflammatory state. Chronic low-grade inflammation contributes to the development of major non-communicable diseases such as diabetes, cardiovascular disease and cancer. Inflammation may thus be an important link between lifestyle and disease. We evaluated self-reported physical activity, tobacco use and alcohol consumption in relation to plasma levels of 160 validated inflammatory and cancer biomarkers. The study included 138 participants from a population-based cohort, all with repeated sampling of plasma and data ten years apart, allowing consideration of both intra- and inter-individual variation. Of 17 relationships identified, the strongest was an independent, positive association between cornulin (CRNN) and Swedish moist snuff (snus) use. We replicated the finding in a second cohort of 501 individuals, in which a dose-response relationship was also observed. Snus explained approximately one fifth of the variance in CRNN levels in both sample sets (18% and 23%). In conclusion, we identified a novel, independent, dose-dependent association between CRNN and snus use. Further study is warranted, to evaluate the performance of CRNN as a potential snus biomarker. The putative importance of lifestyle behaviors on a wide range of protein biomarkers illustrates the need for more personalized biomarker cut-offs.

Place, publisher, year, edition, pages
London: Nature Publishing Group, 2018
National Category
Public Health, Global Health, Social Medicine and Epidemiology Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-145046 (URN)10.1038/s41598-018-20794-3 (DOI)29396534 (PubMedID)
Available from: 2018-02-19 Created: 2018-02-19 Last updated: 2018-06-09Bibliographically approved
Pawlas, N., Strömberg, U., Carlberg, B., Cerna, M., Harari, F., Harari, R., . . . Bergdahl, I. A. (2013). Cadmium, mercury and lead in blood of urban women in Croatia, the Czech Republic, Poland, Slovakia, Slovenia, Sweden, China, Ecuador and Morocco. International Journal of Occupational Medicine and Environmental Health, 26(1), 58-72
Open this publication in new window or tab >>Cadmium, mercury and lead in blood of urban women in Croatia, the Czech Republic, Poland, Slovakia, Slovenia, Sweden, China, Ecuador and Morocco
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2013 (English)In: International Journal of Occupational Medicine and Environmental Health, ISSN 1232-1087, E-ISSN 1896-494X, Vol. 26, no 1, p. 58-72Article in journal (Refereed) Published
Abstract [en]

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.

Keywords
Cadmium, Mercury, Lead, Blood, Urban Women, European cities, Non-European Cities
National Category
Occupational Health and Environmental Health
Identifiers
urn:nbn:se:umu:diva-71115 (URN)10.2478/S13382-013-0071-9 (DOI)000317428800006 ()
Available from: 2013-05-21 Created: 2013-05-20 Last updated: 2018-06-08Bibliographically approved
Marklund Sundkvist, A., Olofsson, U. & Haglund, P. (2010). Organophosphorus flame retardants and plasticizers in marine and fresh water biota and in human milk. Journal of Environmental Monitoring, 12(4), 943-951
Open this publication in new window or tab >>Organophosphorus flame retardants and plasticizers in marine and fresh water biota and in human milk
2010 (English)In: Journal of Environmental Monitoring, ISSN 1464-0325, E-ISSN 1464-0333, Vol. 12, no 4, p. 943-951Article in journal (Refereed) Published
Abstract [en]

The levels and relative proportions of 11 organophosphorus flame retardants and plasticizers (OPs), some of which are reportedly toxic to aquatic organisms, were investigated in human breast milk and samples of fish and mussels from Swedish lakes and coastal areas in order to assess spatial differences in environmental exposure and spatial and temporal differences in human exposure. Some of the biota samples were collected at locations with known potential sources of OPs, but most were collected in background locations. Tris-2-chloroisopropyl phosphate (TCPP) and triphenyl phosphate (TPP) dominated in the biota with levels ranging from 170 to 770 ng g-1 for TCPP in perch and between 21 and 180 ng g-1 for TPP. In milk samples, TCPP (median 45 ng g-1) and tributyl phosphate (median 12 ng g(-1)) were the most frequently occurring OPs. Among samples of fish from background locations, the concentrations and profiles of most OPs were quite similar, indicating that their sources were diffuse. However, in fish from sample locations near known sources, there were marked differences in OP concentrations and profiles. Fish from a stream receiving surface water from Arlanda airport displayed high levels of OPs (10 200 ng g-1) that are commonly used in aircraft hydraulic fluids. Fish collected at points 1 or 2 km downstream of sewage treatment plants showed significantly higher levels of tris(2-butoxyethyl) phosphate (TBEP), one of the most typically abundant OP in effluents from such plants. In the milk samples obtained from women in different towns no distinct differences were detected in OP concentrations or profiles. However, the levels of TBEP tended to be higher in milk collected 10 years ago than in milk collected more recently. However, human exposure to OPs through eating fish or to breastfeeding babies seems to be of minor importance in relation to other potential sources, such as indoor dust inhalation and ingestion.

Identifiers
urn:nbn:se:umu:diva-33267 (URN)10.1039/b921910b (DOI)000276532100018 ()20383376 (PubMedID)
Available from: 2010-04-20 Created: 2010-04-20 Last updated: 2019-04-09Bibliographically approved
Klemmensen, B., Pedersen, S., Rydén, L., Dirckinck-Holmfeld, K. R. & Marklund, A. (2007). Environmental Policy: Legal and Economic Instruments (1ed.). Uppsala: The Baltic University Press
Open this publication in new window or tab >>Environmental Policy: Legal and Economic Instruments
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2007 (English)Book (Other academic)
Place, publisher, year, edition, pages
Uppsala: The Baltic University Press, 2007. p. 271 Edition: 1
Series
The Baltic University Environmental Management book series ; 1
Keywords
Social Sciences, Law, Law And Society, Samhällsvetenskap, Juridik, Juridik Och Samhälle, Political Science, Public Administration Studies, Statsvetenskap, Studier Av Offentlig Förvaltning, Economics And Business, Business Administration, Ekonomi Och Näringsliv, Företagsekonomi, Natural Sciences, Earth And Related Environmental Sciences, Environmental Sciences, Naturvetenskap, Geovetenskap Och Miljövetenskap, Miljövetenskap, Business, Eu Regulation, Licensing, Inspection, Taxes, Fees, Emissions Trading
National Category
Environmental Sciences
Identifiers
urn:nbn:se:umu:diva-126142 (URN)9789197552608 (ISBN)
Available from: 2016-09-29 Created: 2016-09-29 Last updated: 2018-06-07
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