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Role of environmental pollutants in human disease

Environmental pollution can play a vital role in chronic diseases such as cancer as well as many neurological and immune diseases. European funding is helping to develop a new generation of biomarkers to study the effect of environmental agents in human disease.

The EU-funded 'Genomics biomarkers of environmental health' ENVIROGENOMARKERS project involved the first large-scale application of global analysis ('omics') technologies on biosamples from existing, population-based and disease-oriented cohorts with the aim to identify novel biomarkers of disease risk and environmental exposure.

Biosamples including blood, urine, and cord blood from three cohorts — northern Sweden health and disease study, EPIC-Italy and the Rhea mother-child study — were used. These samples had been collected years ago from people who were at the time healthy (or during pregnancy and at birth, in the case of the latter study) and whose health status was subsequently followed up. Additionally, information on diet, lifestyle, air pollution exposure and other environmental factors was also incorporated into the study.

The ENVIROGENOMARKERS scientists analysed the above samples using microarray-based technology for whole-genome expression and epigenetic profiling, ultraprecision liquid chromatography with mass spectrometry (UPLC-MS/MS) for metabolomic profiling and multiplex ELISA for wide-target proteomics, along with advanced bioinformatics and systems biology tools.

In addition, they measured in the same biosamples the levels of persistent organic pollutants (such as polychlorinated biphenyls (PCBs), hexachlorobenzene (HCB) and polybrominated diphenyl ether), cadmium and phthalates.

The omics data obtained were evaluated statistically to look for biomarkers of disease risk, i.e. for signals which differed between persons who subsequently developed disease from those who remained healthy. The data was also assessed for biomarkers of exposure, i.e. for signals that correlate with measured levels of the environmental chemicals mentioned above.

This evaluation revealed a large number of transcriptomic and epigenetic signals- and a small number of proteomic signals, which were associated with the risk of a future appearance of lymphoma, particularly B-cell chronic lymphatic leukaemia (BCLL). Significant numbers of signals associating with exposure to PCBs and HCB were also found, some of which fall on cancer-related pathways, whose significance in relation to lymphoma causation requires further investigation.

The analyses of samples from pregnant mothers or newborns showed statistically significant associations between certain metabolite levels and neurodevelopment. Furthermore, evaluation of the metabolomics profiles obtained with sera of pregnant mothers revealed signals predictive of pre-term birth, gestational age and foetal weight growth restriction, as well as signals reflecting maternal smoking (passive or active) during pregnancy.

Results were disseminated widely via the project website, lectures, conferences, workshops, newsletters and several scientific peer-reviewed publications. The ENVIROGENOMARKERS project outcomes have paved the way for the discovery of novel biomarkers linking environmental exposure and disease using biosamples from already existing biobanks that have been in storage for decades.

Related link:
http://cordis.europa.eu/

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