Differences in biological responses to exposure to hazardous airborne substances between children and adults have been reported, suggesting children to be more susceptible. Aim of this study was to improve our understanding of differences in susceptibility in cancer risk associated with air pollution by comparing genome-wide gene expression profiles in peripheral blood of children and their parents. Gene expression analysis was performed in blood from children and parents living in two different regions in the Czech Republic, with different levels of air pollution. Data were analyzed by two different approaches; one method first selected significantly differentially expressed genes and analyzed these gene lists for overrepresented biological processes, while the other applied the T-profiler tool to directly perform pathway analyses on the total gene set without pre-selection of significantly modulated gene expressions. In addition, gene expressions in both children and adults were investigated for associations with micronuclei frequencies. Both analysis approaches returned considerably more genes or gene groups and pathways that significantly differed between children from both regions than between parents. Very little overlap was observed between children and adults. The two most important biological processes or molecular functions significantly modulated in children, but not in adults, are nucleosome and immune response related. Our study suggests differences between children and adults in relation to air pollution exposure at the transcriptome level. The findings underline the necessity of implementing environmental health policy measures specifically for protecting children's health. AD - Department of Health Risk Analysis and Toxicology, Maastricht University, Maastricht, the Netherlands.