Summary

• A group of cancers including bowel cancer (known as colorectal cancer) and endometrial cancer (cancer of the lining of the uterus or womb), as well as some other cancers are known to be associated with certain inherited gene changes.
• This test looks for inherited genetic changes that would increase someone’s risk of developing these cancers. If someone one has an increased risk for these cancers, there are things they can do to reduce the chance of developing cancer or detect cancer early when treatment outcomes are better.
• It should be noted that most cases of bowel and endometrial cancers are not caused by an inherited cancer syndrome.
• Inherited gene changes and the link with bowel and endometrial cancers

Genes and cancer

Many different inherited genetic changes, also known as mutations, are known to increase the chance of developing bowel, endometrial and other cancers.

Genes are the instructions that tell our body how to function. They are contained within our DNA. We get half our genes from our mother and half from our father, and this genetic makeup does not change throughout our life.  

Some of these genes work to help prevent us from developing cancer. Different genes help to prevent different types of cancer and may help to prevent one or many different cancer types. They are not perfect at preventing cancer which is why some people do develop cancer. Also, they work less well as we age, which is why older people are at an increased risk of cancer. 

Some people are born with a mutation or fault, which is called a germline mutation, in one or more of these cancer-preventing genes. This is usually inherited from a parent. This fault means a person only has one working copy of that particular cancer-preventing gene instead of two, making them more likely to develop the cancer type(s) usually prevented by that gene. Some genes that are more commonly found to have germline mutations and the associated cancer risks are listed in the table.

How cancer occurs

Our cells have a lifespan – they get old and die off. Before they die, they make new copies of themselves, and this can lead to copying mistakes being made.

Normally, our bodies get rid of these mistakes or else repair them but sometimes this does not happen. These mistakes can lead to these cells growing too fast and into places they should not be growing. This is what causes cancer and there are different ways it can happen.

Certain genes make cells grow or divide, others slow down cell division or trigger cells to die at the right time.  Cancers are often caused by changes to the genes that control these processes.  This can cause cells to grow rapidly in an uncontrolled way.
 

The genes that are affected in people who have Lynch syndrome, familial adenomatous polyposis, and the other conditions in the table above are different. They occur because the repair system does not work. The genes associated with these conditions repair the copying mistakes that can occur when a cell is making a new copy of itself. A mutation in these genes means that this repari system does not work. They are called mismatch-repair (MMR) genes.

If these MMR genes are mutated and not working properly, cancer cells grow rapidly in an uncontrolled way.  If you inherit a genetic mutation in one of your MMR genes it can increase your chance of developing cancer throughout your lifetime. If you have a cancer, the cancer cells may be tested for mutations in these genes that have occurred only in these cells. This type of mutation is called a somatic mutation. You can find more information about this here: somatic tumour gene testing.

Why get tested?

If you have bowel or endometrial cancer and you have a family history of these cancers or a related cancer, you may be offered genetic testing. This would usually mean that you have multiple family members with bowel or endometrial cancer, or family members who have been diagnosed with cancer at a young age, usually before age 50. Testing may find the genetic mutation responsible for the cancers in your family.

Genetic testing of an unaffected person is generally not performed unless a specific genetic mutation – a pathogenic variant – has already been identified in a family member. An affected family member, someone who has had cancer, will need genetic testing first to identify if there is a genetic mutation responsible for their cancer and the cancer in other family members. A genetic service will help you identify the most appropriate family member for testing. If no one in the family who has had cancer can be tested, you should still speak with a genetic service as they may be able to find alternative options for testing or advise you on your cancer risk just based on the family history.

Once an inherited mutation has been identified, other family members who do not have cancer can then be tested to assess their personal cancer risk. This is known as predictive or pre-symptomatic testing. Predictive or pre-symptomatic testing is helpful in deciding whether to take additional measures such as regular surveillance through screening or prophylactic surgery (surgery done before cancer develops) that may reduce the chance of developing certain cancers in the future.

Genetic testing of unaffected family members is most commonly offered through a family cancer clinic. If a person is referred to a family cancer clinic, the potential benefits, limitations, and possible consequences of genetic testing will be discussed before deciding whether to proceed. This testing can also be arranged through private genetic testing services.  However, you may have to pay for testing and the quality of service and testing is not guaranteed. 

Having the test

Sample 

Blood.

Preparation

None.

Your results

Positive result

If there is a positive result and a genetic mutation is detected, a genetic counsellor will explain the meaning of the result and tell you about the risk of cancer. They will explain the steps that can be taken which may include regular screening, prophylactic surgery or risk-reducing medication.  Risk-reducing interventions are different depending on the cancer type(s) and your personal situation.  

Having a cancer-causing gene mutation does not necessarily mean you will develop cancer. Some people with disease-causing mutations in a gene develop cancer, while others with the same mutations do not. This is known as incomplete penetrance.  Incomplete penetrance is not fully understood but probably due to a combination of genetic, environmental and lifestyle factors.

A genetic counsellor will talk about the chance of other people in your family having the genetic mutation. They will give you advice on how to inform family members that they are at risk of having the genetic mutation and how they can have testing. If you do not want or cannot have these conversations with your family, the genetic service may be able to inform family members on your behalf in a way that does not reveal that you have the genetic mutation. This is important so that these family members can find out if they are at an increased risk of developing cancer and take steps to reduce this risk or detect cancer early.  

Negative result

If you are having a test for a genetic mutation because it has been found in a relative, a negative result means you do not have the genetic mutation. This means you are not at an increased risk of developing cancer based on your genetic result. You will still be at the same risk as the general population and as with everyone, you should still see your doctor if you develop concerning symptoms.

This result also means that any children you have will not have the genetic mutation and will not need to have their own genetic test. Your result does not change the chance of your siblings having or not have the genetic mutation.

If you have had bowel or endometrial cancer and you are having tests for the genetic mutations responsible, a negative result may also mean that you have a genetic variant which is not detectable by the particular test method being used or that you have a variant in a different, perhaps undiscovered, gene. You may be offered to be re-tested in 5-10 years when more information is available.

If you have had bowel or endometrial cancer and you are having tests for a genetic mutation, there are two other possible results:

Variant of uncertain significance (VUS)

There is a small chance that genetic testing may find a genetic mutation for which it is not yet known whether it increases a person’s risk of cancer. This is known as a Variant of Uncertain Significance or VUS. If a VUS is found, a genetic counsellor or specialist will explain what it means. In some circumstances, it may help to test other family members for the VUS. As there is not enough information about the effects of the VUS, you may also be asked to return for further testing in 5-10 years when more information is available.

Incidental finding

Very rarely, a genetic mutation which increases your risk of developing other cancer types or other, unrelated conditions (such as heart conditions) is found. The chance of this happening varies between tests and will be discussed with you before you have testing. If this happens, a genetic counsellor or specialist will discuss what this result means for you and your family. 

More to know?

Someone is said to have Lynch Syndrome when they have a mutation in any one of MLH1, PMS2, MSH2 or MSH6. Each of these genes increases the risk of different cancer types and by different amounts.

Questions to ask your doctor

The choice of tests your doctor makes will be based on your medical history and symptoms. It is important that you tell them everything you think might help. 

You play a central role in making sure your test results are accurate. Do everything you can to make sure the information you provide is correct and follow instructions closely. 

Talk to your doctor about any medications you are taking. Find out if you need to fast or stop any particular foods or supplements. These may affect your results. Ask:

• Why does this test need to be done?
• Do I need to prepare (such as fast or avoid medications) for the sample collection?
• Will an abnormal result mean I need further tests?
• How could it change the course of my care?
• What will happen next, after the test?

More information

Pathology and diagnostic imaging reports can be added to your My Health Record.

You and your healthcare provider can now access your results whenever and wherever needed. Get further trustworthy health information and advice from healthdirect.