Anneli Sundkvist

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.

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 Västerbotten 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.

OBJECTIVES: 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. MATERIALS AND METHODS: 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. RESULTS: Between the European cities, the B-Pb and B-Cd results vary little (range of geometric means: 13.5-27.0 μg/l and 0.25-0.65 μg/l, respectively); the variation of B-Hg was larger (0.40-1.38 μg/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 μg/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. CONCLUSIONS: 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.

Abstract 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. Cancer Epidemiol Biomarkers Prev; 27(5); 531–40. ©2018 AACR.