Genetic testing in the NHS

 

Who is offered a genetic test? How does it work?

Genetic testing involves the analysis of the DNA (genetic code) contained in a few drops of blood. It is an expensive and time-consuming process.

So far, only a few of the genes involved in hereditary cancer have been found and can be tested for. These genes affect bowel/womb cancer and breast/ovarian cancer.

If you have a number of cases of any other type of cancer in your family, there probably won't be a genetic test available to you. However, you might be offered the chance to take part in research programmes in which scientists are trying to identify more cancer genes or are testing ways of preventing cancer. Your blood sample might also be kept by the laboratory, so that it can be tested for genetic changes that might be identified in the future. You will be asked whether you agree to your blood being stored.

You won't be offered genetic testing if you only have one (or sometimes even two) elderly relatives with breast or bowel cancer. Both breast and bowel cancer are common cancers, which mostly occur for reasons that are not fully understood, but aren't clearly linked to a cancer susceptibility gene. It is only likely that your family has inherited a cancer susceptibility gene if you have more than two, fairly young (under 60 years) relatives with these cancers on the same side of your family.

However, your family might be offered genetic testing, if, on the basis of your family history, it looks as though some of your family members might carry one of the known cancer susceptibility genes.

Genetic testing is a two-step process

• First, the laboratory has to try to find the particular changed gene (mutation) that might run in your family. This step is called the mutation search. In order to find this gene change, a member of your family who has been diagnosed with cancer has to be tested. The test involves taking a blood sample. This can be arranged in your own clinic or by your relative's GP. A mutation search is like trying to find a single spelling mistake in a big book. It involves reading the whole (or large parts) of the gene.

• After the particular mutation that runs in your family has been found, testing can be offered to other family members. They may want to know whether they too have inherited this family mutation and therefore have an increased risk of getting the same cancer. This test is called genetic screening or predictive or predispositional testing. This second step is a lot easier. Once a particular spelling mistake has been identified in a book, it is easy to check whether other copies of the same book (ie the genes of other family members) have the same mistake or not, because the scientists know exactly where to look and what to look for.

Mutation searching in the NHS can take up to 12 months. Predictive testing is much faster, as the researchers already know what they are looking for.

You can only be offered predictive genetic testing if you have a living relative who has been diagnosed with cancer and is willing to be tested first. There is one exception to this rule: if you have Ashkenazi (eastern European Jewish) ancestry, you may be offered testing for the three most common mutations that have been found in this group, without a relative who has developed cancer being tested first.

What if a mutation is found?

If a mutation is found (this is called a positive test result), the person has inherited a genetic mutation that increases their risk of getting a specific cancer. They can also pass on the mutation to their children. A positive test does not usually mean that the person who has the mutation will definitely get cancer (there are one or two exceptions – for example see our section on familial adenomatous polyposis). But it significantly increases the likelihood of that person developing cancer during their lifetime.

The increase in risk varies according to the particular genetic mutation and the type of cancer it relates to. For example, 8 in 10 (80%) of women who have a mutation in one of the known breast cancer genes, BRCA1, and a strong family history of the disease, will develop breast cancer. This is a much higher risk than women in the general population have. Only one in ten (10%) of women who don't have a strong family history will develop breast cancer.

Some people with a strong family history decide to have a genetic test when they have already been diagnosed with cancer. If you already have cancer and you are found to be a mutation carrier, you have an increased risk of developing another new cancer. Some people decide to have more extensive surgery as part of their cancer treatment if they know that they have a cancer gene mutation. So, rather than having only a breast lump taken out, they might decide to have the whole breast, or even both breasts, removed (mastectomy). In the case of bowel cancer, the doctor might think it is best to remove a large part or the whole bowel, rather than just the tumour (see the section 'Living with a high cancer risk' for more details).

Other members of the family

If you are found to have a cancer gene mutation, other members of your family might have inherited the same genetic change that you have. Each of your children will have a 1 in 2 chance (50%) of inheriting the change from you. Other relatives might also be affected, because you share your genetic heritage with them. As medical test results are always confidential, no one but you can tell your relatives about your test result. You have to decide whether and who to tell about your test. Some other members of your family might decide to see a genetic counsellor to help them make decisions about their cancer risk.

As a general rule, children are not tested to see whether they might have inherited a genetic mutation that increases their cancer risk. Even if a child has inherited a genetic mutation, testing and counselling can wait until the child is an adult and can make their own decisions. This is because most familial bowel and breast cancers do not affect children. The exception to this is familial adenometous polyposis (FAP). This is a particular kind of bowel cancer that can start very early in life.

It is important to remember that having a cancer gene mutation is not your fault. No one is to blame for the genes they have inherited. Families dealing with genetic risk sometimes have feelings of guilt, blame or responsibility, but genes are distributed by chance. We are not to blame for our eye colour or height or whether we have inherited a cancer gene mutation.

The immediate effect of a positive test is that genetic counselling and predictive testing can be offered to other family members who might be carriers of the gene. This allows identification of other family members who have an increased risk of getting cancer, and those who do not. For this reason it is advisable to tell your relatives that you have had a test and that it is positive.

This is your decision to make and can be very difficult. Your genetic counsellor can talk through all the issues with you. Other people can help you to deal with the emotional issues that may arise. You can also call our helpline for support.

What if no mutation is found?

If no mutation is found, the test is said to be inconclusive. In most cases of genetic testing no mutation is found in any of the genes known to be involved in hereditary breast/ovarian or bowel/womb cancer, even if there is a strong family history. Figures vary but, overall, mutations are identified in only about 10–20% (10 to 20 out of 100) of samples. This does not mean that the family in question is not at increased risk. In fact, if there is a very strong family history of a certain cancer, doctors assume that the members of this family are at increased risk of that cancer type, even if the laboratory cannot find a specific genetic mutation.

There are several possible reasons for a test not showing a mutation (an inconclusive result):

• The test might have missed the mutation.
• Currently some NHS laboratories don't test the whole gene in question, but perhaps only about 60% of it. They often look only for the most commonly found mutations. So the mutation in a specific family could be on a part of the gene that the laboratory didn't look at. In the near future, better testing facilities will be available that will enable all NHS laboratories to analyse the DNA of the whole gene.
• There is a faulty gene in the family (which can be concluded from the family history), but the fault is contained in a gene that has not yet been identified.
• The cancer in the family or person isn't actually due to an inherited gene, and the several cases of cancer has occurred by chance or because there are genetic causes of cancer that we do not yet fully understand.

This uncertainty about inconclusive test results is the reason why the NHS doesn't automatically offer genetic tests to everyone who wants to be tested. If the test is inconclusive, which is very likely, it will be impossible to know what the test result means, ie which of the four reasons above applies.

Negative results of predictive testing

Once a mutation has been identified in the family and a family member is subsequently found not to carry that mutation, it is concluded that they do not have any increased risk of developing the cancer.

This does not mean that the person in question definitely won't get cancer. It means that they have not inherited the gene mutation that would have put them at a much higher risk of developing cancer. The person still has the same risk of getting cancer as everybody else in the general population. This is a much lower risk than for people who have one of the known cancer genes. So in this case (but only in this case) a negative test is good news.