What Is Colorectal Cancer Testing?
Colorectal cancer testing can refer to several different types of medical assessment used to detect colorectal cancer, investigate suspicious findings, or identify an inherited genetic predisposition to the disease. In this article, the focus is specifically on genetic testing for colorectal cancer and how it can help identify inherited genetic variants associated with an increased risk of developing colorectal cancer.
Genetic testing examines a person’s DNA for specific inherited changes that may increase susceptibility to colorectal cancer and other related conditions. Depending on the clinical circumstances, testing may involve a single gene or a multigene panel that examines several genes associated with hereditary colorectal cancer.
This is different from routine colorectal cancer screening. Screening methods are designed to detect signs of colorectal cancer or precancerous changes, while genetic testing looks for inherited changes in DNA that may help explain why a person or family has an increased risk.
Genetic testing may be considered when there are particular features in a person’s personal or family medical history, a known genetic variant in the family, or other clinical findings that suggest an inherited predisposition. The appropriate test is therefore determined according to the individual’s circumstances rather than being the same for everyone.
Understanding the purpose of colorectal cancer testing is important because a genetic test does not diagnose colorectal cancer itself. Instead, it can provide information about whether an inherited genetic factor may contribute to a person’s risk and whether this information could also be relevant to biological relatives.
For a broader explanation of genetic testing, including the different types of genetic tests and how they are performed, see our Genetic Testing guide.
When Is Genetic Testing Considered for Colorectal Cancer?
Genetic testing for colorectal cancer is not routinely required for everyone. It is generally considered when a person’s personal or family history, clinical findings, or previous genetic results suggest that an inherited genetic variant may be contributing to colorectal cancer risk. The decision to test is based on the overall clinical picture rather than on a single factor.
The decision to proceed with colorectal cancer genetic testing depends on the individual’s clinical and family history rather than on colorectal cancer diagnosis alone. When specific features raise the possibility of an inherited predisposition, genetic testing can help clarify whether an inherited variant is present and whether the finding may also be relevant to biological relatives.
Germline Genetic Testing for Colorectal Cancer
Germline genetic testing for colorectal cancer looks for inherited genetic variants that are present in the DNA of cells throughout the body. Unlike changes that develop only within a tumour, germline variants are inherited from a biological parent and may also be relevant to other family members.
For colorectal cancer, germline testing is usually performed using a blood or saliva sample. The laboratory analyses specific genes associated with inherited cancer susceptibility to identify pathogenic variants or other genetic changes that may increase the risk of colorectal cancer.
The choice of genes tested depends on the individual’s personal and family history, clinical findings and any previous tumour testing. Testing may focus on a specific gene when there is a known familial variant or a strong clinical indication, while multigene panel testing may be considered when several inherited conditions could explain the clinical picture.
Germline testing can be particularly important when colorectal cancer occurs at a younger age, when there are multiple relevant cancers or polyps, or when tumour findings raise the possibility of an inherited predisposition. In some cases, testing can also identify an inherited variant that may have implications for biological relatives.
It is important to distinguish germline genetic testing from tumour testing. Tumour testing examines genetic or molecular changes within cancer cells, while germline testing looks for inherited variants that are present throughout the body. The two approaches can sometimes be used together to investigate whether a tumour finding may have an inherited genetic explanation.
The results of germline testing can provide important information about inherited colorectal cancer risk, but a negative result does not necessarily mean that no genetic contribution exists. Not every possible genetic cause can be identified by current testing, and some results may require further clinical interpretation.
Which Genes Are Tested for Colorectal Cancer?
Colorectal cancer genetic testing may examine several genes associated with inherited cancer susceptibility. The genes included in a test depend on the individual’s personal and family history, clinical findings and, where relevant, previous tumour results. A multigene panel may be used when more than one inherited condition could explain the clinical picture.
| Gene | Main Association | Why It May Be Tested |
|---|---|---|
| MLH1 | Lynch syndrome | May be investigated when clinical or tumour findings suggest an inherited mismatch repair condition. |
| MSH2 | Lynch syndrome | Testing may help identify an inherited mismatch repair variant associated with increased colorectal cancer risk. |
| MSH6 | Lynch syndrome | May be included when the clinical or family history indicates possible Lynch syndrome. |
| PMS2 | Lynch syndrome | May be tested as part of a mismatch repair gene panel for suspected inherited colorectal cancer risk. |
| EPCAM | Lynch syndrome | Certain EPCAM alterations can affect MSH2 function and may therefore be included in Lynch syndrome testing. |
| APC | Familial adenomatous polyposis | May be tested when the number or pattern of colorectal polyps raises the possibility of an inherited polyposis condition. |
| MUTYH | MUTYH-associated polyposis | May be included when colorectal polyposis or other clinical features suggest a possible inherited MUTYH-related condition. |
| Other colorectal cancer susceptibility genes | Several rarer inherited conditions | Broader multigene panels may include additional genes when the clinical history cannot be explained by testing a single gene or a limited group of genes. |
There is no single genetic test that is appropriate for every person with colorectal cancer. The genes examined as part of colorectal cancer testing are selected according to the individual’s clinical circumstances, and multigene panels can allow several relevant inherited conditions to be assessed at the same time.
Single-Gene Testing vs Multigene Panels
Single-gene testing examines one specific gene for inherited variants associated with colorectal cancer. It may be appropriate when a particular genetic condition is strongly suspected or when a pathogenic variant has already been identified in a biological relative. In these situations, testing can be directed towards the relevant gene rather than analysing a broader group of genes.
For example, if a known familial pathogenic variant has previously been identified, testing another family member for that specific variant may provide a clear and targeted result. This approach can also be useful when a person’s clinical features strongly point towards a particular inherited condition.
Multigene panel testing examines several genes at the same time. It may be considered when the clinical presentation could be explained by more than one hereditary condition, particularly because different colorectal cancer syndromes can have overlapping features. Panels may include genes associated with Lynch syndrome, inherited polyposis conditions and other colorectal cancer susceptibility syndromes.
One advantage of a multigene panel is that it can identify a pathogenic variant in a gene that was not initially suspected. This can be particularly relevant when the personal or family history does not clearly point towards one specific syndrome. Current clinical guidance supports considering multigene panel testing when more than one gene may be relevant to the patient’s history.
However, broader testing does not necessarily mean a clearer result. Multigene panels can identify variants of uncertain significance (VUS), meaning that the clinical importance of the genetic change is not currently known. These findings generally require careful interpretation and should not automatically be treated as evidence of increased cancer risk.
The choice between single-gene testing and a multigene panel is therefore based on the individual’s clinical circumstances. The aim of colorectal cancer testing is not simply to analyse as many genes as possible, but to select an appropriate testing strategy that can provide clinically meaningful information.
Germline Testing vs Tumour Testing
Germline and tumour testing examine genetic information for different purposes. Understanding the distinction is important when considering colorectal cancer testing, particularly when a tumour result raises the possibility of an inherited genetic condition.
| Feature | Germline Testing | Tumour Testing |
|---|---|---|
| What Is Examined? | Looks for inherited genetic variants that are present throughout the body’s cells. | Looks for genetic and molecular changes that have developed within cancer cells. |
| Typical Sample | Usually a blood or saliva sample containing DNA that reflects inherited genetic information. | Usually a sample of tumour tissue, although some tumour profiling approaches may use other samples. |
| Main Purpose | To determine whether a person carries an inherited variant that may increase cancer risk. | To identify molecular features of a cancer that may help with diagnosis, classification or treatment decisions. |
| Family Implications | A pathogenic inherited variant may also be relevant to biological relatives and can allow targeted family testing. | A tumour variant usually reflects changes acquired by the cancer and does not, by itself, establish that the change is inherited. |
| Role in Colorectal Cancer Testing | Can confirm whether a suspected inherited predisposition is present. | Can identify tumour features that may indicate the need for further germline investigation. |
Germline and tumour testing answer different clinical questions. A tumour test may identify a genetic change within colorectal cancer cells, but further germline testing may be needed to determine whether a relevant variant is inherited. Conversely, someone who meets criteria for germline testing should not necessarily be excluded from testing simply because tumour testing does not identify an inherited cause.
What Can Colorectal Cancer Genetic Testing Results Show?
Colorectal cancer genetic testing can produce several different types of results, and each result has a different clinical meaning. A report may identify a pathogenic or likely pathogenic variant, find no relevant genetic change in the genes tested, or identify a variant of uncertain significance (VUS).
A pathogenic or likely pathogenic variant means that a genetic change associated with an increased risk of colorectal cancer has been identified. When such a variant is found through germline testing, it may provide evidence of an inherited predisposition and can also have implications for biological relatives who may carry the same variant.
A negative result means that no relevant pathogenic variant was identified in the genes included in the test. However, the significance of a negative result depends on the circumstances in which testing was performed. A negative result is particularly informative when a specific pathogenic variant is already known in the family.
Genetic testing can also identify a variant of uncertain significance. This means that a genetic change has been detected, but there is currently insufficient evidence to determine whether it is associated with an increased risk of colorectal cancer. A VUS should not normally be used on its own to make clinical management decisions and may be reclassified as more evidence becomes available.
In some circumstances, genetic testing may also identify a finding that is unrelated to the reason the test was originally requested. Such findings are generally considered in the context of the testing strategy and the individual’s clinical circumstances.
The result therefore needs to be interpreted alongside the person’s personal and family history, the genes included in the test and, where relevant, previous tumour findings. Genetic testing does not simply produce a straightforward yes-or-no answer about colorectal cancer risk; the clinical context is essential for understanding what a particular result means.
What Does a Negative Genetic Test Mean?
A negative result from colorectal cancer testing means that no pathogenic or likely pathogenic genetic variant was identified in the genes examined. However, the meaning of a negative result depends on why the test was performed, what genes were analysed, and whether a specific genetic variant was already known in the family.
A negative result from colorectal cancer testing should be interpreted according to the individual’s clinical and family history and the scope of the test performed. A negative result can be highly informative when a known familial variant has been excluded, but when no familial variant is known, it may not completely rule out an inherited contribution to colorectal cancer risk.
What Happens After Colorectal Cancer Genetic Testing?
After colorectal cancer genetic testing, the next steps depend on the result, the reason testing was performed, and the individual’s personal and family history. A genetic result should not usually be considered in isolation, as its significance may affect future risk assessment, screening decisions and, in some cases, other biological relatives.
If a pathogenic or likely pathogenic variant is identified, further clinical assessment may be recommended. The specific follow-up depends on the gene involved and the associated cancer risks. This may include a personalised screening plan or referral to appropriate specialists for further management.
A confirmed inherited variant can also have implications for biological relatives. Where appropriate, family members may be offered targeted testing for the specific familial variant rather than undergoing a broad genetic panel. This can help determine which relatives have inherited the same genetic change.
If the result is negative, the appropriate follow-up depends on whether a known familial variant was being tested. A true negative result may provide reassurance when a specific pathogenic variant has already been identified in the family. However, an uninformative negative result may still require consideration of the individual’s personal and family history when determining future care.
If a variant of uncertain significance is identified, it generally should not be used on its own to make changes to cancer management. Further evidence may become available over time and can sometimes lead to the variant being reclassified.
Genetic counselling can be an important part of the process after testing. A genetics-trained healthcare professional can help explain the result, discuss its implications for the individual and family, and clarify whether further testing or clinical assessment may be appropriate.
For individuals with a positive inherited finding, the information may also be relevant to relatives who could carry the same variant. In this situation, discussing the result with a specialist can help determine whether targeted family testing should be considered.
The next step after colorectal cancer testing is therefore not necessarily another genetic test. The result needs to be interpreted in its clinical context so that any appropriate follow-up, screening or family assessment can be considered.
Frequently Asked Questions About Colorectal Cancer Testing
What is colorectal cancer genetic testing?
Colorectal cancer genetic testing looks for inherited genetic variants that may increase a person’s risk of developing colorectal cancer. Testing may examine a single gene or several genes using a multigene panel, depending on the individual’s personal and family history and other clinical findings.
Who should consider genetic testing for colorectal cancer?
Genetic testing may be considered when colorectal cancer occurs at a younger age, when there are multiple relevant cancers or polyps, when a hereditary cancer condition is suspected, or when a known pathogenic variant has been identified in the family. The decision to test is based on the individual’s clinical circumstances rather than a single factor.
What genes are tested for colorectal cancer?
The genes tested depend on the suspected inherited condition and the individual’s clinical history. Testing may include genes such as MLH1, MSH2, MSH6, PMS2, EPCAM, APC and MUTYH, as well as other genes associated with colorectal cancer susceptibility.
Is colorectal cancer genetic testing the same as tumour testing?
No. Germline genetic testing looks for inherited variants that are present throughout the body’s cells, usually using a blood or saliva sample. Tumour testing examines genetic or molecular changes within cancer cells. The two types of testing answer different clinical questions and may sometimes be used together.
What does a positive colorectal cancer genetic test mean?
A positive result means that a pathogenic or likely pathogenic genetic variant associated with increased cancer risk has been identified. Depending on the gene involved, the result may provide information about inherited colorectal cancer risk and may also have implications for biological relatives.
What does a negative colorectal cancer genetic test mean?
A negative result means that no relevant pathogenic variant was identified in the genes included in the test. Its significance depends on the reason for testing. If a known familial variant was specifically tested and not found, this may be considered a true negative result. If no familial variant has been identified, a negative result may not completely exclude an inherited contribution to cancer risk.
What is a variant of uncertain significance (VUS)?
A variant of uncertain significance is a genetic change for which there is currently insufficient evidence to determine whether it affects cancer risk. A VUS should not usually be used on its own to guide clinical management, and its classification may change as further evidence becomes available.
Can colorectal cancer genetic testing be done with a blood or saliva sample?
Yes. Germline genetic testing is commonly performed using a blood or saliva sample. The sample is analysed in a genetic testing laboratory for relevant inherited genetic variants.
Can genetic testing for colorectal cancer help family members?
Yes. If a pathogenic inherited variant is identified, biological relatives may have an increased chance of carrying the same variant. Where appropriate, relatives may be offered targeted testing for the known familial variant rather than undergoing a broad genetic panel.
What happens after colorectal cancer genetic testing?
The next steps depend on the test result and the individual’s clinical circumstances. A pathogenic variant may lead to further clinical assessment and personalised management, while a negative or uncertain result may require interpretation alongside personal and family history. Genetic counselling may also help explain the result and its implications for the individual and their relatives.
Can a negative genetic test rule out hereditary colorectal cancer?
No, not in every situation. A negative result can be highly informative when a known familial pathogenic variant has been specifically excluded, but an uninformative negative result does not necessarily rule out an inherited predisposition. This may be because the relevant genetic cause has not been identified or was not included or detectable in the original test.
Can colorectal cancer genetic testing be repeated?
Usually, the same genetic test does not need to be repeated because a person’s inherited genetic information does not normally change. However, additional or updated testing may sometimes be appropriate if new genes become clinically relevant, testing technology improves, or new clinical information changes the assessment.
