APH 2004, 62, 39-48:
Simplicity and complexity of genetic susceptibility in the occupational environment.
I. Decordier, P. Aka, N. Lombaert, A. Vanhauwaert, R. Mateuca, M. Kirsch-Volders
Keywords: Occupational exposure, genotype, phenotype, genetic susceptibility
The individual response to physical or chemical stress may vary as a function of the particular gene combination regarding metabolism of chemical mutagens, DNA repair, cell death and cell cycle control. Nowadays, methods for genotyping have become easy to perform and in vitro phe-notyping approaches are in development. It is therefore interesting to consider whether these methods assessing genetic susceptibility can be implemented for occupational biomonitoring. A major question is whether genotyping or phenotyping or both has the best predictive value for can-cer risk and should be applied. To fully understand the relationship between genotype and phenotype, knowledge about the different factors influencing the expression of a genotype into a phenotype is still missing.In this review we compare advantages and disadvantages of genotyping and phenotyping to assess individual susceptibility and discuss the different parameters modifying the genotype-phenotype relationship. The importance of both approaches is illustrated by a study conducted in our laboratory in workers exposed to low dose ionising radiation. Genotyping forhOGGI, XRCC1 and XRCC3, enzymes involved in base excision and double strand DNA repair was performed; the DNA strand break repair phenotype was assessed by in vitro challenging with y-rays. The results indicate that hOGG 1 and XRCC3 may be predictive for induced mutations after exposure to ionising radiation, and that the in vitro repair phenotype assay might also be a valuable approach to assess individual susceptibility. Additional studies on larger population samples are needed before advising these genetic tests for susceptibility in daily practice.