Genetic Testing

Who is eligible for genetic testing in the UK?

The Department of Health reviewed eligibility for genetic testing for BRCA1/2 mutations recently and in 2015 new commissioning meant that women who had a 1 in 10 chance of carrying a BRCA mutation could be offered genetic testing.

This assessment is made on the basis of your family history i.e. pattern of types of cancer and ages of onset of cancer in the family.  If your family history includes features described in the above section, then your GP should refer you to see a clinical genetics team for this assessment.

This also now includes women diagnosed with the most common type of ovarian cancer: high grade epithelial ovarian cancer (non-mucinous types). These women should be offered the opportunity for BRCA testing. If you receive a diagnosis of one of the above types of ovarian cancer and are not being offered genetic testing, please contact the Ask Eve Specialist Nurse Service for advice.

For further details of the NICE criteria for genetic testing, surveillance and risk management for BRCA mutations, please see the Familial breast cancer: classification, care and managing breast cancer and related risks in people with a family history of breast cancer.

Undergoing Genetic Testing

Genetic testing is used to find out whether a person is carrying a specific altered gene (genetic mutation) that can cause certain types of cancers.  If you meet the criteria for genetic testing under NICE guidelines, you may be referred to a Genetic Counsellor or Clinical Geneticist who will discuss your family history with you.  If you have been diagnosed with certain types of breast or ovarian cancer, it is possible that your Oncologist or Surgeon may discuss genetic testing with you and arrange for this to be done. Genetic testing involves taking a sample of your blood which will be examined and tested in a genetics laboratory to look for a mutation.

If you are the first member of your family to be offered genetic testing for a BRCA or Lynch Syndrome mutation, it will be necessary to check the entire gene for mutations using a process called gene sequencing. This has to be done very carefully, and can take a long time compared with most other hospital laboratory tests.  The usual turnaround for this type of test can be up to 8 weeks.

If a mutation has already been identified in another member of your family, the testing process is shorter as your specific family mutation is already known and therefore the lab knows exactly what to look for.  This is called ‘Predictive testing’. The turnaround for this test is much shorter and often approximately 2-4 weeks.

Your Family History

Your Genetic Counsellor will talk through your family history with you and produce a detailed family tree or Pedigree.  It is useful to bring as much information as possible about both the male and female lines in your family.

Cancer Type General Population Risk BRCA 1 BRCA 2
Breast cancer 12.50% 65 – 80% 45 – 85%
Ovarian cancer 2.50% 44 – 60% (Risk increases significantly from the age of 40) 17 – 30% (Risk increases significantly from mid 40s)
Pancreatic cancer 1.40% ~2-3% 5%
Prostate cancer 12.50% Approximately the same as the general population risk 20 – 25%
Male breast cancer 0.10% Approximately the same as the general population risk 7%

What do my results mean?


Positive

If you are told that you carry a genetic mutation this means that you have inherited a known harmful mutation and, therefore, have an increased risk of developing certain cancers.  However, a positive test does not mean that you will definitely develop one or more of these cancers.  This test cannot predict who will or who will not develop a cancer. There are many people who have harmful BRCA mutations and do not go on to develop cancer.

A positive genetic test result carries important health and social implications for other family members, including future generations.  A genetic test not only informs you about your risk but also about the potential risks for your relatives and children. If you wish you can discuss these issues with your genetics team or cancer clinician. Other members of your family can also access genetic testing if you have been found to carry a mutation.

Men and women who inherit a mutation, whether or not they go on to develop cancer, may pass the mutation on to their sons and daughters.  Each child carries a 1 in 2 chance of inheriting a parent’s mutation.

Negative

If you are being tested for an identified genetic mutation that runs in your family and receive a negative test result, this means that you do not carry the same harmful mutation that is responsible for the cancers in the family, and therefore you cannot pass it on to your children.  This kind of test result is known as a true negative and you are thought to carry the same risk of cancer as anyone else of your age in the general population.  It is unlikely that you will be offered extra screening and you will start breast screening (like everyone else) on the National Breast Screening Programme when you reach 50 years old.

It is impossible for a mutation to skip a generation and therefore, if you test negative, your children will also test negative for your familial mutation.

There are some families who test negative for a BRCA or Lynch Syndrome mutation but whose family history has many cases of the associated cancers.  It is possible that members of these families carry a mutation in a gene that is yet to be identified.  If you fall into this category, you may still be offered increased screening and risk-reducing surgery (depending on your risk assessment). This is something to discuss with your treating doctor or genetics team.

Variant of Unknown significance

If you are told that your mutation falls under the category of  Variant of Unknown Significance or VUS this means that at the time of testing, the laboratory is unable to determine with certainty whether gene change is pathogenic, which increases your risk of developing cancer or benign, which does not increase your risk.  As genetic testing evolves, and the number of genes on hereditary cancer panel tests increases, so does the chance that people will receive a VUS result.  The laboratory will keep your blood or saliva sample because as time goes on, and more research is carried out, people whose test results are unclear may be contacted and informed that their sample has been retested and re classified as either pathogenic (cancer causing) or benign. Only a small proportion of VUS mutations get re-classified as pathogenic or cancer causing.

Screening and risk management options for those who have received a VUS result will be based on person/family history of cancer and more advice can offered by your genetics team.

It can at times be very unsettling being told that you carry a Variant of Unknown Significance as it is not clear whether your mutation will eventually lead to an increased risk of cancer. However, most VUS mutations are not pathogenic or cancer causing. It is important to discuss your family history in detail with your genetics team in order to make decisions regarding screening as opposed to surgery.