Genetic Testing

What is genetic testing?

Genetic testing looks for specific changes (called variants) in a person’s genes. Genetic variants can have harmful, beneficial, neutral (no effect), or have unknown or uncertain effects on a person’s risk of developing disease. Harmful variants in some genes are known to be associated with an increased risk of developing cancer.

Genetic variants are common in many cancers. Most of the time, these gene variants are acquired during a person’s life due to damage caused by environmental factors, aging, or even by chance, and may only be present in some cells of the body (e.g. within a tumour or cancer). However, sometimes a person can be born with a gene variant in all the cells of their body because they have inherited this variant from their mother or father. These inherited gene variants are thought to contribute to about 5 to 10% of all cancers.

Cancer can sometimes appear to “run in families” even if it is not caused by an inherited gene variant. For example, a shared environment or lifestyle factor, such as tobacco use, can cause similar cancers to develop among family members. However, some families are suspected as having an inherited cancer susceptibility because of the particular pattern or rare type of cancer in the family, the presence of other clinical features, or younger ages of diagnosis than typically seen

Genes involved in many of the known inherited cancer susceptibility syndromes have been identified. Testing whether someone carries a harmful variant in one of these genes can confirm whether their cancer is or is not linked to a known inherited syndrome. Some of the known syndromes linked to an increased risk of sarcoma and soft-tissue tumours include:

1. Li-Fraumeni syndrome (TP53 gene)
2. Hereditary paraganglioma-phaeochromocytoma syndrome (SDHX genes etc)
3. Neurofibromatosis Type 1 (NF1) and Neurofibromatosis type 2 (NF2)
4. Familial Adenomatous Polyposis (APC gene)

It is likely that harmful variants in other genes that have not yet been identified are also playing a role in the development of sarcomas and soft-tissue tumours. Ongoing research into the genetic basis of these tumours aims to identify other relevant genes to better understand why these tumours develop.

What is the role of genetic counselling in genetic testing for an inherited cancer syndrome?

Genetic counselling is generally recommended both before and after performing any genetic testing. This process helps a person to decide if genetic testing is right for them, understand how likely it is that they have an inherited cancer syndrome and how this influences their cancer risks, current treatment or ongoing care options, as well as supporting the patient’s emotional adjustment to this information.

Specifically, a genetic counsellor and their supervising geneticist/genetics doctor will discuss:

• The appropriateness of genetic testing and potential harms and benefits of testing.
• The medical implications of positive, uninformative, and uncertain genetic test results.
• The psychological risks and benefits of genetic testing, including potential clarification of cancer risks or the impact of living with uncertain results or learning that you have an increased cancer risk .
• The risk of passing on a gene variant to children.
• The importance of sharing information about genetic test results with blood relatives to help them understand their own risks and recommendations.

How is genetic testing done?

Genetic testing for an inherited cancer syndrome is always most helpful if a member of the family who has had cancer is tested first. Most of the time, testing for inherited gene variants is performed on a blood sample. Sometimes the tumour tissue itself is tested (particularly if a harmful variant is not found in a blood test). The blood or tissue sample is sent to a laboratory that specialises in genetic testing. The laboratory isolates the genetic information (called DNA) from within the blood or cancer cells, and looks for any ‘spelling mistakes’ in the requested gene(s). Genetic testing can look at one specific gene, a ‘panel’ of several genes or sometimes all of a person’s genetic material (their genome). The laboratory returns the test results to the genetics service that requested the test and this information is then discussed with the patient and shared with any other doctors involved with the patient’s care. Depending on how many genes are tested, it usually takes several weeks or longer for genetic test results to become available.

What are some of the benefits of genetic testing for inherited cancer syndromes?

There can be benefits to genetic testing, regardless of whether or not a person has a gene variant detected.

• An informative negative test can provide the person with peace of mind that a harmful gene variant was not inherited.
• A positive test result provides the person an opportunity to understand and, in some cases, manage their cancer risks.
• For people who are already diagnosed with a cancer, results of genetic testing may help them make decisions about their treatment and understand their risk for other cancers.
• Genetic testing provides an opportunity for family members to learn about their own cancer risks, which in some cases can allow them to take steps to prevent a cancer.
• Opportunities for further genetic testing as part of research studies may help us to identify new genes related to inherited cancer risks in the future. As our understanding of these genes improve it may help us to better diagnose and treat these cancers.