Science: The Truth About... Genetic Testing

THERE ARE more than 4,000 inherited disorders caused by defects in single genes. The DNA that we inherit, and the mutations and damage that arise in it during the course of a lifetime, also play a major role in most of today's biggest killers, such as cancer and heart disease. The age of the genetic test is upon us, and it is fast becoming a major new weapon in the armoury of modern medicine.

Genetic testing is also attracting the attention of life insurance companies, which see it as a legitimate source of information for assessing the life expectancy of new customers. Government advisers want access to this information to be strictly controlled until the predictive potential of genetic tests is fully evaluated. The Government itself responded to this recommendation today (see news, page 12).

Doctors carry out genetic tests for a variety of reasons, the main ones being if there is a family history of a specific illness, such as breast cancer or Huntington's disease, or if a patient begins to show symptoms of a genetic disorder. Tests can also be carried out if parents are concerned about passing on a genetic problem to their children. Foetuses can be tested for genetic faults if they are thought to be at risk.

There are two main types of genetic test. One examines the gene in question, which obviously has to be identified and thoroughly studied to determine what constitutes a mutation that would cause a given disorder. The second type of test uses a genetic "marker", which is a way of identifying a piece of DNA which is known to be very close to the particular gene or mutation. This is technically described as linkage analysis, and is an indirect way of testing someone when the gene itself has not yet been isolated.

At present, genetic tests are only used for specific illnesses caused by defects in single genes.

The most common test determines whether a person carries a copy of the defective gene for cystic fibrosis. One in 20 people is a carrier of cystic fibrosis. They are quite healthy, but if they have children with another carrier there is a one-in-four risk of giving birth to a baby with cystic fibrosis.

In the future it may be possible to develop tests for disorders that are influenced by more than one gene. This would give doctors a more accurate way of estimating a person's predisposition to illnesses such as heart disease and high blood pressure.

But a concern with any genetic test is knowing how accurate it is. Any laboratory procedure is prone to error and genetic testing is no exception. The interpretation of a result has to take into account the possibility of false positives and negatives, when the test wrongly identifies a person as either having the problem or being free of it.

The immense practical and ethical problems associated with genetic testing is exemplified by the tests for the two breast cancer genes BRCA1 and BRCA2. These genes are thought to suppress the growth of malignant tumours, and so any mutations in them increase the risk of developing the disease.

One difficulty is trying to estimate this increased risk. Initially, when BRCA1 was first discovered, it was thought that a woman with a mutation in that gene had an 85 per cent higher risk of developing breast cancer and a 60 per cent higher risk of ovarian cancer over her lifetime. More recent studies suggest these risks may be much lower, about 56 per cent for breast cancer and 16 per cent for ovarian cancer.

These estimates, furthermore, only apply to the small proportion of women where breast cancer runs in the family. A negative test merely indicates that a woman does not have the mutation concerned. It is no guarantee that she will not develop the cancer for other reasons, such as long- term exposure to oestrogenic hormones. Genes do not tell the whole story and, for the moment at least, genetic testing remains a rather inexact science.