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  • 1. Adlard, B.
    et al.
    Donaldson, S. G.
    Odland, J. O.
    Weihe, P.
    Berner, J.
    Carlsen, A.
    Bonefeld-Jorgensen, E. C.
    Dudarev, A. A.
    Gibson, J. C.
    Krümmel, E. M.
    Olafsdottir, K.
    Abass, K.
    Rautio, A.
    Bergdahl, Ingvar A.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Mulvad, G.
    Future directions for monitoring and human health research for the Arctic Monitoring and Assessment Programme2018In: Global Health Action, ISSN 1654-9716, E-ISSN 1654-9880, Vol. 11, no 1, article id 1480084Article in journal (Refereed)
    Abstract [en]

    For the last two and a half decades, a network of human health experts under the Arctic Monitoring and Assessment Program (AMAP) has produced several human health assessment reports. These reports have provided a base of scientific knowledge regarding environmental contaminants and their impact on human health in the Arctic. These reports provide scientific information and policy-relevant recommendations to Arctic governments. They also support international agreements such as the Stockholm Convention on Persistent Organic Pollutants (POPs) and the Minamata Convention on Mercury. Key topics discussed in this paper regarding future human health research in the circumpolar Arctic are continued contaminant biomonitoring, health effects research and risk communication. The objective of this paper is to describe knowledge gaps and future priorities for these fields.

  • 2. Akesson, Agneta
    et al.
    Barregard, Lars
    Bergdahl, Ingvar A.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Nordberg, Gunnar F.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Nordberg, Monica
    Skerfving, Staffan
    Non-Renal Effects and the Risk Assessment of Environmental Cadmium Exposure2014In: Journal of Environmental Health Perspectives, ISSN 0091-6765, E-ISSN 1552-9924, Vol. 122, no 5, p. 431-438Article in journal (Refereed)
    Abstract [en]

    Background: Exposure to cadmium (Cd) has long been recognized as a health hazard, both in industry and in general populations with high exposure. Under the currently prevailing health risk assessment, the relationship between urinary Cd (U-Cd) concentrations and tubular proteinuria is used. However, doubts have recently been raised regarding the justification of basing the risk assessment on this relationship at very low exposure. Objectives: Our objective was to review available information on health effects of Cd exposure with respect to human health risk assessment. Discussion: The associations between U-Cd and urinary proteins at very low exposure may not be due to Cd toxicity, and the clinical significance of slight proteinuria may also be limited. More importantly, other effects have been reported at very low Cd exposure. There is reason to challenge the basis of the existing health risk assessment for Cd. Our review of the literature found that exposure to low concentrations of Cd is associated with effects on bone, including increased risk of osteoporosis and fractures, and that this observation has implications for the health risk assessment of Cd. Other effects associated with Cd should also be considered, in particular cancer, although the information is still too limited for appropriate use in quantitative risk assessment. Conclusion: Non-renal effects should be considered critical effects in the health risk assessment of Cd.

  • 3.
    Anticona, Cynthia
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Bergdahl, Ingvar A
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Lundh, Thomas
    Alegre, Yuri
    Sebastian, Miguel San
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Lead exposure in indigenous communities of the Amazon basin, Peru2011In: International journal of hygiene and environmental health (Print), ISSN 1438-4639, E-ISSN 1618-131X, Vol. 215, no 1, p. 59-63Article in journal (Refereed)
    Abstract [en]

    Since 2006, three studies have reported elevated levels of lead (Pb) among the indigenous population of the Corrientes river, in the Amazon basin of Peru. Due to the large evidence of environmental pollution related to oil exploitation in the area, this activity has been suggested as the source of exposure. This study aimed to evaluate Pb levels in the population and environment of two communities exposed and one community non-exposed to the oil exploitation activity. Blood lead levels (BLL) were determined by the instrument Leadcare. A comparison with the graphite furnace atomic absorption technique was performed in order to validate the Leadcare results. Environmental samples were analyzed by inductively coupled plasma atomic emission spectroscopy. Among 361 capillary samples, the mean BLL was 9.4μg/dl. Mean BLL of the communities exposed (n=171, x¯=9.5μg/dl) and non-exposed (n=190, x¯=9.2μg/dl) to the oil activity were not significantly different. Pb levels in environmental samples were below the maximum permissible levels. The sources of exposure could not be identified. Elevated levels of Pb in the oil-non-exposed community pointed out at other sources not yet clarified.

  • 4.
    Anticona, Cynthia
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Bergdahl, Ingvar A
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    San Sebastian, Miguel
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Lead exposure among children from native communities of the Peruvian Amazon basin2012In: Revista panamericana de salud pùblica, ISSN 1020-4989, E-ISSN 1680-5348, Vol. 31, no 4, p. 296-302Article in journal (Refereed)
    Abstract [en]

    Objective. To assess potential risk factors associated with elevated blood lead levels (BLLs) among children in two communities from the Corrientes River basin in the Peruvian Amazon.

    Methods. Children aged 0-17 years were screened for BLLs, hemoglobin levels, and anthropometric measures. Dwelling, family, and child data were collected through a parental questionnaire. Statistical analysis included descriptive and bivariate analysis. Multiple linear and logistic regressions using generalized estimating equations were also conducted to determine associated risk factors. A map of each community was drawn to examine the spatial distribution of BLLs.

    Results. Of 208 children (88 from 23 households of the Peruanito community and 120 from 28 households of Santa Isabel), 27.4% had BLLs >= 10 mu g/dL. The geometric mean (+/- standard deviation) BLL was 8.7 +/- 4.0 mu g/dL (range 3.0-26.8 mu g/dL). In the total population, linear regression analysis indicated that age was positively associated with BLLs (P < 0.05). Logistic regression analysis showed that boys had 2.12 times greater odds of having BLLs >= 10 mu g/dL than girls (P < 0.05). Among the children 0-3 years, those whose mothers had BLLs >= 10 mu g/dL had 45.0% higher odds of presenting BLLs >= 10 mu g/dL than children whose mothers had BLLs < 10 mu g/dL (P < 0.05).

    Conclusions. Older age, male gender, and mothers' BLL >= 10 mu g/dL were the main risk factors for elevated BLLs. The higher risk in boys 7-17 years suggests that exposure could be related to specific activities in this group, such as fishing and hunting. Continuous monitoring of BLLs in the Corrientes River population is recommended.

  • 5.
    Anticona, Cynthia
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Bergdahl, Ingvar
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    San Sebastian, Miguel
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Sources and risk factors for lead exposure in indigenous children of the Peruvian Amazon, disentangling connections with oil activity2012In: International journal of occupational and environmental health, ISSN 1077-3525, E-ISSN 2049-3967, Vol. 18, no 4, p. 268-277Article in journal (Refereed)
    Abstract [en]

    Introduction: In the Corrientes river basin, Peruvian Amazon, lead exposure among indigenous communities was first reported in 2006. To address controversy regarding the main source of exposure, this study aimed to identify the sources and risk factors for lead exposure among children from the communities in question, and to clarify the potential relationship with oil activity.Methods: This cross-sectional study was conducted in six communities. Participants were children aged 0–17 years and their mothers. Data collection included blood lead levels (BLLs) and hemoglobin determination, a questionnaire on risk factors and environmental sampling. We used age-stratified multivariate regression models, with generalized estimating equation to account for correlation within households.Results: Twenty-seven percent of the children had BLLs ≧10 μg/dl. Mother's BLLs ≧10 μg/dl, playing and chewing lead scraps, fishing ≧three times/week, and living in highly oil-exposed communities increased the risk of having BLLs ≧10 μg/dl. Lead concentrations in sediment, soil, dust, and fish samples were below reference values.Conclusions: Mother's BLLs ≧10 μg/dl, playing and chewing lead scraps to manufacture fishing sinkers were the most important risk factors for children’s BLLs ≧10 μg/dl. The connection with oil activity appears to be through access to metal lead from the industry's wastes.

  • 6.
    Anticona, Cynthia
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Coe, Anna-Britt
    Umeå University, Faculty of Social Sciences, Umeå Centre for Gender Studies (UCGS).
    Bergdahl, Ingvar
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    San Sebastian, Miguel
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Easier said than done: applying the Ecohealth principles to a study of heavy metals exposure among indigenous communities of the Peruvian Amazon2013In: BMC Public Health, ISSN 1471-2458, E-ISSN 1471-2458, Vol. 13, article id 437Article in journal (Refereed)
    Abstract [en]

    Background The renewed interest in community participation in health research is linked to its potential for bridging gaps between research and practice. Its main attributes are the generation of knowledge that can lead to socially robust, long-lasting solutions and the creation of a colearner relationship between researchers and research users. Following this philosophy, Ecohealth has evolved into a specialized framework for participatory research on the impact of pollution on ecosystems and human health. However, its principles pose considerable challenges. Its outcomes are strongly influenced by contextual factors that are impossible to control for ahead of time.

    This paper describes how the Ecohealth principles were applied to an epidemiological study of heavy metals exposure among indigenous communities of the Peruvian Amazon. It illustrates how knowledge generated from participatory research does not necessarily imply solving a public health problem. This study aimed to contribute to the understanding of the benefits and barriers of following the basic principles of the Ecohealth approach, and assist researchers working in similar contexts.

    Research process Based upon their personal experience as participant observers, the authors describe the research process; then, they discuss the most important challenges faced, their implications, and the attempted strategies for resolution.

    Challenges Challenges were grouped into four themes: (1) building trust; (2) one partnership, many stakeholders, multiple agendas; (3) being a researcher; and (4) communicating complex and unexpected findings.

    Conclusions Integrating the principles of transdisciplinarity and participation posed a series of challenges to the research process that were difficult, and sometimes impossible to overcome. However, positive outcomes from this experience were the lessons learned by the different actors. Despite the lack of immediate action, it is expected that useful interventions to prevent and control lead exposure in the Corrientes population will be implemented in the medium term.

  • 7.
    Bergdahl, I A
    et al.
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Occupational and Enviromental Medicine.
    Torén, K
    Eriksson, K
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Occupational and Enviromental Medicine.
    Hedlund, U
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Occupational and Enviromental Medicine.
    Nilsson, T
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Occupational and Enviromental Medicine.
    Flodin, R
    Järvholm, B
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Occupational and Enviromental Medicine.
    Increased mortality in COPD among construction workers exposed to inorganic dust.2004In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 23, no 3, p. 402-406Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to find out if occupational exposure to dust, fumes or gases, especially among never-smokers, increased the mortality from chronic obstructive pulmonary disease (COPD). A cohort of 317,629 Swedish male construction workers was followed from 1971 to 1999. Exposure to inorganic dust (asbestos, man-made mineral fibres, dust from cement, concrete and quartz), gases and irritants (epoxy resins, isocyanates and organic solvents), fumes (asphalt fumes, diesel exhaust and metal fumes), and wood dust was based on a job-exposure matrix. An internal control group with "unexposed" construction workers was used, and the analyses were adjusted for age and smoking. When all subjects were analysed, there was an increased mortality from COPD among those with any airborne exposure (relative risk 1.12 (95% confidence interval (CI) 1.03-1.22)). In a Poisson regression model, including smoking, age and the major exposure groups, exposure to inorganic dust was associated with an increased risk (hazard ratio (HR) 1.10 (95% CI 1.06-1.14)), especially among never-smokers (HR 2.30 (95% CI 1.07-4.96)). The fraction of COPD among the exposed attributable to any airborne exposure was estimated as 10.7% overall and 52.6% among never-smokers. In conclusion, occupational exposure among construction workers increases mortality due to chronic obstructive pulmonary disease, even among never-smokers.

  • 8.
    Bergdahl, Ingvar
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Biomonitoring of metals: Analysis, non-linearity, possible artefacts, and genetics2012In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 211, p. S12-S12Article in journal (Refereed)
  • 9.
    Bergdahl, Ingvar
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    If there is an effect of lead exposure on malaria, then the activity of delta-aminolevulinate dehydratase (ALAD) may play a role, as ALAD is imported by the parasite from the host2009In: International journal of hygiene and environmental health (Print), ISSN 1438-4639, E-ISSN 1618-131X, Vol. 212, no 4, p. 445-446Article in journal (Refereed)
  • 10.
    Bergdahl, Ingvar A
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Occupational and Enviromental Medicine.
    Another fundamental error in "What is the meaning of non-linear dose-response relationships between blood lead concentrations and IQ?" became obvious in the authors' response to comments.2007In: Neurotoxicology, ISSN 0161-813X, E-ISSN 1872-9711, Vol. 28, no 3, p. 705-6; author reply 706Article in journal (Refereed)
  • 11.
    Bergdahl, Ingvar A
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Occupational and Enviromental Medicine.
    What is the meaning of non-linear dose-response relationships between blood lead concentrations and IQ?2006In: Neurotoxicology, ISSN 0161-813X, Vol. 27, no 6, p. 1125-Article in journal (Refereed)
  • 12.
    Bergdahl, Ingvar A.
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Ahlqwist, Margareta
    Department of Oral and Maxillofacial Radiology, The Sahlgrenska Academy, University of Gothenburg.
    Barregard, Lars
    Department of Occupational and Environmental Medicine, The Sahlgrenska Academy, University of Gothenburg.
    Björkelund, Cecilia
    Department of Public Health and Community Medicine/Primary Health Care, The Sahlgrenska Academy, University of Gothenburg.
    Blomstrand, Ann
    Department of Public Health and Community Medicine/Primary Health Care, The Sahlgrenska Academy, University of Gothenburg.
    Skerfving, Staffan
    Division of Occupational and Environmental Medicine, Lund University.
    Sundh, Valter
    Department of Public Health and Community Medicine, The Sahlgrenska Academy, University of Gothenburg.
    Wennberg, Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Lissner, Lauren
    Department of Public Health and Community Medicine, The Sahlgrenska Academy, University of Gothenburg .
    Mercury in serum predicts low risk of death and myocardial infarction in Gothenburg women2013In: International Archives of Occupational and Environmental Health, ISSN 0340-0131, E-ISSN 1432-1246, Vol. 86, no 1, p. 71-77Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Markers of mercury (Hg) exposure have shown both positive and negative associations with cardiovascular disease (CVD). We assessed the association between serum Hg (S-Hg) and risk of cardiovascular disease in a prospective population-based cohort, with attention to the roles of dental health and fish consumption.

    METHODS: Total mortality, as well as morbidity and mortality from acute myocardial infarction (AMI) and stroke, was followed up for 32 years in 1,391 women (initially age 38-60), in relation to S-Hg at baseline, using Cox regression models. Potential confounders (age, socioeconomic status, serum lipids, alcohol consumption, dental health, smoking, hypertension, waist-hip ratio, and diabetes) and other covariates (e.g., fish consumption) were also considered.

    RESULTS: Hazard ratios (HR) adjusted only for age showed strong inverse associations between baseline S-Hg and total mortality [highest quartile: hazard ratio (HR) 0.76; 95% confidence interval (CI) 0.59-0.97], incident AMI (HR 0.56; CI 0.34-0.93), and fatal AMI (HR 0.31; CI 0.15-0.66). Adjustment for potential confounding factors, especially dental health, had a strong impact on the risk estimates, and after adjustment, only the reduced risk of fatal AMI remained statistically significant.

    CONCLUSIONS: There was a strong inverse association between Hg exposure and CVD. Likely, reasons are confounding with good dental health (also correlated with the number of amalgam fillings in these age groups) and/or fish consumption. The results suggest potential effects of dental health and/or fish consumption on CVD that deserve attention in preventive medicine.

  • 13.
    Bergdahl, Ingvar A
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Gerhardsson, Lars
    Liljelind, Ingrid E
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Nilsson, Leif
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Skerfving, Staffan
    Plasma-lead concentration: investigations into its usefulness for biological monitoring of occupational lead exposure2006In: American Journal of Industrial Medicine, ISSN 0271-3586, E-ISSN 1097-0274, Vol. 49, no 2, p. 93-101Article in journal (Refereed)
    Abstract [en]

    Background: The lead concentration in plasma is correlated to that in whole blood with a two to fourfold variation. It has never been investigated if this variation is inter-individual.

    Methods: Lead and hemoglobin were determined in blood and plasma from 13 lead workers with a history of relatively high blood-lead concentrations, sampled three times during 1 day. The variation in the distribution of lead between cells and plasma was studied, but not the variation in the lead concentrations as such.

    Results: Blood hemoglobin decreased with rising plasma lead (0.9–3.0 µg/L). Regarding the distribution of lead, no effect of current exposure during the day or of recent meals appeared. As much as 84% of the overall variance of the distribution of lead between cells and plasma could be attributed to individual factors. After adjustment for erythrocyte volume fraction this decreased to 67%. Plasma samples with elevated hemoglobin concentrations (due to in vitro hemolysis) had somewhat elevated lead concentrations.

    Conclusions: Plasma lead is not significantly altered by variation in a single day's exposure and, therefore, the choice of time of the day is not critical for sampling. However, plasma lead is negatively correlated to blood hemoglobin and mild hemolysis (not visible by the eye) in a sample may increase plasma lead with up to 30%. Finally, plasma provides lead exposure information that differs from whole blood, but it is not clear which one of these is the biomarker with the closest relation to exposure and/or effects.

  • 14.
    Bergdahl, Ingvar A.
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Human biobanks in research: recent studies of health effects of metals, and plans for persistent organic pollutants. Experiences and plans in northern Sweden2013In: International Journal of Circumpolar Health, ISSN 1239-9736, E-ISSN 2242-3982, Vol. 72, no Supplement 1, p. 997-997Article in journal (Refereed)
  • 15.
    Bergdahl, Ingvar A
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Jonsson, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Eriksson, Kåre
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Damber, Lena
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Järvholm, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Lung cancer and exposure to quartz and diesel exhaust in Swedish iron ore miners with concurrent exposure to radon2010In: Occupational and Environmental Medicine, ISSN 1351-0711, E-ISSN 1470-7926, Vol. 67, no 8, p. 513-518Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Studies of underground miners have documented an increased risk of lung cancer mainly linked to radon exposure but possibly influenced by other concurrent exposures. METHODS: A cohort study was carried out in 8321 iron ore miners with low exposure to radon, employed in 1923-1998 and followed up for lung cancer in 1958-2000. Historical exposures to radon, crystalline silica and diesel exhaust were assessed. Data including exposure to radon, quartz and diesel exhaust from another mine with higher exposure to radon were reanalysed. RESULTS: Miners had increased risk for lung cancer (SIR 1.48 (95% CI 1.22 to 1.78), based on 112 cases during 227,000 person-years). The increased risk could not be explained by exposure to radon or diesel exhaust but was associated with exposure to crystalline silica: SIR 0.96 (0.53 to 1.62), 1.45 (1.10 to 1.87), 1.99 (1.31 to 2.90) and 1.77 (0.92 to 3.10) in groups with exposure to 0, 0-2, 2-5 and >5 mg years/m3, respectively. Reanalysis of data from the other mine indicated that quartz was a possible confounder in the analysis of relationship between radon and lung cancer. In the highest radon exposed group, the point estimate for the RR decreased from 5.65 to 3.90 when adjusting for concurrent exposure to quartz. CONCLUSIONS: Crystalline silica, a known carcinogen, probably affects lung cancer risk in iron ore miners. The main implication of the results is for interpretation of the dose-response curve for radon and lung cancer in underground iron ore miners. Since exposure to radon and quartz is often correlated, quartz exposure can be an important confounder.

  • 16.
    Bergdahl, Ingvar A
    et al.
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Occupational and Enviromental Medicine.
    Skerfving, Staffan
    Biomonitoring of lead exposure-alternatives to blood.2008In: Journal of Toxicology and Environmental Health, ISSN 1528-7394, E-ISSN 1087-2620, Vol. 71, no 18, p. 1235-43Article in journal (Refereed)
    Abstract [en]

    Lead ( Pb) is one of the most important models for biomonitoring of exposure, with the blood Pb concentration as a predominant choice in practice and in epidemiology. In this article the alternatives for biomarkers to blood are reviewed. This overview focuses on a number of different qualities that are of importance in the evaluation of a biomarker's usefulness and performance. The qualities scrutinized included: (1) analytical accuracy and precision; (2) cost; (3) practical issues; (4) what is reflected by the biomarker; (5) relationship to exposure; and (6) relationship to effects. Data indicate that the best biomarker in some circumstances may be blood, but bone or teeth (for past exposures), feces (for current gastrointestinal exposure), or urine (for organic Pb) are sometimes more useful. A striking feature is that no generally accepted biomarker of bioavailable Pb exists, though plasma, bone, teeth, urine, and hair have all been discussed. For one of the most used applications of blood Pb, monitoring of lead workers' exposure, blood has important shortcomings in that it shows a poor response to changes in exposure at high levels. The alternative of plasma has not been sufficiently evaluated to be considered an alternative in occupational health services, although previous analytical problems are basically overcome. Possibly, urine deserves also more attention. Almost all biomarkers lack systematic data on variation within and between individuals.

  • 17.
    Bergdahl, Ingvar
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Torén, K
    Nilsson, Tohr
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Eriksson, Kåre
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Hedlund, U
    Flodin, R
    Järvholm, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Increased mortality in COPD among construction workers exposed to inorganic dust: from the authors2004In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 24, no 3, p. 512-512Article in journal (Refereed)
  • 18. Berger, Eloise
    et al.
    Delpierre, Cyrille
    Hosnijeh, Fatemeh Saberi
    Kelly-Irving, Michelle
    Portengen, Lutzen
    Bergdahl, Ingvar
    Umeå University, Faculty of Medicine, Department of Biobank Research.
    Johansson, Ann Sofie
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Krogh, Vittorio
    Palli, Domenico
    Panico, Salvatore
    Sacerdote, Carlotta
    Tumino, Rosario
    Kyrtopoulos, Soterios A.
    Vineis, Paolo
    Chadeau-Hyam, Marc
    Vermeulen, Roel
    Castagné, Raphaële
    Association between low-grade inflammation and Breast cancer and B-cell Myeloma and Non-Hodgkin Lymphoma: findings from two prospective cohorts2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 10805Article in journal (Refereed)
    Abstract [en]

    Chronic inflammation may be involved in cancer development and progression. Using 28 inflammatory-related proteins collected from prospective blood samples from two case-control studies nested in the Italian component of the European Prospective Investigation into Cancer and nutrition (n = 261) and in the Northern Sweden Health and Disease Study (n = 402), we tested the hypothesis that an inflammatory score is associated with breast cancer (BC) and.-cell Non-Hodgkin Lymphoma (B-cell NHL, including 68 multiple myeloma cases) onset. We modelled the relationship between this inflammatory score and the two cancers studied: (BC and B-cell NHL) using generalised linear models, and assessed, through adjustments the role of behaviours and lifestyle factors. Analyses were performed by cancer types pooling both populations, and stratified by cohorts, and time to diagnosis. Our results suggested a lower inflammatory score in B-cell NHL cases (β = -1.28, p = 0.012), and, to lesser, extent with BC (β= -0.96, p = 0.33) compared to controls, mainly driven by cancer cases diagnosed less than 6 years after enrolment. These associations were not affected by subsequent adjustments for potential intermediate confounders, notably behaviours. Sensitivity analyses indicated that our findings were not affected by the way the inflammatory score was calculated. These observations call for further studies involving larger populations, larger variety of cancer types and repeated measures of larger panel of inflammatory markers.

  • 19. Bohler, S.
    et al.
    Espín-Pérez, A.
    Gebel, S.
    Bergdahl, Ingvar
    Umeå University, Faculty of Medicine, Department of Biobank Research.
    Palli, D.
    Rantakokko, P.
    Kiviranta, H.
    Kyrtopoulos, S.
    Balling, R.
    Kleinjans, J. C. S.
    Genes associated with Parkinson's disease respond to increasing polychlorinated biphenyl levels in the blood of healthy females2018In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 295, p. S159-S160Article in journal (Other academic)
  • 20. Burstyn, I
    et al.
    Boffetta, P
    Järvholm, B
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine.
    Partanen, T
    Svane, O
    Langård, S
    Kauppinen, T
    Stücker, I
    Shaham, J
    Heederik, D
    Ahrens, W
    Bergdahl, I
    Cenée, S
    Hooiveld, M
    Randem, B G
    Johansen, C
    Ferro, G
    Kromhout, H
    Risk of fatal industrial accidents and death from other external causes among asphalt workers.2004In: Occup Environ Med, ISSN 1470-7926, Vol. 61, no 1, p. 86-8Article in journal (Refereed)
  • 21. Bárány, E
    et al.
    Bergdahl, I A
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Occupational and Enviromental Medicine.
    Bratteby, L-E
    Lundh, T
    Samuelson, G
    Skerfving, S
    Oskarsson, A
    Iron status influences trace element levels in human blood and serum.2005In: Environ Res, ISSN 0013-9351, Vol. 98, no 2, p. 215-23Article in journal (Refereed)
  • 22. Campanella, Gianluca
    et al.
    Gunter, Marc J.
    Polidoro, Silvia
    Krogh, Vittorio
    Palli, Domenico
    Panico, Salvatore
    Sacerdote, Carlotta
    Tumino, Rosario
    Fiorito, Giovanni
    Guarrera, Simonetta
    Iacoviello, Licia
    Bergdahl, Ingvar A.
    Umeå University, Faculty of Medicine, Department of Biobank Research.
    Melin, Beatrice
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    de Kok, Theo M. C. M.
    Georgiadis, Panagiotis
    Kleinjans, Jos C. S.
    Kyrtopoulos, Soterios A.
    Bueno-de-Mesquita, H. Bas
    Lillycrop, Karen A.
    May, Anne M.
    Onland-Moret, N. Charlotte
    Murray, Robert
    Riboli, Elio
    Verschuren, Monique
    Lund, Eiliv
    Mode, Nicolle
    Sandanger, Torkjel M.
    Fiano, Valentina
    Trevisan, Morena
    Matullo, Giuseppe
    Froguel, Philippe
    Elliott, Paul
    Vineis, Paolo
    Chadeau-Hyam, Marc
    Epigenome-wide association study of adiposity and future risk of obesity-related diseases2018In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 42, no 12, p. 2022-2035Article in journal (Refereed)
    Abstract [en]

    Background: Obesity is an established risk factor for several common chronic diseases such as breast and colorectal cancer, metabolic and cardiovascular diseases; however, the biological basis for these relationships is not fully understood. To explore the association of obesity with these conditions, we investigated peripheral blood leucocyte (PBL) DNA methylation markers for adiposity and their contribution to risk of incident breast and colorectal cancer and myocardial infarction.

    Methods: DNA methylation profiles (Illumina Infinium® HumanMethylation450 BeadChip) from 1941 individuals from four population-based European cohorts were analysed in relation to body mass index, waist circumference, waist-hip and waist-height ratio within a meta-analytical framework. In a subset of these individuals, data on genome-wide gene expression level, biomarkers of glucose and lipid metabolism were also available. Validation of methylation markers associated with all adiposity measures was performed in 358 individuals. Finally, we investigated the association of obesity-related methylation marks with breast, colorectal cancer and myocardial infarction within relevant subsets of the discovery population.

    Results: We identified 40 CpG loci with methylation levels associated with at least one adiposity measure. Of these, one CpG locus (cg06500161) in ABCG1 was associated with all four adiposity measures (P = 9.07×10−8 to 3.27×10−18) and lower transcriptional activity of the full-length isoform of ABCG1 (P = 6.00×10−7), higher triglyceride levels (P = 5.37×10−9) and higher triglycerides-to-HDL cholesterol ratio (P = 1.03×10−10). Of the 40 informative and obesity-related CpG loci, two (in IL2RB and FGF18) were significantly associated with colorectal cancer (inversely, P < 1.6×10−3) and one intergenic locus on chromosome 1 was inversely associated with myocardial infarction (P < 1.25×10−3), independently of obesity and established risk factors.

    Conclusion: Our results suggest that epigenetic changes, in particular altered DNA methylation patterns, may be an intermediate biomarker at the intersection of obesity and obesity-related diseases, and could offer clues as to underlying biological mechanisms.

  • 23. Campanella, Gianluca
    et al.
    Gunter, Marc J.
    Polidoro, Silvia
    Krogh, Vittorio
    Palli, Domenico
    Panico, Salvatore
    Sacerdote, Carlotta
    Tumino, Rosario
    Fiorito, Giovanni
    Guarrera, Simonetta
    Iacoviello, Licia
    Bergdahl, Ingvar
    Umeå University, Faculty of Medicine, Department of Biobank Research.
    Melin, Beatrice
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    de Kok, Theo M. C. M.
    Georgiadis, Panagiotis
    Kleinjans, Jos C. S.
    Kyrtopoulos, Soterios A.
    Bueno-de-Mesquita, H. Bas
    Lillycrop, Karen A.
    May, Anne M.
    Onland-Moret, N. Charlotte
    Murray, Robert
    Riboli, Elio
    Verschuren, Monique
    Lund, Eiliv
    Mode, Nicolle
    Sandanger, Torkjel M.
    Fiano, Valentina
    Trevisan, Morena
    Matullo, Giuseppe
    Froguel, Philippe
    Elliott, Paul
    Vineis, Paolo
    Chadeau-Hyam, Marc
    Epigenome-wide association study of adiposity and future risk of obesity-related diseases2018In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 42, no 12, p. 2022-2035Article in journal (Refereed)
    Abstract [en]

    Background Obesity is an established risk factor for several common chronic diseases such as breast and colorectal cancer, metabolic and cardiovascular diseases; however, the biological basis for these relationships is not fully understood. To explore the association of obesity with these conditions, we investigated peripheral blood leucocyte (PBL) DNA methylation markers for adiposity and their contribution to risk of incident breast and colorectal cancer and myocardial infarction. Methods DNA methylation profiles (Illumina Infinium® HumanMethylation450 BeadChip) from 1941 individuals from four population-based European cohorts were analysed in relation to body mass index, waist circumference, waist-hip and waistheight ratio within a meta-analytical framework. In a subset of these individuals, data on genome-wide gene expression level, biomarkers of glucose and lipid metabolism were also available. Validation of methylation markers associated with all adiposity measures was performed in 358 individuals. Finally, we investigated the association of obesity-related methylation marks with breast, colorectal cancer and myocardial infarction within relevant subsets of the discovery population. Results We identified 40 CpG loci with methylation levels associated with at least one adiposity measure. Of these, one CpG locus (cg06500161) in ABCG1 was associated with all four adiposity measures (P=9.07×10−8 to 3.27×10−18) and lower transcriptional activity of the full-length isoform of ABCG1 (P=6.00×10−7), higher triglyceride levels (P=5.37×10−9) and higher triglycerides-to-HDL cholesterol ratio (P=1.03×10−10). Of the 40 informative and obesity-related CpG loci, two (in IL2RB and FGF18) were significantly associated with colorectal cancer (inversely, P<1.6×10−3) and one intergenic locus on chromosome 1 was inversely associated with myocardial infarction (P<1.25×10−3), independently of obesity and established risk factors. Conclusion Our results suggest that epigenetic changes, in particular altered DNA methylation patterns, may be an intermediate biomarker at the intersection of obesity and obesity-related diseases, and could offer clues as to underlying biological mechanisms.

  • 24. Chadeau-Hyam, M.
    et al.
    Vermeulen, R. C. H.
    Hebels, D. G. A. J.
    Castagne, R.
    Campanella, G.
    Portengen, L.
    Kelly, R. S.
    Bergdahl, Ingvar
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Melin, Beatrice
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Biobank Research. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Palli, D.
    Krogh, V.
    Tumino, R.
    Sacerdote, C.
    Panico, S.
    de Kok, T. M. C. M.
    Smith, M. T.
    Kleinjans, J. C. S.
    Vineis, P.
    Kyrtopoulos, S. A.
    Prediagnostic transcriptomic markers of Chronic lymphocytic leukemia reveal perturbations 10 years before diagnosis2014In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 25, no 5, p. 1065-1072Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    B-cell lymphomas are a diverse group of hematological neoplasms with differential etiology and clinical trajectories. Increased insights in the etiology and the discovery of prediagnostic markers have the potential to improve the clinical course of these neoplasms.

    METHODS:

    We investigated in a prospective study global gene expression in peripheral blood mononuclear cells of 263 incident B-cell lymphoma cases, diagnosed between 1 and 17 years after blood sample collection, and 439 controls, nested within two European cohorts.

    RESULTS:

    Our analyses identified only transcriptomic markers for specific lymphoma subtypes; few markers of multiple myeloma (N = 3), and 745 differentially expressed genes in relation to future risk of chronic lymphocytic leukemia (CLL). The strongest of these associations were consistently found in both cohorts and were related to (B-) cell signaling networks and immune system regulation pathways. CLL markers exhibited very high predictive abilities of disease onset even in cases diagnosed more than 10 years after blood collection.

    CONCLUSIONS:

    This is the first investigation on blood cell global gene expression and future risk of B-cell lymphomas. We mainly identified genes in relation to future risk of CLL that are involved in biological pathways, which appear to be mechanistically involved in CLL pathogenesis. Many but not all of the top hits we identified have been reported previously in studies based on tumor tissues, therefore suggesting that a mixture of preclinical and early disease markers can be detected several years before CLL clinical diagnosis.

  • 25. Chatziioannou, Aristotelis
    et al.
    Georgiadis, Panagiotis
    Hebels, Dennie G
    Liampa, Irene
    Valavanis, Ioannis
    Bergdahl, Ingvar A
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Palli, Domenico
    Chadeau-Hyam, Marc
    Siskos, Alexandros P
    Keun, Hector
    Botsivali, Maria
    de Kok, Theo M C M
    Pérez, Almudena Espín
    Kleinjans, Jos C S
    Vineis, Paolo
    Kyrtopoulos, Soterios A
    Blood-based omic profiling supports female susceptibility to tobacco smoke-induced cardiovascular diseases2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 42870Article in journal (Refereed)
    Abstract [en]

    We recently reported that differential gene expression and DNA methylation profiles in blood leukocytes of apparently healthy smokers predicts with remarkable efficiency diseases and conditions known to be causally associated with smoking, suggesting that blood-based omic profiling of human populations may be useful for linking environmental exposures to potential health effects. Here we report on the sex-specific effects of tobacco smoking on transcriptomic and epigenetic features derived from genome-wide profiling in white blood cells, identifying 26 expression probes and 92 CpG sites, almost all of which are affected only in female smokers. Strikingly, these features relate to numerous genes with a key role in the pathogenesis of cardiovascular disease, especially thrombin signaling, including the thrombin receptors on platelets F2R (coagulation factor II (thrombin) receptor; PAR1) and GP5 (glycoprotein 5), as well as HMOX1 (haem oxygenase 1) and BCL2L1 (BCL2-like 1) which are involved in protection against oxidative stress and apoptosis, respectively. These results are in concordance with epidemiological evidence of higher female susceptibility to tobacco-induced cardiovascular disease and underline the potential of blood-based omic profiling in hazard and risk assessment.

  • 26. Chen, Xiao
    et al.
    Zhu, Guoying
    Jin, Taiyi
    Akesson, Agneta
    Bergdahl, Ingvar A
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Occupational and Enviromental Medicine.
    Lei, Lijian
    Weng, Shifang
    Liang, Yihuai
    Changes in bone mineral density 10 years after marked reduction of cadmium exposure in a Chinese population.2009In: Environmental research, ISSN 1096-0953, Vol. 109, no 7, p. 874-9Article in journal (Refereed)
    Abstract [en]

    The main focus of this study was to evaluate the long-term effects of Cd on forearm bone mineral density after the cessation of the ingestion of Cd-polluted rice. A total of 458 persons (294 women, 164 men) from three Cd exposure areas (low, moderately, and heavy) participated in this study. Those living in the moderate and heavy exposure areas ceased ingesting Cd-polluted rice (0.51 and 3.7mg/kg, respectively) in 1996 (10 years prior to present analysis). The participants completed a questionnaire and bone mineral density (BMD) was measured by dual energy X-ray absorptiometry (DXA) at the proximal radius and ulna. The changes and change percentage in forearm bone density and the prevalence of osteoporosis between 1998 and 2006 were used as markers of bone recovery. The Cd concentrations in urine (UCd) and blood (BCd) in 1998 were used as Cd exposure markers. The values of the BMD change and change percentage of groups in which UCd was above 5microg/g creatinine (microg/g crea) and BCd was above 10microg/L were significantly higher than those of the low-exposure groups (in women, p<0.001; in men, p>0.05). The BMD change and change percentage correlated positively with the UCd and BCd (in women, p<0.01; in men, p>0.05). Analysis of the Z-score revealed that the prevalence of osteoporosis in 2006 was higher than that in 1998 and increased along with the level of UCd and BCd in both women and men, especially for those subjects with the higher BCd [BCd>5microg/L, OR=3.45 (0.95-13.6); BCd>10microg/L, OR=4.51(1.57-13.54)] and UCd [UCd>10microg/g crea, OR=4.74 (1.82-12.81)] in women. It is concluded that decreasing dietary cadmium exposure at the population level is not associated with bone recovery at the individual level, and the adverse bone effects of Cd exposure persisted after the main source of Cd exposure had been blocked, especially in women.

  • 27. de Mello, Vanessa D.
    et al.
    Paananen, Jussi
    Lindström, Jaana
    Lankinen, Maria A.
    Shi, Lin
    Kuusisto, Johanna
    Pihlajamäki, Jussi
    Auriola, Seppo
    Lehtonen, Marko
    Rolandsson, Olov
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Bergdahl, Ingvar A.
    Umeå University, Faculty of Medicine, Department of Biobank Research.
    Nordin, Elise
    Ilanne-Parikka, Pirjo
    Keinänen-Kiukaanniemi, Sirkka
    Landberg, Rikard
    Eriksson, Johan G.
    Tuomilehto, Jaakko
    Hanhineva, Kati
    Uusitupa, Matti
    Indolepropionic acid and novel lipid metabolites are associated with a lower risk of type 2 diabetes in the Finnish Diabetes Prevention Study2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 46337Article in journal (Refereed)
    Abstract [en]

    Wide-scale profiling technologies including metabolomics broaden the possibility of novel discoveries related to the pathogenesis of type 2 diabetes (T2D). By applying non-targeted metabolomics approach, we investigated here whether serum metabolite profile predicts T2D in a well-characterized study population with impaired glucose tolerance by examining two groups of individuals who took part in the Finnish Diabetes Prevention Study (DPS); those who either early developed T2D (n = 96) or did not convert to T2D within the 15-year follow-up (n = 104). Several novel metabolites were associated with lower likelihood of developing T2D, including indole and lipid related metabolites. Higher indolepropionic acid was associated with reduced likelihood of T2D in the DPS. Interestingly, in those who remained free of T2D, indolepropionic acid and various lipid species were associated with better insulin secretion and sensitivity, respectively. Furthermore, these metabolites were negatively correlated with low-grade inflammation. We replicated the association between indolepropionic acid and T2D risk in one Finnish and one Swedish population. We suggest that indolepropionic acid, a gut microbiota-produced metabolite, is a potential biomarker for the development of T2D that may mediate its protective effect by preservation of alpha-cell function. Novel lipid metabolites associated with T2D may exert their effects partly through enhancing insulin sensitivity.

  • 28. Donat-Vargas, Carolina
    et al.
    Bergdahl, Ingvar A.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Tornevi, Andreas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Wennberg, Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Sommar, Johan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Koponen, Jani
    Kiviranta, Hannu
    Åkesson, Agneta
    Associations between repeated measure of plasma perfluoroalkyl substances and cardiometabolic risk factors2019In: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 124, p. 58-65Article in journal (Refereed)
    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.

  • 29. Donat-Vargas, Carolina
    et al.
    Bergdahl, Ingvar
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Tornevi, Andreas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Wennberg, Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Sommar, Johan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Kiviranta, Hannu
    Koponen, Jani
    Rolandsson, Olov
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Akesson, Agneta
    Perfluoroalkyl substances and risk of type II diabetes: A prospective nested case-control study2019In: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 123, p. 390-398Article in journal (Refereed)
    Abstract [en]

    Background: Perfluoroalkyl substances (PFAS) have drawn much attention due to bioaccumulation potential and their current omnipresence in human blood. We assessed whether plasma PFAS, suspected to induce endocrine-disrupting effects, were prospectively associated with clinical type 2 diabetes (T2D) risk.

    Methods: We established a nested case-control study within the Swedish prospective population-based Västerbotten Intervention Programme cohort. Several PFAS were measured in plasma from a subset of 124 case-control pairs at baseline (during 1990–2003) and at 10-year follow-up. T2D cases were matched (1:1) according to gender, age and sample date with participants without T2D (controls).

    Conditional logistic regressions were used to prospectively assess risk of T2D by baseline PFAS plasma concentrations. Associations between long-term PFAS plasma levels (mean of baseline and follow-up) and insulin resistance (HOMA2-IR) and beta-cell function (HOMA2-B%) at follow-up were prospectively explored among 178 and 181 controls, respectively, by multivariable linear regressions.

    Results: After adjusting for gender, age, sample year, diet and body mass index, the odds ratio of T2D for the sum of PFAS (Σ z-score PFAS) was 0.52 (95% confidence interval, CI: 0.20, 1.36), comparing third with first tertile; and 0.92 (95% CI: 0.84, 1.00) per one standard deviation increment of sum of log-transformed PFAS. Among the controls, the adjusted β of HOMA2-IR and HOMA-B% for the sum of PFAS were −0.26 (95% CI: −0.52, −0.01) and −9.61 (95% CI: −22.60, 3.39) respectively comparing third with first tertile.

    Conclusions: This prospective nested case-control study yielded overall inverse associations between individual PFAS and risk of T2D, although mostly non-significant. Among participants without T2D, long-term PFAS exposure was prospectively associated with lower insulin resistance.

  • 30. Donat-Vargas, Carolina
    et al.
    Åkesson, Agneta
    Tornevi, Andreas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Wennberg, Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Sommar, Johan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Kiviranta, Hannu
    Rantakokko, Panu
    Bergdahl, Ingvar A.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Persistent Organochlorine Pollutants in Plasma, Blood Pressure, and Hypertension in a Longitudinal Study2018In: Hypertension, ISSN 0194-911X, E-ISSN 1524-4563, Vol. 71, no 6, p. 1258-1268Article in journal (Refereed)
    Abstract [en]

    Persistent organochlorine pollutants (POPs) have shown to be involved in the atherosclerotic process and to cause endothelial cell dysfunction. To assess longitudinally whether plasma concentrations of different POPs were associated with blood pressure and risk of hypertension in middle-aged women and men. Study subjects were 850 participants in the VIP (Västerbotten Intervention Programme) with 2 blood samples and blood pressure measurements, 10 years apart, during 1990 to 2003 (baseline) and during 2000 to 2013 (follow-up). Dioxin-like and nondioxin-like polychlorinated biphenyls (DL-PCBs, NDL-PCBs) and p,p'-dichlorodiphenyldichloroethylene (DDE) were measured. Associations were assessed using generalized estimating equations. At baseline sampling 49% and at follow-up 64% had hypertension. DL-PCBs and DDE, but not NDL-PCBs or hexachlorobenzene, were associated with hypertension. Only the association for DL-PCBs remained statistically significant after lipid-standardization and adjustment for body mass index and total serum lipids. The multivariable-adjusted odds ratio of hypertension based on repeated measurements were 1.52 (95% confidence interval, 1.08-2.13) for DL-PCBs (third versus first tertile of lipid-standardized POPs). In stratified adjusted analyses, odds ratio for those born after 1950 increased to 3.99 (95% confidence interval, 2.15-7.43), whereas no association was observed among those born earlier. Based on repeated measurements, the accumulated exposure to DL-PCBs and DDE, although less clear for the latter, may disrupt the normal blood pressure levels and increase the odds of hypertension. Moreover, individuals experiencing early-life POP exposure may be at elevated risk of vascular POP effects.

  • 31. Ek, Weronica E.
    et al.
    Tobi, Elmar W.
    Ahsan, Muhammad
    Lampa, Erik
    Ponzi, Erica
    Kyrtopoulos, Soterios A.
    Georgiadis, Panagiotis
    Lumey, L. H.
    Heijmans, Bastiaan T.
    Botsivali, Maria
    Bergdahl, Ingvar A.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Karlsson, Torgny
    Rask-Andersen, Mathias
    Palli, Domenico
    Ingelsson, Erik
    Hedman, Åsa K.
    Nilsson, Lena M.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Vineis, Paolo
    Lind, Lars
    Flanagan, James M.
    Johansson, Åsa
    Tea and coffee consumption in relation to DNA methylation in four European cohorts2017In: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 26, no 16, p. 3221-3231Article in journal (Refereed)
    Abstract [en]

    Lifestyle factors, such as food choices and exposure to chemicals, can alter DNA methylation and lead to changes in gene activity. Two such exposures with pharmacologically active components are coffee and tea consumption. Both coffee and tea has been suggested to play an important role in modulating disease-risk in humans by suppressing tumour progression, decreasing inflammation and influencing estrogen metabolism. These mechanisms may be mediated by changes in DNA methylation.To investigate if DNA methylation in blood is associated with coffee and tea consumption we performed a genome-wide DNA methylation study for coffee and tea consumption in four European cohorts (N = 3,096). DNA methylation was measured from whole blood at 421,695 CpG sites distributed throughout the genome and analysed in men and women both separately and together in each cohort. Meta-analyses of the results and additional regional-level analyses were performed.After adjusting for multiple testing, the meta-analysis revealed that two individual CpG-sites, mapping to DNAJC16 and TTC17, were differentially methylated in relation to tea consumption in women. No individual sites were associated in men or in the sex-combined analysis for tea or coffee. The regional analysis revealed that 28 regions were differentially methylated in relation to tea consumption in women. These regions contained genes known to interact with estradiol metabolism and cancer. No significant regions were found in the sex-combined and male-only analysis for either tea or coffee consumption.

  • 32. Engström, Karin S
    et al.
    Wennberg, Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine. Department of Medicine, Skellefteå Hospital, Skellefteå, Sweden.
    Strömberg, Ulf
    Bergdahl, Ingvar A.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lundh, Thomas
    Norberg, Margareta
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Rentschler, Gerda
    Vessby, Bengt
    Skerfving, Staffan
    Broberg, Karin
    Evaluation of the impact of genetic polymorphisms in glutathione-related genes on the association between methylmercury or n-3 polyunsaturated long chain fatty acids and risk of myocardial infarction: a case-control study2011In: Environmental health, ISSN 1476-069X, E-ISSN 1476-069X, Vol. 10, p. Article nr 33-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The n-3 polyunsaturated fatty acids eicosapentaenoic acid and docosahexaenoic acid, which are present in fish, are protective against myocardial infarction. However, fish also contains methylmercury, which influences the risk of myocardial infarction, possibly by generating oxidative stress. Methylmercury is metabolized by conjugation to glutathione, which facilitates elimination. Glutathione is also an antioxidant. Individuals with certain polymorphisms in glutathione-related genes may tolerate higher exposures to methylmercury, due to faster metabolism and elimination and/or better glutathione-associated antioxidative capacity. They would thus benefit more from the protective agents in fish, such as eicosapentaenoic+docosahexaenoic acid and selenium. The objective for this study was to elucidate whether genetic polymorphisms in glutathione-related genes modify the association between eicosapentaenoic+docosahexaenoic acid or methylmercury and risk of first ever myocardial infarction.

    METHODS: Polymorphisms in glutathione-synthesizing (glutamyl-cysteine ligase catalytic subunit, GCLC and glutamyl-cysteine ligase modifier subunit, GCLM) or glutathione-conjugating (glutathione S-transferase P, GSTP1) genes were genotyped in 1027 individuals from northern Sweden (458 cases of first-ever myocardial infarction and 569 matched controls). The impact of these polymorphisms on the association between erythrocyte-mercury (proxy for methylmercury) and risk of myocardial infarction, as well as between plasma eicosapentaenoic+docosahexaenoic acid and risk of myocardial infarction, was evaluated by conditional logistic regression. The effect of erythrocyte-selenium on risk of myocardial infarction was also taken into consideration.

    RESULTS: There were no strong genetic modifying effects on the association between plasma eicosapentaenoic+docosahexaenoic acid or erythrocyte-mercury and risk of myocardial infarction risk. When eicosapentaenoic+docosahexaenoic acid or erythrocyte-mercury were divided into tertiles, individuals with GCLM-588 TT genotype displayed a lower risk relative to the CC genotype in all but one tertile; in most tertiles the odds ratio was around 0.5 for TT. However, there were few TT carriers and the results were not statistically significant. The results were similar when taking plasma eicosapentaenoic+docosahexaenoic acid, erythrocyte-selenium and erythrocyte-mercury into account simultaneously.

    CONCLUSIONS: No statistically significant genetic modifying effects were seen for the association between plasma eicosapentaenoic+docosahexaenoic acid or erythrocyte-mercury and risk of myocardial infarction. Still, our results indicate that the relatively rare GCLM-588 TT genotype may have an impact, but a larger study is necessary for confirmation.

  • 33. Espín-Pérez, Almudena
    et al.
    Hebels, Dennie G. A. J.
    Kiviranta, Hannu
    Rantakokko, Panu
    Georgiadis, Panagiotis
    Botsivali, Maria
    Bergdahl, Ingvar
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Palli, Domenico
    Späth, Florentin
    Umeå University, Faculty of Medicine, Department of Biobank Research. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Biobank Research. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Chadeau-Hyam, Marc
    Kyrtopoulos, Soterios A
    Kleinjans, Jos C. S.
    de Kok, Theo M. C. M.
    Identification of Sex-Specific Transcriptome Responses to Polychlorinated Biphenyls (PCBs)2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 746Article in journal (Refereed)
    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.

  • 34. Freisling, Heinz
    et al.
    Moskal, Aurelie
    Ferrari, Pietro
    Nicolas, Genevieve
    Knaze, Viktoria
    Clavel-Chapelon, Francoise
    Boutron-Ruault, Marie-Christine
    Nailler, Laura
    Teucher, Birgit
    Grote, Verena A.
    Boeing, Heiner
    Clemens, Matthias
    Tjonneland, Anne
    Olsen, Anja
    Overvad, Kim
    Ramon Quiros, J.
    Duell, Eric J.
    Sanchez, Maria-Jose
    Amiano, Pilar
    Chirlaque, Maria-Dolores
    Barricarte, Aurelio
    Khaw, Kay-Tee
    Wareham, Nicholas J.
    Crowe, Francesca L.
    Gallo, Valentina
    Oikonomou, Eleni
    Naska, Androniki
    Trichopoulou, Antonia
    Palli, Domenico
    Agnoli, Claudia
    Tumino, Rosario
    Polidoro, Silvia
    Mattiello, Amalia
    Bueno-de-Mesquita, H. Bas
    Ocke, Marga C.
    Peeters, Petra H. M.
    Wirfalt, Elisabet
    Ericson, Ulrika
    Bergdahl, Ingvar A.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    Hjartaker, Anette
    Engeset, Dagrun
    Skeie, Guri
    Riboli, Elio
    Slimani, Nadia
    Dietary acrylamide intake of adults in the European Prospective Investigation into Cancer and Nutrition differs greatly according to geographical region2013In: European Journal of Nutrition, ISSN 1436-6207, E-ISSN 1436-6215, Vol. 52, no 4, p. 1369-1380Article in journal (Refereed)
    Abstract [en]

    Methodological differences in assessing dietary acrylamide (AA) often hamper comparisons of intake across populations. Our aim was to describe the mean dietary AA intake in 27 centers of 10 European countries according to selected lifestyle characteristics and its contributing food sources in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. In this cross-sectional analysis, 36 994 men and women, aged 35-74 years completed a single, standardized 24-hour dietary recall using EPIC-Soft. Food consumption data were matched to a harmonized AA database. Intake was computed by gender and center, and across categories of habitual alcohol consumption, smoking status, physical activity, education, and body mass index (BMI). Adjustment was made for participants' age, height, weight, and energy intake using linear regression models. Adjusted mean AA intake across centers ranged from 13 to 47 mu g/day in men and from 12 to 39 mu g/day in women; intakes were higher in northern European centers. In most centers, intake in women was significantly higher among alcohol drinkers compared with abstainers. There were no associations between AA intake and physical activity, BMI, or education. At least 50 % of AA intake across centers came from two food groups "bread, crisp bread, rusks" and "coffee." The third main contributing food group was "potatoes". Dietary AA intake differs greatly among European adults residing in different geographical regions. This observed heterogeneity in AA intake deserves consideration in the design and interpretation of population-based studies of dietary AA intake and health outcomes.

  • 35. Gasull, Magda
    et al.
    Pumarega, José
    Kiviranta, Hannu
    Rantakokko, Panu
    Raaschou-Nielsen, Ole
    Bergdahl, Ingvar A.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Sandanger, Torkjel Manning
    Goñi, Fernando
    Cirera, Lluís
    Donat-Vargas, Carolina
    Alguacil, Juan
    Iglesias, Mar
    Tjønneland, Anne
    Overvad, Kim
    Mancini, Francesca Romana
    Boutron-Ruault, Marie-Christine
    Severi, Gianluca
    Johnson, Theron
    Kühn, Tilman
    Trichopoulou, Antonia
    Karakatsani, Anna
    Peppa, Eleni
    Palli, Domenico
    Pala, Valeria
    Tumino, Rosario
    Naccarati, Alessio
    Panico, Salvatore
    Verschuren, Monique
    Vermeulen, Roel
    Rylander, Charlotta
    Haugdahl Nøst, Therese
    Rodríguez-Barranco, Miguel
    Molinuevo, Amaia
    Chirlaque, María-Dolores
    Ardanaz, Eva
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Key, Tim
    Ye, Weimin
    Umeå University, Faculty of Medicine, Department of Biobank Research. Department of Medical Epidemiology and Biostatistics Karolinska Institutet, Stockholm, Sweden.
    Jenab, Mazda
    Michaud, Dominique
    Matullo, Giuseppe
    Canzian, Federico
    Kaaks, Rudolf
    Nieters, Alexandra
    Nöthlings, Ute
    Jeurnink, Suzanne
    Chajes, Veronique
    Matejcic, Marco
    Gunter, Marc
    Aune, Dagfinn
    Riboli, Elio
    Agudo, Antoni
    Gonzalez, Carlos Alberto
    Weiderpass, Elisabete
    Bueno-de-Mesquita, Bas
    Duell, Eric J.
    Vineis, Paolo
    Porta, Miquel
    Methodological issues in a prospective study on plasma concentrations of persistent organic pollutants and pancreatic cancer risk within the EPIC cohort2019In: Environmental Research, ISSN 0013-9351, E-ISSN 1096-0953, Vol. 169, p. 417-433Article in journal (Refereed)
    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.

  • 36. Gaudet, Mia M
    et al.
    Deubler, Emily L
    Kelly, Rachel S
    Diver, W Ryan
    Teras, Lauren R
    Hodge, James M
    Levine, Keith E
    Haines, Laura G
    Lundh, Thomas
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Palli, Domenico
    Vineis, Paolo
    Bergdahl, Ingvar
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Gapstur, Susan M
    Kyrtopoulos, Soterios A
    Blood Levels of Cadmium and Lead in Relation to Breast Cancer Risk in Three Prospective Cohorts.2019In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 144, no 5, p. 1010-1016Article in journal (Refereed)
    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. 

  • 37. Georgiadis, Panagiotis
    et al.
    Gavriil, Marios
    Rantakokko, Panu
    Ladoukakis, Efthymios
    Botsivali, Maria
    Kelly, Rachel S
    Bergdahl, Ingvar
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Kiviranta, Hannu
    Vermeulen, Roel C H
    Späth, Florentin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hebbels, Dennie G A J
    Kleinjans, Jos C S
    de Kok, Theo M C M
    Palli, Domenico
    Vineis, Paolo
    Kyrtopoulos, Soterios A
    DNA methylation profiling implicates exposure to PCBs in the pathogenesis of B-cell chronic lymphocytic leukemia2019In: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 126, p. 24-36Article in journal (Refereed)
    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.

  • 38. Georgiadis, Panagiotis
    et al.
    Hebels, Dennie G
    Valavanis, Ioannis
    Liampa, Irene
    Bergdahl, Ingvar A
    Umeå University, Faculty of Medicine, Department of Biobank Research. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Palli, Domenico
    Chadeau-Hyam, Marc
    Chatziioannou, Aristotelis
    Jennen, Danyel G J
    Krauskopf, Julian
    Jetten, Marlon J
    Kleinjans, Jos C S
    Vineis, Paolo
    Kyrtopoulos, Soterios A
    Omics for prediction of environmental health effects: Blood leukocyte-based cross-omic profiling reliably predicts diseases associated with tobacco smoking.2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 20544Article in journal (Refereed)
    Abstract [en]

    The utility of blood-based omic profiles for linking environmental exposures to their potential health effects was evaluated in 649 individuals, drawn from the general population, in relation to tobacco smoking, an exposure with well-characterised health effects. Using disease connectivity analysis, we found that the combination of smoking-modified, genome-wide gene (including miRNA) expression and DNA methylation profiles predicts with remarkable reliability most diseases and conditions independently known to be causally associated with smoking (indicative estimates of sensitivity and positive predictive value 94% and 84%, respectively). Bioinformatics analysis reveals the importance of a small number of smoking-modified, master-regulatory genes and suggest a central role for altered ubiquitination. The smoking-induced gene expression profiles overlap significantly with profiles present in blood cells of patients with lung cancer or coronary heart disease, diseases strongly associated with tobacco smoking. These results provide proof-of-principle support to the suggestion that omic profiling in peripheral blood has the potential of identifying early, disease-related perturbations caused by toxic exposures and may be a useful tool in hazard and risk assessment.

  • 39. Georgiadis, Panagiotis
    et al.
    Liampa, Irene
    Hebels, Dennie G
    Krauskopf, Julian
    Chatziioannou, Aristotelis
    Valavanis, Ioannis
    de Kok, Theo M C M
    Kleinjans, Jos C S
    Bergdahl, Ingvar A
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Melin, Beatrice
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Spaeth, Florentin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Palli, Domenico
    Vermeulen, R C H
    Vlaanderen, J
    Chadeau-Hyam, Marc
    Vineis, Paolo
    Kyrtopoulos, Soterios A
    Evolving DNA methylation and gene expression markers of B-cell chronic lymphocytic leukemia are present in pre-diagnostic blood samples more than 10 years prior to diagnosis2017In: BMC Genomics, ISSN 1471-2164, E-ISSN 1471-2164, Vol. 18, article id 728Article in journal (Refereed)