SCIENTIFIC AND ETHICAL ASPECTS OF GENETIC SCREENING OF WORKERS FOR CANCER RISK - THE CASE OF THE N-ACETYLTRANSFERASE PHENOTYPE

Our expanding capacity to detect human genetic susceptibility to vario us chronic diseases presents us with the opportunity to screen asympto matic people for purposes of employment, insurance or credit. It also brings with it the responsibility of deciding the ethical and social v alue of such applications. This paper addresses scientific and ethical issues involved in the use of genetic screening techniques which inte nd to identify individuals that have more than average susceptibility to develop cancer from workplace chemical exposures. The case in Feint is the genetic polymorphism for N-acetyltransferase activity and the risk of bladder cancer in workers exposed to carcinogenic arylamines. The acetyltransferase polymorphism is related to the metabolic activat ion and deactivation of carcinogenic arylamines. Any genetic screening test for cancer susceptibility must be based upon sound science. For example, it must be demonstrated that a specific metabolic phenotype i s a risk factor for cancer and, further, that the available tests accu rately classify the subjects as to the phenotype. If there is a poor c orrespondence between phenotype and genotype, or a large intra-individ ual variability in phenotype, misclassification may result. Also, bias , arising as a consequence of enzyme induction by specific substrates, must be ruled out. Genetic screening of workers for susceptibility to cancer seems to us an ethically unacceptable and premature, applicati on of the science. The use of the N-acetyltransferase polymorphism as a marker for susceptibility illustrates these drawbacks: (1) discrimin ation between polymorphic phenotypes is generally straightforward, but misclassification, to some degree, cannot be avoided; (2) although th e N-acetyltransferase phenotype is a useful predictor of susceptibilit y, evidence linking specific N-acetyltransferase polymorphisms with ca ncer risk is variable, depending on the exposure and population; (3) t he decisional autonomy of workers is violated if the test is used as a screen for employment; (4) scientifically and ethically primary preve ntion is more defensible than genetic or other screening; (5) the pote ntial for restriction of employment possibilities based on gender, rac e or ethnic group associated with this polymorphism is considerable, a nd needs evaluation.