Immune marker changes and risk of multiple myeloma: a nested case-control study using repeated prediagnostic blood samples

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

Pesticide Exposure of Residents Living Close to Agricultural Fields in the Netherlands: Protocol for an Observational Study

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Spatio-temporal variation of outdoor and indoor pesticide air concentrations in homes near agricultural fields

Background: Previous research has shown that many current-use pesticides can be detected in air around application areas. Environmental exposure to pesticides may cause adverse health effects, necessitating accurate assessment of outdoor and indoor air concentrations for people living close to spraying sites. We evaluated outdoor and indoor air concentrations of different pesticides, as well as factors influencing spatial and temporal variations. Methods: We collected outdoor air samples at 58 homes located within 250 m of bulb fields and 15 control homes located further than 500 m from any agricultural field. Outdoor air sampling following a pesticide spray event was performed 24-h a day for 7 consecutive days. Two full day samples were collected at the same locations during a non-use period. In homes located within 50 m from agricultural fields (N = 18), indoor air was also sampled for the first 24 h after field spraying. Samples were analysed for a total of 46 pesticides and degradation products. From these, 11 were actively used on nearby fields, 3 were used in bulb disinfection and 6 were degradation products. Results: Compared to non-use periods, pesticides concentrations were 5–10 times higher in outdoor air during application periods. Similar concentration differences were observed between exposed homes and controls both during pesticide use and non-use period. For 14 pesticides, there were moderate correlations (spearman > 0.4–0.7) between outdoor and indoor air concentrations. Wind direction, evapotranspiration and agricultural area surrounding a home were the most important determinants of air concentration of the applied pesticides. Conclusions: This study provides strong evidence suggesting that environmental exposure to pesticides via air is not limited to the day of application and may occur year-round. The concentrations appeared higher during the use period. Factors influencing the local fate of pesticides in air may differ significantly between compounds

Spatio-temporal variation of outdoor and indoor pesticide air concentrations in homes near agricultural fields

Background: Previous research has shown that many current-use pesticides can be detected in air around application areas. Environmental exposure to pesticides may cause adverse health effects, necessitating accurate assessment of outdoor and indoor air concentrations for people living close to spraying sites. We evaluated outdoor and indoor air concentrations of different pesticides, as well as factors influencing spatial and temporal variations. Methods: We collected outdoor air samples at 58 homes located within 250 m of bulb fields and 15 control homes located further than 500 m from any agricultural field. Outdoor air sampling following a pesticide spray event was performed 24-h a day for 7 consecutive days. Two full day samples were collected at the same locations during a non-use period. In homes located within 50 m from agricultural fields (N = 18), indoor air was also sampled for the first 24 h after field spraying. Samples were analysed for a total of 46 pesticides and degradation products. From these, 11 were actively used on nearby fields, 3 were used in bulb disinfection and 6 were degradation products. Results: Compared to non-use periods, pesticides concentrations were 5–10 times higher in outdoor air during application periods. Similar concentration differences were observed between exposed homes and controls both during pesticide use and non-use period. For 14 pesticides, there were moderate correlations (spearman > 0.4–0.7) between outdoor and indoor air concentrations. Wind direction, evapotranspiration and agricultural area surrounding a home were the most important determinants of air concentration of the applied pesticides. Conclusions: This study provides strong evidence suggesting that environmental exposure to pesticides via air is not limited to the day of application and may occur year-round. The concentrations appeared higher during the use period. Factors influencing the local fate of pesticides in air may differ significantly between compounds

Immune marker changes and risk of multiple myeloma: a nested case-control study using repeated prediagnostic blood samples

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

Plasma cytokines and future risk of non-Hodgkin lymphoma (NHL): a case-control study nested in the Italian European Prospective Investigation into Cancer and Nutrition.

BACKGROUND: Recently, biological markers related to the immune system such as cytokines have been studied to further understand the etiology of non-Hodgkin Lymphoma (NHL). However, to date, there are no studies that have studied cytokine levels prospectively in relation to NHL risk in the general population. METHODS: Using bead-based immunoassays, plasma levels of 11 cytokines, 4 chemokines, and 1 adhesion molecules were measured in prediagnostic blood samples of 86 NHL cases and 86 matched controls (average time between blood collection and diagnosis, 4.5 y). Conditional logistic regression adjusted for body mass index and alcohol consumption was used to analyze the association between individual plasma cytokine levels and the risk of developing NHL. RESULTS: In multivariate models, excluding cases diagnosed within 2 years after inclusion, we observed a significant association for interleukin 2 (IL2; P trend = 0.004), interferon (IFN)-gamma (P trend = 0.05), and intercellular adhesion molecule (ICAM) (P trend = 0.04). Subanalyses of B-cell NHL patients showed a significant association with IL2 (P trend = 0.003), tumor necrosis factor-alpha (TNF-alpha; P trend = 0.03), and ICAM (P trend = 0.04) and a borderline association with IL5 (P trend = 0.07) and IFN-gamma (P trend = 0.08). CONCLUSIONS: The results of this study suggest, in a prospective setting, a possible association between plasma levels of IL2, ICAM, IFN-gamma, and TNF-alpha with NHL risk and provide some evidence that risk of NHL might be related to a downregulation of T helper 1 cytokines. IMPACT: Identification of subtle changes in immune response regulation quantified by plasma cytokine levels possibly provides new insights in the etiology of NHL