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Scientific and ethical aspects of genetic screening of workers for cancer risk: The case of then-acetyltransferase phenotype

Authors
Journal
Journal of Clinical Epidemiology
0895-4356
Publisher
Elsevier
Publication Date
Volume
48
Issue
2
Identifiers
DOI: 10.1016/0895-4356(94)00131-9
Disciplines
  • Biology
  • Chemistry
  • Economics
  • Medicine
  • Philosophy

Abstract

Abstract Our expanding capacity to detect human genetic susceptibility to various chronic diseases presents us with the opportunity to screen asymptomatic people for purposes of employment, insurance or credit. It also brings with it the responsibility of deciding the ethical and social value of such applications. This paper addresses scientific and ethical issues involved in the use of genetic screening techniques which intend to identify individuals that have more than average susceptibility to develop cancer from workplace chemical exposures. The case in point 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 activation 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 is a risk factor for cancer and, further, that the available tests accurately classify the subjects as to the phenotype. If there is a poor correspondence between phenotype and genotype, or a large intra-individual 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, application of the science. The use of the N-acetyltransferase polymorphism as a marker for susceptibility illustrates these drawbacks: (1) discrimination between polymorphic phenotypes is generally straightforward, but misclassification, to some degree, cannot be avoided; (2) although the N-acetyltransferase phenotype is a useful predictor of susceptibility, evidence linking specific N-acetyltransferase polymorphisms with cancer risk is variable, depending on the exposure and population; (3) the decisional autonomy of workers is violated if the test is used as a screen for employment; (4) scientifically and ethically primary prevention is more defensible than genetic or other screening; (5) the potential for restriction of employment possibilities based on gender, race or ethnic group associated with this polymorphism is considerable, and needs evaluation.

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