Prediagnostic plasma concentrations of organochlorines and risk of B-cell non-Hodgkin lymphoma in envirogenomarkers: a nested case-control study

Background: Evidence suggests a largely environmental component to non-Hodgkin’s lymphoma (NHL). Persistent organic pollutants (POPs) including polychlorinated biphenyls (PCBs), DDE and HCB have been repeatedly implicated, but the literature is inconsistent and a causal relationship remains to be determined. Methods: The EnviroGenoMarkers study is nested within two prospective cohorts EPIC-Italy and the Northern Sweden Health and Disease Study. Six PCB congeners, DDE and HCB were measured in blood plasma samples provided at recruitment using gas-chromatography mass spectrometry. During 16 years follow-up 270 incident cases of B-cell NHL (including 76 cases of multiple myeloma) were diagnosed. Cases were matched to 270 healthy controls by centre, age, gender and date of blood collection. Cases were categorised into ordered quartiles of exposure for each POP based on the distribution of exposure in the control population. Logistic regression was applied to assess the association with risk, multivariate and stratified analyses were performed to identify confounders or effect modifiers. Results: The exposures displayed a strong degree of correlation, particularly amongst those PCBs with similar degrees of chlorination. There was no significant difference (p 90th percentile) the association was null for all POPs Conclusion: We report no evidence that a higher body burden of PCBs, DDE or HCB increased the risk of subsequent NHL diagnosis. Significantly inverse associations were noted for males with a number of the investigated POPs. We hypothesize these unexpected relationships may relate to the subtype composition of our population, effect modification by BMI or other unmeasured confounding. This study provides no additional support for the previously observed role of PCBs, DDE and HCB as risk factors for NHL

Exploring the cellular network of metabolic flexibility in the adipose tissue

Abstract Background Metabolic flexibility is the ability of cells to change substrates for energy production based on the nutrient availability and energy requirement. It has been shown that metabolic flexibility is impaired in obesity and chronic diseases such as type 2 diabetes mellitus, cardiovascular diseases, and metabolic syndrome, although, whether it is a cause or an effect of these conditions remains to be elucidated. Main body In this paper, we have reviewed the literature on metabolic flexibility and curated pathways and processes resulting in a network resource to investigate the interplay between these processes in the subcutaneous adipose tissue. The adipose tissue has been shown to be responsible, not only for energy storage but also for maintaining energy homeostasis through oxidation of glucose and fatty acids. We highlight the role of pyruvate dehydrogenase complex–pyruvate dehydrogenase kinase (PDC-PDK) interaction as a regulatory switch which is primarily responsible for changing substrates in energy metabolism from glucose to fatty acids and back. Baseline gene expression of the subcutaneous adipose tissue, along with a publicly available obesity data set, are visualised on the cellular network of metabolic flexibility to highlight the genes that are expressed and which are differentially affected in obesity. Conclusion We have constructed an abstracted network covering glucose and fatty acid oxidation, as well as the PDC-PDK regulatory switch. In addition, we have shown how the network can be used for data visualisation and as a resource for follow-up studies