Testing for susceptibility to hazardous chemicals or radiation

People vary in their responses to hazardous chemicals. How any particular individual responds depends on many non-genetic factors such as age, weight, gender, diet, lifestyle (especially smoking), but can also be influenced by a person's genes1.

Whether a chemical is hazardous to health depends on2:

  • its concentration in the body;
  • how it is distributed round the body;
  • which organs are affected;
  • how quickly it is broken down and whether it is broken down into a harmless substance or another toxic product;
  • how quickly it can be excreted from the body.

Many of these processes are dependent on enzymes (molecules that affect the speed of chemical reactions in the body) and other signalling molecules that are encoded by our genes. In this way, genetic variations can lead to differences in the way people react to the same toxin. For example, people who are slow ‘detoxifiers' are more likely to be affected than people who can break down toxins more quickly, simply because they are exposed to the chemical for longer3.

When chemicals are broken down in the body, the products are usually inactive and therefore easily excreted. However, the products are sometimes more reactive and able to bind to genetic material (DNA) or other biologically important molecules. If the DNA adducts (chemicals bound to the DNA) are not eliminated by the body's natural repair processes, it is thought they can cause gene mutations which can eventually lead to cancer4.

Genetic tests that aim to identify individuals who are at high risk from exposure to hazardous chemicals fall into three categories. These tests all identify genetic differences that people are born with.

The first category includes tests for differences in the way people break down toxins. This involves testing for faults in the genes that encode enzymes which carry out the breakdown process. These kinds of tests are available now.

The second category relates to genetic differences in the way individuals respond to the damage caused by chemicals and involves testing for faults in DNA repair processes. These genes are still being researched.

The third category examines differences in the genetic make-up of our immune systems, based on the theory that these differences will affect individual susceptibility to occupational-linked asthma. Again, this research is still in its early stages.

It is claimed that the use of these genetic tests will enable those who are most at risk from hazardous chemicals to avoid workplace exposure. However, it is questionable whether the tests can really be used in this way. It seems they are unlikely to deliver real benefits for either employers or employees and are more likely to result in genetic discrimination5.

Case study: the PON1 gene and susceptibility to pesticides

Research on genetic susceptibility to organophospate (OP) pesticides (such as sheep dip) has suggested that a number of genes may play a role, particularly a gene called PON1. Some recent research on PON1 and sheep dip has been funded by the UK Health and Safety Executive (HSE) at the University of Manchester:6

This type of research can help improve worker safety by improving understanding of how sensitivity to pesticides develops. But it could also be used to argue for the exclusion of “genetically susceptible” workers. However, a detailed study has concluded that the health benefit of genetically screening pesticide workers would be limited and could be harmful and unethical. This is because:7

  • the predictive value of the test is limited;
  • many other factors are likely to influence whether a pesticide worker becomes ill;
  • alternative approaches (such as reducing exposures or monitoring health) may be better for health.
  1. Levy LS. Variability and susceptibility to occupational and environmental contaminants. In Institute for Environment and Health, ed. Variability and susceptibility in human response to occupational exposure to chemicals in the UK (Report R13), pp 48-57. Leicester, UK: MRC Institute for Environment and Health, 2002.
  2. Nakajima T, Aoyama T. Polymorphism of drug-metabolising enzymes in relation to individual susceptibility to industrial chemicals. Industrial Health 2000; 38: 143-52.
  3. Vineis P, Schulte PA. Scientific and ethical aspects of genetic screening of workers for cancer risk: the case of the N-acetyltransferase phenotype. Journal of Clinical Epidemiology 1995; 48: 189-97.
  4. Koh D, Seow A, Ong CN. Applications of new technology in molecular epidemiology and their relevance to occupational medicine. Occupational and Environmental Medicine 1999; 56: 725-9.
  5. Genetic Testing in the Workplace (2003) GeneWatch UK.
  6. http://www.hse.gov.uk/research/rrpdf/rr408.pdf .
  7. http://depts.washington.edu/ceeh/issues/PON.pdf

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