This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Ketelslegers, H. B. Articles by Kleinjans, J. C.S. Search for Related Content PubMed PubMed Citation Articles by Ketelslegers, H. B. Articles by Kleinjans, J. C.S.

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

¹ Department of Health Risk Analysis and Toxicology, Maastricht University, Maastricht, The Netherlands; ² Flemish Institute for Technological Research, Mol, Belgium; ³ Analytical and Environmental Chemistry Department, ANCH, Vrije Universiteit Brussel, Brussels, Belgium; and ⁴ Department of Radiotherapy, Nuclear Medicine and Experimental Cancerology, Ghent University, Ghent, Belgium

Requests for reprints: Hans B. Ketelslegers, Department of Health Risk Analysis and Toxicology, Maastricht University, P.O. Box 616, 6200 MD, Maastricht, The Netherlands. Phone: 31-43-3881218; Fax: 31-43-3884146. E-mail: H.Ketelslegers{at}grat.unimaas.nl.

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)