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Danitsja M. van Leeuwen,¹ Ralph W.H. Gottschalk,¹ Greet Schoeters,² Nicolas A. van Larebeke,³ Vera Nelen,⁴ Willy F. Baeyens,⁵ Jos C.S. Kleinjans,¹ and Joost H.M. van Delft¹

¹Department of Health Risk Analysis and Toxicology, Maastricht University, Maastricht, the Netherlands, ²Center of Expertise in Environmental Toxicology, Flemish Institute for Technological Research, Mol, Belgium; ³Study Centre for Carcinogenesis and Primary Prevention of Cancer, Ghent University Hospital, Ghent, Belgium, ⁴Provincial Institute of Hygiene, Antwerp, Belgium; ⁵Laboratory of Analytical and Environmental Chemistry, Vrije Universiteit Brussel, Brussels, Belgium

Abstract
Background: Human carcinogenesis is known to be initiated and/or promoted by exposure to chemicals that occur in the environment. Molecular cancer epidemiology is used to identify human environmental cancer risks by applying a range of effect biomarkers, which tend to be nonspecific and do not generate insights into underlying modes of action. Toxicogenomic technologies may improve on this by providing the opportunity to identify molecular biomarkers consisting of altered gene expression profiles.

Objectives: The aim of the present study was to monitor the expression of selected genes in a random sample of adults in Flanders selected from specific regions with (presumably) different environmental burdens. Furthermore, associations of gene expression with blood and urinary measures of biomarkers of exposure, early phenotypic effects, and tumor markers were investigated.

Results: Individual gene expression of cytochrome p450 1B1, activating transcription factor 4, mitogen-activated protein kinase 14, superoxide dismutase 2 (Mn) , chemokine (C-X-C motif) ligand 1 (melanoma growth stimulating activity, alpha) , diacylglycerol O-acyltransferase homolog 2 (mouse) , tigger transposable element derived 3, andPTEN-induced putative kinase1 were measured by means of quantitative polymerase chain reaction in peripheral blood cells of 398 individuals. After correction for the confounding effect of tobacco smoking, inhabitants of the Olen region showed the highest differences in gene expression levels compared with inhabitants from the Gent and fruit cultivation regions. Importantly, we observed multiple significant correlations of particular gene expressions with blood and urinary measures of various environmental carcinogens.

Conclusions: Considering the observed significant differences between gene expression levels in inhabitants of various regions in Flanders and the associations of gene expression with blood or urinary measures of environmental carcinogens, we conclude that gene expression profiling appears promising as a tool for biological monitoring in relation to environmental exposures in humans.

Key words: biomarker, biomonitoring, environmental carcinogens, human blood, transcriptomics. Environ Health Perspect 116:1519–1525 (2008) .  doi:10.1289/ehp.11401 available via http://dx.doi.org/ [Online 23 June 2008]

Address correspondence to D.M. van Leeuwen, Department of Health Risk Analysis and Toxicology, Maastricht University, P.O. Box 616, 6200 MD Maastricht, the Netherlands. Telephone: 31 (0) 433882127. Fax: 31 (0) 433884146. E-mail: d.vanleeuwen@grat.unimaas.nl

We thank the volunteers for participating and the nurses for the sample collections.

This study was conducted as part of the Flemish Centre of Expertise of Environment and Health and was commissioned, financed, and steered by the Ministry of the Flemish Community (Department of Economics, Science and Innovation ; Flemish Agency for Care and Health ; and Department of Environment, Nature and Energy) . The sponsor was not involved in analysis or interpretation of the data.

The authors declare they have no competing financial interests.

Received 21 February 2008 ; accepted 23 June 2008.