Lymphoma; Pre-diagnostic Blood Markers and Occupational and Environmental Exposures.

2.50
Hdl Handle:
http://hdl.handle.net/10146/234473
Title:
Lymphoma; Pre-diagnostic Blood Markers and Occupational and Environmental Exposures.
Authors:
Saberi Hosnijeh, Fatemeh
Other Titles:
Lymfomen; pre-diagnostische markers in bloed en beroepsmatige en milieugerelateerde blootstellingen. (in Netherlands)
Abstract:
The overall aim of this thesis is to study the possible perturbations of the immune system by occupational and environmental risk factors of Non-Hodgkin lymphoma (NHL) and to study these changes in relation to NHL risk in prospective cohorts. In the first section, we validated the application of single blood cytokine measurements as a biomarker of immune status in prospective epidemiological studies. Potential utility of stored blood samples of a prospective cohort was evaluated by the effect of different blood sample types and freeze-thaw cycles on cytokine levels. This study showed strong correlations between different sample types. Moreover, freeze-thaw cycles did not markedly change cytokine levels. The intra-individual variance in cytokine levels was much smaller than the inter-individual variance which supports the notion that a single cytokine measurement can be used to characterize an individual's immune profile prospectively. Subsequently, we assessed the levels of these cytokines in pre-diagnostic blood samples of participants of a case–control study nested into the Italian European Prospective Investigation into Cancer and Nutrition cohort (EPIC) and determined their association with the risk of developing NHL. The results suggest a possible association between increased/decreased plasma levels of interleukin (IL)2, inter-cellular adhesion molecule, interferon gamma (IFN-γ), and tumor necrosis factor alpha with NHL risk. In the second section, we studied the possible immunological effects of two possibly lymphomagens: an occupational exposure (i.e. 2,3,7,8- tetrachlorodibenzo-p-dioxin (TCDD)) and an environmental risk factor (i.e. obesity). We assessed a broad range of immunologic parameters directed towards detecting abnormalities in the humoral and cellular arms of the immune system among workers exposed to chlorophenoxy herbicides, chlorophenols and dioxins in particular TCDD. These studies showed that plasma TCDD levels were not associated with markers of humoral immunity with the possible exception of a decrease in complement factor 4 levels. Most lymphocyte subsets, in particular the B cell compartment, showed a decrease in cell counts with increasing levels of TCDD. Moreover, blood levels of most cytokines, chemokines and growth factors had a negative association with TCDD levels with a formal statistical significance for fractalkine, transforming growth factor alpha and fibroblast growth factor 2. These changes were independent from the changes in blood cell counts. Our findings support the notion that dioxin exposure can have an adverse impact on the immune system and likely suppresses the immune system. To identify immunologic hallmarks of obesity, we measured plasma levels of cytokines in pre-diagnostic blood samples of participants of a case-control study nested in the Italian EPIC cohort. IL8, IL10, IFN-γ, and interferon-induced protein 10 (IP10) were related to obesity. However, the set of obesity predictors (IL8, IL10, IFN-γ, IP10) were not associated with future NHL risk. Our studies support that subtle perturbations in the immune system may precede lymphoma development and suggest that B cell activation, chronic inflammation and/or an unbalance in Th1/Th2-responses are likely important phenomena in lymphomagenesis. Although, possible occupational and environmental risk factors of NHL influence the immune system they did not pertubate immune markers shown to be associated with future NHL risk.
Citation:
Saberi Hosnijeh, F.: Lymphoma; pre-diagnostic blood markers and occupational and environmental exposures . Thesis Utrecht University 2012.
Publisher:
Utrecht University, 2012
Issue Date:
2012
URI:
http://hdl.handle.net/10146/234473
Additional Links:
http://igitur-archive.library.uu.nl/dissertations/2012-0320-200539/UUindex.html
Type:
Thesis
Language:
en
ISBN:
978-90-393-5749-1
Sponsors:
Some studies described in this thesis were financially supported by ECNIS (European Cancer Risk, Nutrition and Individual Susceptibility), a network of excellence operating within the European Union 6th Framework Program, Priority 5: "Food Quality and Safety" (Contract No 513943).
Appears in Collections:
Theses

Full metadata record

DC FieldValue Language
dc.contributor.authorSaberi Hosnijeh, Fatemehen_GB
dc.date.accessioned2012-07-19T08:57:27Z-
dc.date.available2012-07-19T08:57:27Z-
dc.date.issued2012-
dc.identifier.citationSaberi Hosnijeh, F.: Lymphoma; pre-diagnostic blood markers and occupational and environmental exposures . Thesis Utrecht University 2012.en_GB
dc.identifier.isbn978-90-393-5749-1-
dc.identifier.urihttp://hdl.handle.net/10146/234473-
dc.description.abstractThe overall aim of this thesis is to study the possible perturbations of the immune system by occupational and environmental risk factors of Non-Hodgkin lymphoma (NHL) and to study these changes in relation to NHL risk in prospective cohorts. In the first section, we validated the application of single blood cytokine measurements as a biomarker of immune status in prospective epidemiological studies. Potential utility of stored blood samples of a prospective cohort was evaluated by the effect of different blood sample types and freeze-thaw cycles on cytokine levels. This study showed strong correlations between different sample types. Moreover, freeze-thaw cycles did not markedly change cytokine levels. The intra-individual variance in cytokine levels was much smaller than the inter-individual variance which supports the notion that a single cytokine measurement can be used to characterize an individual's immune profile prospectively. Subsequently, we assessed the levels of these cytokines in pre-diagnostic blood samples of participants of a case–control study nested into the Italian European Prospective Investigation into Cancer and Nutrition cohort (EPIC) and determined their association with the risk of developing NHL. The results suggest a possible association between increased/decreased plasma levels of interleukin (IL)2, inter-cellular adhesion molecule, interferon gamma (IFN-γ), and tumor necrosis factor alpha with NHL risk. In the second section, we studied the possible immunological effects of two possibly lymphomagens: an occupational exposure (i.e. 2,3,7,8- tetrachlorodibenzo-p-dioxin (TCDD)) and an environmental risk factor (i.e. obesity). We assessed a broad range of immunologic parameters directed towards detecting abnormalities in the humoral and cellular arms of the immune system among workers exposed to chlorophenoxy herbicides, chlorophenols and dioxins in particular TCDD. These studies showed that plasma TCDD levels were not associated with markers of humoral immunity with the possible exception of a decrease in complement factor 4 levels. Most lymphocyte subsets, in particular the B cell compartment, showed a decrease in cell counts with increasing levels of TCDD. Moreover, blood levels of most cytokines, chemokines and growth factors had a negative association with TCDD levels with a formal statistical significance for fractalkine, transforming growth factor alpha and fibroblast growth factor 2. These changes were independent from the changes in blood cell counts. Our findings support the notion that dioxin exposure can have an adverse impact on the immune system and likely suppresses the immune system. To identify immunologic hallmarks of obesity, we measured plasma levels of cytokines in pre-diagnostic blood samples of participants of a case-control study nested in the Italian EPIC cohort. IL8, IL10, IFN-γ, and interferon-induced protein 10 (IP10) were related to obesity. However, the set of obesity predictors (IL8, IL10, IFN-γ, IP10) were not associated with future NHL risk. Our studies support that subtle perturbations in the immune system may precede lymphoma development and suggest that B cell activation, chronic inflammation and/or an unbalance in Th1/Th2-responses are likely important phenomena in lymphomagenesis. Although, possible occupational and environmental risk factors of NHL influence the immune system they did not pertubate immune markers shown to be associated with future NHL risk.en_GB
dc.description.sponsorshipSome studies described in this thesis were financially supported by ECNIS (European Cancer Risk, Nutrition and Individual Susceptibility), a network of excellence operating within the European Union 6th Framework Program, Priority 5: "Food Quality and Safety" (Contract No 513943).en_GB
dc.language.isoenen
dc.publisherUtrecht University, 2012en_GB
dc.relation.urlhttp://igitur-archive.library.uu.nl/dissertations/2012-0320-200539/UUindex.htmlen_GB
dc.subjectNon-Hodgkin lymphomaen_GB
dc.subjectOccupational Exposureen_GB
dc.subjectEnvironmental exposureen_GB
dc.subjectDioxinsen_GB
dc.subjectRisk factorsen_GB
dc.subjectBiological markersen_GB
dc.subjectImmune systemen_GB
dc.subjectLymphocytesen_GB
dc.subjectCytokinesen_GB
dc.subjectObesityen_GB
dc.titleLymphoma; Pre-diagnostic Blood Markers and Occupational and Environmental Exposures.en
dc.title.alternativeLymfomen; pre-diagnostische markers in bloed en beroepsmatige en milieugerelateerde blootstellingen. (in Netherlands)en_GB
dc.typeThesisen
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