Cancer Genetic Testing
What Is Cancer Genetic Testing?
Cancer genetic testing is a specialised form of genetic testing that looks for inherited changes in genes that may increase a person’s likelihood of developing certain types of cancer. These genetic changes, sometimes called pathogenic or likely pathogenic variants, can be passed from one generation to another and may contribute to hereditary cancer syndromes.
Testing may examine a specific gene, a group of cancer-associated genes, or a broader set of genes, depending on the personal and family history and the clinical question being investigated. Commonly assessed genes include BRCA1 and BRCA2, as well as other genes associated with hereditary breast, ovarian, bowel, prostate and other cancers.
Cancer genetic testing is different from testing a tumour for genetic changes acquired during cancer development. Inherited cancer genetic testing examines DNA that is present in the body’s cells and can therefore provide information about hereditary cancer risk and, in some circumstances, information that may be relevant to biological relatives.
The appropriate test depends on the individual’s circumstances, including any previous cancer diagnosis, the types of cancer occurring in the family, the ages at which cancers were diagnosed, and whether a genetic variant has already been identified in a relative.
What Does Cancer Genetic Testing Look For?
Cancer genetic testing looks for inherited changes in genes that can increase a person’s likelihood of developing certain types of cancer. These changes are present in the DNA of the body’s cells and may be passed from a biological parent to a child.
The genetic changes identified through testing may include pathogenic or likely pathogenic variants that are associated with an increased risk of hereditary cancer. The test may also identify a variant of uncertain significance (VUS), where there is currently not enough evidence to determine whether the genetic change affects cancer risk.
Depending on the clinical question, testing may examine one specific gene or multiple genes associated with hereditary cancer. The genes investigated are selected according to factors such as the individual’s personal cancer history, family history and the pattern of cancers within the family.
Importantly, finding an inherited genetic variant does not mean that a person will definitely develop cancer. Rather, the result can provide information about inherited cancer susceptibility that may help inform appropriate risk assessment, screening and other clinical management.
Cancer genetic testing focuses on inherited genetic changes. This is different from somatic genomic testing, which examines genetic changes acquired by cancer cells during a person’s lifetime and is used for different clinical purposes.
When Is Cancer Genetic Testing Recommended?
Cancer genetic testing may be recommended when a person’s personal or family history suggests an increased likelihood of an inherited cancer predisposition. The decision is based on the overall pattern of cancer in the family rather than on the presence of cancer in one relative alone.
Genetic testing may be considered when there is:
- A cancer diagnosis at a younger-than-expected age
- A personal history of more than one primary cancer
- Several close biological relatives with the same or related types of cancer
- A combination of cancers within a family that may be associated with a hereditary cancer syndrome
- A rare cancer or cancer type that can be associated with an inherited genetic predisposition
- A known pathogenic or likely pathogenic variant associated with hereditary cancer in the family
- A personal or family history suggesting an inherited cancer risk based on the pattern, number or age of cancer diagnoses
Testing may also be recommended for someone who has already been diagnosed with cancer when identifying an inherited genetic variant could provide information relevant to their own care or help determine whether biological relatives may also be at increased risk.
Where possible, genetic testing is often most informative when it begins with a family member who has had a cancer relevant to the suspected hereditary syndrome. If a pathogenic or likely pathogenic variant is identified, other relatives can then be offered targeted testing for the known familial variant where appropriate.
The presence of a family history of cancer does not automatically mean that genetic testing is necessary. A specialist assessment of the personal and family history can help determine whether testing is appropriate and which genetic test is most relevant.
Which Cancers Can Be Associated With Inherited Genetic Changes?
Inherited genetic changes can increase the risk of developing certain types of cancer and may be associated with hereditary cancer syndromes. The table below shows examples of cancers that can be linked to inherited genetic variants and some of the genes or syndromes commonly considered in hereditary cancer assessment.
| Cancer Type | Examples of Associated Genes or Syndromes | When Inherited Risk May Be Considered |
|---|---|---|
| Breast Cancer | BRCA1, BRCA2, PALB2, TP53 and other hereditary cancer genes | Particularly when breast cancer occurs at a younger age, affects both breasts, occurs alongside related cancers, or there is a strong family history. |
| Ovarian and Fallopian Tube Cancer | BRCA1, BRCA2 and genes associated with hereditary breast and ovarian cancer | May be considered when ovarian cancer or related cancers occur in the individual or family, particularly where the pattern suggests hereditary risk. |
| Bowel and Colorectal Cancer | MLH1, MSH2, MSH6, PMS2, EPCAM and APC | May be considered when bowel cancer occurs at a younger age, there are multiple affected relatives, or the family history suggests Lynch syndrome or another inherited condition. |
| Prostate Cancer | BRCA1, BRCA2, ATM, CHEK2 and other hereditary cancer genes | May be considered particularly where prostate cancer is diagnosed at a younger age or there is a family history of prostate, breast, ovarian or pancreatic cancer. |
| Pancreatic Cancer | BRCA1, BRCA2, PALB2, ATM and other hereditary cancer genes | May be considered when pancreatic cancer occurs alongside a relevant personal or family history of hereditary cancer. |
| Endometrial Cancer | MLH1, MSH2, MSH6, PMS2 and EPCAM, particularly in Lynch syndrome | May be considered when endometrial cancer occurs at a younger age or alongside colorectal and other Lynch syndrome-associated cancers in the family. |
These are examples rather than an exhaustive list. The genes considered for cancer genetic testing depend on the individual's personal and family history, the cancers involved and the hereditary cancer syndrome being investigated.
Who May Benefit From Cancer Genetic Testing?
Cancer genetic testing may be useful for people whose personal or family history suggests that they could have an inherited predisposition to cancer. The potential value of testing depends on the pattern of cancer within the family, the age at which cancers were diagnosed and whether a hereditary cancer-related genetic variant has already been identified.
People who may benefit from cancer genetic testing include those who:
- Have been diagnosed with cancer at a younger-than-expected age
- Have had more than one primary cancer during their lifetime
- Have several close biological relatives who have had the same or related cancers
- Have a family history involving cancers commonly associated with hereditary cancer syndromes
- Have a known pathogenic or likely pathogenic variant associated with hereditary cancer in the family
- Have a personal or family history that suggests an inherited cancer predisposition despite there being no single obvious pattern
People who have already been diagnosed with cancer may also benefit from testing when identifying an inherited genetic variant could provide information relevant to their ongoing care or help identify relatives who may have an increased cancer risk.
Family members may benefit from testing when a hereditary cancer-related variant has already been identified in a relative. In this situation, testing can determine whether the same inherited variant is present, which may help clarify whether the relative has an increased risk associated with that particular genetic change.
Having a relative with cancer does not necessarily mean that genetic testing is appropriate. A specialist assessment of the personal and family history can help determine whether testing is indicated and which approach is most relevant.
What Genes Are Commonly Tested for Hereditary Cancer?
Hereditary cancer genetic testing may examine one or several genes associated with an increased inherited risk of cancer. The genes included in a test depend on your personal and family history, the types of cancer involved and the hereditary cancer syndrome being considered.
BRCA1 and BRCA2 are among the best-known hereditary cancer genes. Pathogenic variants in these genes can increase the risk of breast, ovarian, prostate and pancreatic cancers, although the level of risk varies between individuals and according to the gene involved.
Lynch syndrome is associated with inherited changes in mismatch repair genes including MLH1, MSH2, MSH6 and PMS2, as well as EPCAM. These genes are associated with increased risks of colorectal, endometrial and several other cancers.
Other genes may be considered depending on the clinical history. For example, PALB2 is associated with hereditary breast cancer risk, while TP53 is associated with Li-Fraumeni syndrome and an increased risk of several cancer types.
Depending on the personal and family history, testing may also include genes such as ATM and CHEK2, as well as other genes associated with hereditary cancer predisposition. The appropriate genes depend on the cancers occurring in the family and the suspected underlying syndrome.
When more than one hereditary cancer syndrome could explain the family history, a multigene panel may be used to analyse several relevant genes at the same time. Broader testing can provide useful information but may also identify variants whose clinical significance is uncertain.
There is no single set of genes that is appropriate for everyone. The choice of genes for hereditary cancer testing should be guided by the personal and family history and the specific clinical question. Testing may focus on one gene or include a broader panel when several genes are relevant.
How Is Cancer Genetic Testing Performed?
Cancer genetic testing is usually performed using a sample of blood or saliva. The sample contains DNA that can be analysed to look for inherited genetic changes associated with hereditary cancer risk.
Blood Testing
For a blood test, a small sample of blood is collected and sent to a specialist laboratory. DNA is extracted from the sample and analysed for genetic variants in the genes included in the selected test.
Saliva Testing
Some hereditary cancer genetic tests can be performed using a saliva sample. Saliva provides cells containing DNA that can be extracted and analysed in a similar way. Whether saliva is suitable depends on the specific test and laboratory requirements.
Laboratory Genetic Analysis
The laboratory analyses the relevant gene or genes using an appropriate genetic testing method. Depending on the test, this may involve sequencing and additional analysis to identify genetic variants that could affect cancer susceptibility.
The laboratory findings are then classified according to their current clinical significance. Results may identify a pathogenic or likely pathogenic variant, no relevant pathogenic variant, or a variant of uncertain significance (VUS). The interpretation depends on the available scientific and clinical evidence.
The testing method and genes analysed are selected according to the individual’s personal and family history and the specific hereditary cancer question being investigated. A specialist can explain which sample and testing approach are most appropriate in each case.
What Happens During Cancer Genetic Testing?
Cancer genetic testing usually involves several steps, beginning with a review of your personal and family history and ending with a discussion of the test results. The exact process can vary depending on the type of test and the clinical question being investigated.
Review of Your Personal and Family History
A specialist will usually ask about previous cancer diagnoses, the types of cancer occurring in your biological relatives, the ages at which they were diagnosed and any genetic test results already available within the family. This information helps determine whether hereditary cancer testing is appropriate and which genes should be considered.
Selecting the Appropriate Genetic Test
Based on the information collected, the appropriate testing approach can be selected. This may involve testing a single gene, several genes associated with a particular hereditary cancer syndrome or a broader multigene panel. If a known familial variant has already been identified, targeted testing for that specific variant may be appropriate.
Providing a DNA Sample
Once the testing approach has been agreed, a DNA sample is collected, usually using a blood or saliva sample depending on the test and laboratory requirements. The sample is then sent to a specialist laboratory for genetic analysis.
Receiving and Reviewing Your Results
Once the laboratory analysis is complete, the results are reviewed in the context of your personal and family history. The result may identify a pathogenic or likely pathogenic variant, may not identify a clinically relevant inherited variant, or may identify a variant of uncertain significance (VUS).
The significance of the result depends on the genetic finding, the test performed and the wider clinical context. Your specialist can explain what the result means for your cancer risk and whether any further assessment, screening or testing for biological relatives should be considered.
The testing process is therefore more than simply providing a DNA sample. Careful assessment before testing and appropriate interpretation afterwards are important parts of hereditary cancer genetic testing.
How Are Cancer Genetic Test Results Interpreted?
Cancer genetic test results are interpreted by considering the genetic finding alongside the test performed, personal cancer history and family history. A result can provide information about inherited cancer risk, but it does not by itself confirm whether cancer will develop. Different types of results have different clinical meanings and may require different follow-up.
Pathogenic or Likely Pathogenic Variant
A pathogenic or likely pathogenic variant can indicate an inherited predisposition to certain cancers. The level of risk depends on the gene and specific variant involved, as well as other individual factors. The result may support discussions about appropriate screening, risk-reduction options and testing for biological relatives.
Negative Result
A negative result means that no relevant pathogenic or likely pathogenic variant was identified in the genes examined. However, it does not necessarily mean that inherited cancer risk is absent. Personal and family history may still indicate an increased risk, particularly when no known familial variant has been identified.
Variant of Uncertain Significance (VUS)
A VUS is a genetic change for which there is currently insufficient evidence to determine whether it affects cancer risk. A VUS is not treated in the same way as a pathogenic variant and should not normally be used on its own to guide major medical decisions. Its classification may be updated as scientific evidence develops.
Interpreting Results in Context
The meaning of a cancer genetic test result depends on the wider clinical picture. Your personal and family history, the genes analysed and any previously identified familial variant may all affect how the result is interpreted and what follow-up may be appropriate.
What Happens After a Hereditary Cancer Risk Is Identified?
If cancer genetic testing identifies a pathogenic or likely pathogenic variant associated with hereditary cancer risk, the result can help guide appropriate follow-up. The next steps depend on the gene involved, the associated cancer risks, the individual’s personal and family history and whether cancer has already been diagnosed.
Reviewing Cancer Risk
A specialist can explain which cancers are associated with the identified genetic variant and how the finding may affect the individual’s estimated risk. This information should be considered alongside personal and family history rather than interpreted in isolation.
Considering Screening and Surveillance
Depending on the genetic finding, earlier, more frequent or specialised cancer screening may be recommended. The appropriate surveillance programme varies between hereditary cancer syndromes and should be tailored to the individual’s circumstances.
Discussing Risk-Reduction Options
For some hereditary cancer conditions, additional measures may be considered to reduce cancer risk. These can include changes to screening strategies and, in selected circumstances, preventive or risk-reducing procedures. The appropriate options depend on the specific genetic finding and individual preferences.
Considering Testing for Biological Relatives
When an inherited pathogenic or likely pathogenic variant is identified, biological relatives may have the option of testing for the same familial variant. Targeted testing can help determine which relatives have inherited the variant and may therefore benefit from appropriate risk assessment or surveillance.
If you have been diagnosed with cancer, an inherited genetic finding may also provide information that is relevant to aspects of your ongoing care. Any treatment decisions should be made with the appropriate oncology and clinical teams based on the complete clinical picture.
A hereditary cancer risk does not mean that cancer is certain to develop. Instead, identifying an inherited genetic variant can provide an opportunity to understand risk more clearly and consider appropriate screening and follow-up for the individual and, where relevant, their family.
Cancer Genetic Testing and Genetic Counselling
Genetic counselling can be an important part of the cancer genetic testing process. It helps individuals understand why testing may be considered, what the test can and cannot tell them, and how the results may affect them and their biological relatives.
Before Cancer Genetic Testing
Before testing, a genetic specialist may review your personal and family history and discuss the possibility of an inherited cancer predisposition. This can help determine whether genetic testing is appropriate and which genes or testing approach may be most relevant.
Understanding the Possible Results
Genetic counselling can also help prepare you for the different types of results that may be reported, including a pathogenic or likely pathogenic variant, a negative result or a variant of uncertain significance (VUS). Understanding these possibilities can help set realistic expectations before testing.
After Receiving Your Results
Following testing, the result can be considered alongside your personal and family history to determine what it may mean for your cancer risk and whether further screening, risk assessment or testing for biological relatives should be considered.
Genetic counselling may also provide an opportunity to discuss the emotional, family and practical implications of learning about an inherited cancer risk. The appropriate support depends on the individual’s circumstances and the result identified.
To learn more about the role of counselling throughout the testing process, see our genetic counselling service.
Cancer Genetic Testing for Families and Relatives
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A Result May Have Family Implications: A pathogenic or likely pathogenic variant associated with hereditary cancer may also be relevant to biological relatives because inherited genetic changes can be passed from one generation to another.
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Testing Close Biological Relatives: When a known hereditary cancer-related variant has been identified in the family, close biological relatives may be offered testing to determine whether they have inherited the same genetic change.
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Targeted Familial Variant Testing: If the specific familial variant is already known, relatives can often be tested specifically for that genetic change rather than undergoing a broader cancer genetic test.
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Risk Assessment and Screening: Relatives who have inherited a clinically significant genetic variant may benefit from appropriate cancer risk assessment and screening based on the associated hereditary cancer syndrome.
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Understanding a Negative Familial Result: A relative who has not inherited a known familial pathogenic or likely pathogenic variant may not have the increased inherited risk associated with that particular variant, although their personal and family history may still be relevant.
One genetic result can provide important information for an entire family. When a hereditary cancer-related variant is identified, appropriate testing and risk assessment for biological relatives can help clarify who may benefit from further screening or follow-up.
Frequently asked questions
In this section you can check frequently asked questions.
What is cancer genetic testing?
Cancer genetic testing looks for inherited genetic changes that may increase a person’s likelihood of developing certain types of cancer. It can help identify hereditary cancer predisposition and may provide information relevant to the individual and their biological relatives.
Does a positive cancer genetic test mean I will develop cancer?
No. A pathogenic or likely pathogenic variant can indicate an increased risk of certain cancers, but it does not mean that cancer will definitely develop. The level of risk depends on the gene, the specific variant and other individual factors.
What cancers can be linked to inherited genetic changes?
Inherited genetic variants can be associated with several cancers, including breast, ovarian, colorectal, prostate, pancreatic and endometrial cancers. The relevant genes depend on the suspected hereditary cancer syndrome and the individual’s personal and family history.
What sample is used for cancer genetic testing?
Hereditary cancer genetic testing is commonly performed using a blood or saliva sample. The appropriate sample depends on the specific test and laboratory requirements.
Can cancer genetic testing be done if I have already had cancer?
Yes. People who have already been diagnosed with cancer may be offered inherited cancer genetic testing when their personal or family history suggests a hereditary cancer predisposition or when the result could provide information relevant to their care or biological relatives.
What does a negative cancer genetic test mean?
A negative result means that no relevant pathogenic or likely pathogenic variant was identified in the genes examined. It does not always eliminate inherited or familial cancer risk, particularly when no known familial variant has been identified.
What is a variant of uncertain significance (VUS)?
A VUS is a genetic change for which there is currently insufficient evidence to determine whether it affects cancer risk. A VUS is not equivalent to a positive result and should not normally be used on its own to guide major medical decisions.
Should my family members have cancer genetic testing?
If a pathogenic or likely pathogenic variant associated with hereditary cancer has been identified in a family, biological relatives may be able to have targeted testing for the same familial variant. Whether testing is appropriate depends on the specific genetic finding and each relative’s circumstances.
How long does cancer genetic testing take?
The time required depends on the type of genetic test and the laboratory performing the analysis. Your specialist or testing provider can explain the expected timeframe for receiving the results before the test is arranged.
Is cancer genetic testing the same as tumour genetic testing?
No. Hereditary cancer genetic testing looks for inherited genetic changes that are present in the body’s cells. Tumour or somatic genomic testing examines genetic changes acquired by cancer cells and is used for different clinical purposes.
Discuss Cancer Genetic Testing With a Specialist
Cancer genetic testing can help clarify whether an inherited genetic variant may contribute to an increased risk of certain cancers. The most appropriate testing approach depends on your personal and family history, the cancers involved and any genetic findings already identified within your family.
Choose the Right Testing Approach
At London Genetics, cancer genetic testing is considered in the context of your individual circumstances. Whether you have been diagnosed with cancer, have a strong family history or have a known familial genetic variant, the aim is to identify the most appropriate testing pathway for the clinical question being investigated.
Understand Your Results and Next Steps
Once testing has been completed, your result can be considered alongside your personal and family history. Depending on the findings, this may help inform appropriate cancer screening, risk assessment or testing for biological relatives.
Considering cancer genetic testing? Book an appointment with London Genetics to discuss your personal or family history and the most appropriate testing pathway for you.
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