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.