In the determination of cancer risk, genetic susceptibility has been associated with interindividual variations in the capacity t o metabolise occupational and environmental agents. Sequence variations in genes coding for metabolising enzymes are considered a plausible mechanism which may explain this va-riation. Rapid technological progress in human genome research has fired enthusiasm for investigating polymorphic genes in studies of complex diseases.To date, however, the majority of such studies have failed to provide convincing results. Methodological shortco-mings in the conduct of many studies have resulted in inconsistent results, mainly caused by insufficient statistical power. But also meta-analyses and pooled analyses of studies have not lent sup-port to the (rather naive) hypothesis that a single genetic variant could be a significant genetic risk factor for common diseases, in view of the immense number of sequence variants and complex network of genes. Therefore, screening for genetic variants in routine clinical investigations in occupational and environmental medicine cannot be recommended. In addition to ethical and legal issues, screening for genetic variants is not in accordance with the scientific guidelines for disease markers. On the other hand, i t is plausible that certain combinations of genetic variants may contribute to the wide range of responses observed among workers exposed to hazardous agents.Therefore, research in this field is needed with meaningful studies conducted in accordance with the guidelines for Good Epidemiological Practice and Good Laboratory Practice (GEP, GLP).
