Multiplex Genotyping as a Biomarker for Susceptibility to Carcinogenic Exposure in the FLEHS Biomonitoring Study

Abstract

Cancer has been suggested to result from interactions between genetic and environmental factors, and certain subgroups in the general population may be at increased risk because of their relatively higher susceptibility to environmental carcinogens. The current study, part of a large biomonitoring study conducted in Flanders from 2002 to 2006 (The Flanders Environment and Health Survey), aims to determine these susceptible subpopulations based on multiple genotypic differences between individuals. A random selection of 429 adolescents and 361 adults was genotyped for 36 polymorphisms in 23 genes selected because of their known role in carcinogen metabolism, DNA repair, and oxidative stress. In both age groups, relationships between endogenous exposure to organochloride substances (polychlorinated biphenyl, hexachlorobenzene, dichlorodiphenyl dichloroethane), metals (cadmium, lead), and urinary metabolites (1-hydroxypyrene, trans-trans muconic acid) versus genotoxic effects (Comet assay and micronuclei in lymphocytes, and urinary 8-hydroxydeoxyguanosine) were investigated. In addition, in the study among adults, the relationship of these exposures with several tumor markers (prostate-specific antigen, carcinoembryonic antigen, and p53) was tested. The impact of the genotype on established exposure-effect relationships was evaluated. Eight exposure-effect relationships were found, including three novel associations, with an impact of various genotypes, predominantly affecting biotransformation and oxidative stress response. This study shows that at least part of the interindividual differences in relationships between carcinogen exposure and genotoxic effect can be explained by genotypic differences, enabling the identification of more susceptible subgroups for environmental cancer risks. This may be of relevance for environmental health policy setting. (Cancer Epidemiol Biomarkers Prev 2008;17(8):1902 -12)

Genetic Variants of Nucleotide Excision Repair Genes Are Associated with DNA Damage in Coke Oven Workers

“…The reason may be due to differences in exogenous PAH exposure levels and individual genetic background, possibly through gene-environment and gene-gene interactions (17). In the present study, we hypothesized that the common variants in the NER genes may influence the DNA damage levels of coke oven workers who had been exposed to different concentrations of PAHs in their workplaces.…”

Cytogenetic biomonitoring of inhabitants of a large uranium mineralization area: the municipalities of Monte Alegre, Prainha, and Alenquer, in the State of Pará, Brazil

“…However, for the study of another kind of association, such as the identification of interindividual differences in environmental cancer risk assessment (Ketelslegers et al 2008), the sample size of this present study may be considered small.…”

Distinct genotype-dependent differences in transcriptome responses in humans exposed to environmental carcinogens

“…Within FLEHS, these have previously been demonstrated to be correlated with data on internal exposures to organochloride substances, metals and urinary metabolites (3). In order to investigate whether gene expression is associated with these biomarkers, we fitted a mixed model including these biomarkers as the variable of interest.…”

“…The Flemish Environment and Health Survey (FLEHS), which was initiated in 2002 and measures exposure to known and suspected environmental carcinogens, aims to establish relationships between these exposures and biomarkers of adverse health effects in order to obtain a better understanding of the relation between health risks and exposures (3). Conventional approaches in cancer risk assessment assume that all subjects have the same susceptibility towards a specific dose of a compound, and furthermore, do not take into account that people under daily life circumstances are exposed to a mixture of environmental carcinogens, rather than to a single compound.…”