What Is Ovarian Cancer Genetic Testing?
Ovarian cancer genetic testing is a type of genetic test used to identify inherited genetic variants that may increase a person’s risk of developing ovarian cancer. These variants are known as germline variants because they are present in the DNA of cells throughout the body and can be inherited from a biological parent.
Genetic testing for ovarian cancer is particularly relevant because some ovarian cancers are associated with inherited changes in genes involved in DNA repair and cancer susceptibility. Identifying a pathogenic or likely pathogenic variant can provide information about a person’s inherited cancer risk and, where relevant, may also have implications for biological relatives.
Ovarian cancer genetic testing can be considered both for people who have been diagnosed with ovarian cancer and for individuals whose personal or family history suggests an increased likelihood of an inherited cancer predisposition. For someone already diagnosed with ovarian cancer, identifying an inherited genetic variant may have implications for the management of the current cancer, future cancer risks and assessment of relatives.
It is important to distinguish genetic testing from tests used to diagnose ovarian cancer itself. Genetic testing examines DNA for inherited variants associated with cancer susceptibility; it does not by itself diagnose whether someone currently has ovarian cancer.
Genetic testing may involve analysing one specific gene or several genes at the same time through a multigene panel. The appropriate testing approach depends on the individual’s clinical circumstances, personal and family history, and any relevant findings from tumour testing.
Inherited genetic variants are different from genetic changes that develop only within cancer cells during a person’s lifetime. These acquired, or somatic, changes are not normally inherited and do not by themselves indicate that other family members carry the same variant. In some situations, tumour testing may identify a finding that needs to be investigated further with germline testing to determine whether it is inherited.
The purpose of ovarian cancer genetic testing is therefore not simply to determine whether a person will develop cancer. It can provide clinically relevant information about inherited cancer susceptibility, help inform appropriate medical management and, when an inherited pathogenic variant is identified, help determine whether genetic testing may be relevant for biological relatives.
When Is Genetic Testing Considered for Ovarian Cancer?
Genetic testing for ovarian cancer may be considered when a person’s personal or family history, cancer diagnosis, or other clinical findings suggest that an inherited genetic variant could be relevant. Testing is not limited to people with a strong family history, as some ovarian cancer diagnoses may themselves provide a reason to consider germline genetic testing.
Genetic testing is based on clinical circumstances. The decision to test depends on the type of ovarian cancer, personal and family history, known familial variants and other relevant clinical findings. Genetic testing may provide information about inherited cancer risk for both the individual and biological relatives.
Germline Genetic Testing for Ovarian Cancer
Germline genetic testing for ovarian cancer looks for inherited genetic variants that are present in the DNA of cells throughout the body. These variants are inherited from a biological parent and can increase the risk of developing ovarian cancer and, depending on the gene involved, other types of cancer.
For ovarian cancer, germline testing is an important part of assessing whether an inherited genetic predisposition may be contributing to a person’s cancer risk. In people diagnosed with certain types of ovarian cancer, genetic testing may also provide information that is relevant to the management of the current cancer as well as the assessment of biological relatives.
Germline genetic testing is usually performed using a blood sample, although saliva or other suitable samples may also be used. Because an inherited variant is present throughout the body, it can be detected in DNA obtained from these samples. The laboratory analyses selected genes for pathogenic or likely pathogenic variants associated with hereditary ovarian cancer risk.
Testing may examine one specific gene when there is a known familial variant or a strong clinical reason to focus on a particular gene. In other circumstances, a multigene panel may be used to analyse several ovarian cancer susceptibility genes at the same time. The choice of testing approach depends on the individual’s clinical circumstances, personal and family history and, where relevant, previous tumour findings.
A pathogenic or likely pathogenic germline variant can have implications beyond the individual being tested. Because inherited variants can be passed between biological relatives, identifying such a variant may allow appropriate family members to be offered targeted genetic testing for the known familial variant.
It is also important to understand that germline testing and tumour testing are not interchangeable. Germline testing is designed to identify inherited variants, whereas tumour testing examines genetic changes found in cancer cells. In some situations, a finding identified through tumour testing may need to be followed by germline testing to determine whether the variant was inherited. This distinction is particularly important when interpreting genetic findings in someone who has already been diagnosed with ovarian cancer.
Germline genetic testing therefore provides information about inherited cancer susceptibility rather than simply identifying whether ovarian cancer is present. The result needs to be interpreted in the context of the individual’s diagnosis, personal and family history and the genes included in the test.
Which Genes Are Tested for Ovarian Cancer?
Ovarian cancer genetic testing may include several genes associated with inherited ovarian cancer susceptibility. The genes included depend on the individual’s clinical circumstances and the type of genetic test being performed. Multigene panels are commonly used to assess several relevant genes at the same time rather than focusing only on BRCA1 and BRCA2. Current NHS genomic guidance includes genes such as BRCA1, BRCA2, PALB2, RAD51C, RAD51D, BRIP1, MLH1, MSH2 and MSH6 in germline testing for relevant ovarian cancers.
| Gene | Main hereditary association | Relevance to ovarian cancer testing |
|---|---|---|
| BRCA1 | Hereditary breast and ovarian cancer | One of the most important genes associated with inherited ovarian cancer susceptibility. |
| BRCA2 | Hereditary breast and ovarian cancer | A major inherited cancer susceptibility gene that can be included in ovarian cancer genetic testing. |
| PALB2 | Hereditary breast and ovarian cancer susceptibility | May be included in multigene panels assessing inherited ovarian cancer susceptibility. |
| RAD51C | Hereditary ovarian and breast cancer susceptibility | Associated with inherited ovarian cancer susceptibility and included in relevant multigene panels. |
| RAD51D | Hereditary ovarian and breast cancer susceptibility | Associated with inherited ovarian cancer susceptibility and may be analysed as part of a multigene panel. |
| BRIP1 | Hereditary ovarian cancer susceptibility | May be included when assessing inherited susceptibility to ovarian cancer. |
| MLH1 | Lynch syndrome | Associated with inherited susceptibility to several cancers, including ovarian cancer. |
| MSH2 | Lynch syndrome | May be relevant when ovarian cancer is associated with Lynch syndrome. |
| MSH6 | Lynch syndrome | May be included in germline testing where Lynch syndrome is clinically relevant. |
These are not the only genes that may be relevant to ovarian cancer genetic testing. The appropriate panel depends on the individual’s personal and family history, cancer diagnosis and clinical assessment. Some of these genes are also associated with inherited risks for other cancer types. For a broader overview of cancers associated with inherited genetic changes, see our Genetics Related Cancers guide.
What Can Ovarian Cancer Genetic Test Results Show?
Ovarian cancer genetic testing can produce several different types of results, depending on the genes analysed and the genetic variants identified. A result may show a pathogenic or likely pathogenic variant, no relevant pathogenic variant, or a variant of uncertain significance (VUS).
A pathogenic or likely pathogenic variant means that a genetic change associated with an increased risk of cancer has been identified. When this finding is present in the germline, it indicates an inherited genetic predisposition and may have implications for the individual’s cancer risk, clinical management and biological relatives. A positive result does not, however, predict whether or when a person will develop cancer.
A negative result means that no relevant pathogenic variant was identified in the genes included in the test. The meaning of a negative result depends on why testing was performed and whether a specific familial variant was already known. A negative result can be particularly informative when a known familial pathogenic variant has been specifically excluded, while an uninformative negative result may not completely rule out an inherited contribution to cancer risk.
A variant of uncertain significance means that a genetic change has been identified, but there is currently insufficient evidence to determine whether it increases cancer risk. A VUS is generally not considered clinically actionable and should not, on its own, be used to change cancer risk management. The classification may be reviewed in the future as additional evidence becomes available.
In some cases, genetic testing may identify a finding that requires further investigation. For example, a genetic change identified through tumour testing may need germline testing to determine whether it is inherited. This is why the type of test performed and the clinical context are important when interpreting an ovarian cancer genetic test result.
The result should therefore be interpreted alongside the individual’s ovarian cancer diagnosis, personal and family history, the genes included in the test and any relevant tumour findings. Genetic testing does not simply provide a yes-or-no answer about ovarian cancer risk; its clinical meaning depends on the specific genetic finding and the circumstances in which testing was performed.
Single-Gene Testing vs Multigene Panels
Ovarian cancer genetic testing may focus on a single gene or analyse several genes at the same time through a multigene panel. The most appropriate approach depends on the individual’s personal and family history, any known genetic variant in the family, and the clinical features of the cancer.
| Feature | Single-Gene Testing | Multigene Panels |
|---|---|---|
| Testing Approach | Focuses on one specific gene or a known familial genetic variant. | Analyses several genes associated with inherited ovarian cancer risk at the same time. |
| When It May Be Used | Particularly useful when a specific gene is strongly suspected or a pathogenic variant has already been identified in the family. | Useful when several genes could explain the individual’s personal or family history and there is no clear reason to focus on one gene. |
| Scope of Results | Provides focused information about the gene or familial variant being investigated. | Provides broader information and can identify pathogenic variants in genes that may not have been suspected initially. |
| Family Testing | Particularly appropriate for targeted testing when a known familial pathogenic variant has already been identified. | May identify a pathogenic variant that can then be used to offer targeted testing to relevant biological relatives. |
| Interpretation | Results are generally focused on a specific gene or known familial variant. | Broader testing may identify variants of uncertain significance that require careful clinical interpretation. |
What Does a Positive Genetic Test Mean?
A positive ovarian cancer genetic test means that a pathogenic or likely pathogenic genetic variant has been identified in one of the genes analysed. When the finding comes from germline testing, it indicates that the variant is inherited and may be associated with an increased risk of ovarian cancer and, depending on the gene involved, other cancers.
A positive result does not mean that a person has ovarian cancer, or that they will definitely develop cancer in the future. The level of risk depends on the specific gene and variant identified, as well as other factors such as personal and family history. Even people who carry an inherited pathogenic variant may not necessarily develop the associated cancer.
For someone who has already been diagnosed with ovarian cancer, identifying an inherited pathogenic variant may provide additional information about the genetic basis of the cancer and can sometimes help inform treatment decisions. It may also indicate an increased risk of developing certain other cancers in the future.
A positive germline result can also have implications for biological relatives. Because an inherited variant can be passed from a parent to a child, relatives may have a chance of carrying the same variant. Where appropriate, targeted testing for the known familial variant can help determine whether other family members have inherited it.
The meaning of a positive result therefore depends on the specific gene, the type of variant identified and the individual’s clinical circumstances. Genetic counselling can help explain the associated cancer risks and what the result may mean for the individual and their family.
What Does a Negative Genetic Test Mean?
A negative ovarian cancer genetic test means that no pathogenic or likely pathogenic genetic variant was identified in the genes analysed using the available testing methods. However, the meaning of a negative result depends on the reason for testing, the genes included and whether a specific familial variant was already known.
If a known pathogenic variant has already been identified in the family and testing confirms that the individual does not carry that specific variant, this is known as a true negative result. In this situation, the person has not inherited the known familial variant and does not have the increased cancer risk associated with that particular variant. However, a negative result does not mean that the person can never develop ovarian cancer or another type of cancer.
A different situation occurs when there is a strong personal or family history of cancer but no pathogenic variant has been identified in the family. This may be described as an uninformative negative result. It means that no relevant variant was found in the genes tested, but an inherited genetic contribution to cancer risk cannot necessarily be ruled out.
A negative result from germline testing should therefore always be interpreted alongside the individual’s personal and family history. In some circumstances, additional assessment or future genetic testing may be appropriate if new genes, variants or testing methods become available.
A negative genetic test also does not mean that ovarian cancer is absent in someone who has symptoms or has already been diagnosed with the disease. Germline testing assesses inherited genetic risk rather than diagnosing ovarian cancer itself.
The clinical meaning of a negative result therefore depends on the circumstances in which the test was performed. Genetic counselling or specialist clinical assessment can help determine whether the result provides reassurance or whether other risk factors still need to be considered.
Germline Testing vs Tumour Testing
Germline and tumour testing examine genetic changes for different purposes. Germline testing looks for inherited variants that may affect cancer risk, while tumour testing examines genetic changes within cancer cells that may have developed during a person’s lifetime and can sometimes help guide treatment.
| Feature | Germline Testing | Tumour Testing |
|---|---|---|
| What It Examines | Looks for genetic variants that are present in the body’s cells and may have been inherited from a biological parent. | Examines genetic changes found within cancer cells, many of which develop during a person’s lifetime. |
| Sample Used | Usually performed using a blood sample, although saliva or other suitable samples may also be used. | Usually performed using a sample of tumour tissue obtained during diagnosis or surgery. |
| Main Purpose | Assesses inherited cancer susceptibility and can identify variants that may also be relevant to biological relatives. | Identifies genetic changes in the cancer that may provide information relevant to tumour classification or treatment. |
| Implications for Family Members | An inherited pathogenic variant may be relevant to biological relatives, who may be offered targeted testing where appropriate. | A genetic change found only in the tumour is generally acquired and does not indicate that biological relatives have inherited the same variant. |
| Relationship Between the Tests | May be needed to determine whether a genetic finding is inherited when a relevant variant is identified through tumour testing. | A finding that may have a germline origin can require follow-up germline testing to determine whether it is inherited. |
What Happens After Ovarian Cancer Genetic Testing?
After ovarian cancer genetic testing, the result needs to be interpreted in the context of the individual’s personal and family history, the genes analysed and the reason the test was performed. A result may be positive, negative or uncertain, and each type of finding can have different clinical implications.
If a pathogenic or likely pathogenic germline variant is identified, the next step is usually to discuss what that finding means for the individual’s cancer risks and whether any changes to clinical management or further assessment may be appropriate. The specific implications depend on the gene and variant identified.
A positive germline result may also have implications for biological relatives. If an inherited pathogenic variant is identified, appropriate family members may be offered targeted testing to determine whether they carry the same familial variant.
If the result is negative, the level of reassurance depends on the circumstances of testing. A true negative result for a known familial variant can be highly informative, whereas an uninformative negative result may need to be considered alongside the individual’s personal and family history.
A variant of uncertain significance may also be reported. This means that there is currently insufficient evidence to determine whether the genetic change affects cancer risk. Such a finding is generally not used on its own to change clinical management.
Genetic counselling can help explain the result, clarify its implications and determine whether further genetic assessment or testing may be appropriate. For people with ovarian cancer, the interpretation may also need to take into account any relevant tumour testing and the distinction between inherited and acquired genetic changes.
Where an inherited pathogenic variant has been identified, the result may therefore have implications beyond the person who was tested. Appropriate follow-up can help determine what the finding means for the individual and whether genetic testing should be considered for relevant biological relatives.
Frequently Asked Questions About Ovarian Cancer Genetic Testing
What is ovarian cancer genetic testing?
Ovarian cancer genetic testing looks for inherited genetic variants that may increase the risk of ovarian cancer. Testing may analyse one specific gene or several genes through a multigene panel, depending on the individual’s personal and family history and clinical circumstances.
Which genes are commonly tested for ovarian cancer?
Genes commonly included in ovarian cancer germline testing include BRCA1, BRCA2, PALB2, RAD51C, RAD51D, BRIP1 and genes associated with Lynch syndrome, such as MLH1, MSH2 and MSH6. The genes included in a test may vary according to the clinical indication and testing panel.
Does everyone with ovarian cancer need genetic testing?
Genetic testing is considered for people with ovarian cancer when their diagnosis and clinical circumstances meet the relevant testing criteria. In England, current genomic guidance includes germline testing for people with high-grade non-mucinous epithelial ovarian cancer, with additional testing considered when there is a relevant family history.
Is ovarian cancer genetic testing done with a blood test?
Germline testing is usually performed using a blood sample, although other samples such as saliva may also be suitable. Blood testing looks for genetic variants that are present throughout the body’s cells and may have been inherited from a biological parent.
What is the difference between germline and tumour genetic testing?
Germline testing looks for inherited genetic variants that may affect cancer risk, while tumour testing examines genetic changes found in cancer cells. A genetic change found only in a tumour does not usually mean that the same variant has been inherited by biological relatives.
What does a positive ovarian cancer genetic test mean?
A positive result means that a pathogenic or likely pathogenic variant associated with increased cancer risk has been identified. If the variant is found through germline testing, it may indicate an inherited cancer predisposition and can have implications for the individual and relevant biological relatives.
What does a negative ovarian cancer genetic test mean?
A negative result means that no relevant pathogenic variant was identified in the genes analysed. Its significance depends on the reason for testing. If a known familial variant has been specifically excluded, the result can be a true negative; if no familial variant is known, a negative result may not completely exclude an inherited contribution to cancer risk.
Can a genetic test find a variant of uncertain significance?
Yes. Genetic testing can identify a variant of uncertain significance (VUS), meaning that there is currently insufficient evidence to determine whether the variant affects cancer risk. A VUS is generally not considered clinically actionable on its own.
Does a positive ovarian cancer genetic test mean I will develop cancer?
No. An inherited pathogenic variant can increase the risk of developing certain cancers, but it does not mean that cancer will definitely develop. The level of risk depends on the specific gene and variant, as well as other individual factors.
Can ovarian cancer genetic testing affect my family?
Yes. If germline testing identifies an inherited pathogenic variant, biological relatives may have a chance of carrying the same variant. Where appropriate, targeted testing can be offered to relevant family members to determine whether they have inherited the familial variant.
Should I have genetic counselling before or after ovarian cancer genetic testing?
Genetic counselling can help assess whether testing is appropriate, explain the possible results and discuss what the findings could mean for the individual and their family. It can also help interpret results and determine whether further genetic assessment may be appropriate.
