Genetic Testing for Diffuse Stomach Cancer

What is inherited stomach cancer?

Stomach cancer is also called gastric cancer. It is a cancer that has started anywhere in the stomach or the stomach wall. Stomach cancer is relatively uncommon in the UK, although it is much more common in other parts of the world.

Only a small proportion of people with stomach cancer have an inherited tendency to develop this cancer.

You have been given this leaflet because the type of stomach cancer you have been diagnosed with is the diffuse type. This can sometimes be due to an inherited condition called CDH1-related cancer syndrome.

What is CDH1-related cancer syndrome?

This is an inherited condition caused by a change in a gene called CDH1. CDH1 gene changes cause people to have a higher chance of developing diffuse stomach cancer, usually at a younger age than people typically develop these cancers.

Not everyone who has a change in the CDH1 gene will develop cancer. Over a person’s lifetime:

For men:

• Up to 7 in 10 men with the CDH1 gene change will develop stomach cancer.
• Men with the CDH1 gene change may have slightly increased risk of male breast cancer, but most men will not develop breast cancer.

For women:

• Up to 6 in 10 women with the CDH1 gene change will develop stomach cancer.
• Up to 6 in 10 women with the CDH1 gene change will develop breast cancer.

The above figures are averages and individual risk could vary depending on family history.

What are genes?

Genes are messages which instruct cells how to grow and function. Genes come in pairs; we inherit one copy from each parent.

Who can have CDH1 genetic testing?

CDH1 testing is offered to people with diffuse stomach cancer diagnosed at a younger age or in people who have a relevant family history.

What happens when I get tested for CDH1-related cancer syndrome?

A blood sample is taken and sent to the genetics laboratory. They look for mutations (changes) in the CDH1 gene. Results typically take less than 6 months following sample collection. If you haven’t received your result within 6 months, please raise this with the gastric cancer specialist nurses.

What should I consider before having testing?

• The blood sample is only tested for CDH1 gene changes. You will not find out about the risk of any other genetic conditions.
• It is standard practice for the hospital to store the sample for many years in case there is a need to do future tests.
• Stored samples may be used for quality checks and the development of new tests.
• The result may be very important for your relatives. It is often helpful to discuss genetic testing with close family members before you have the results.
• The test result will be given to you initially, but information may then be shared to help your family members.

What are the possible results of genetic testing?

Testing can reveal one of three results:

1. No gene changes are found

This means it is unlikely that the cancer is caused by a CDH1-related cancer syndrome. However, there may still be other genes that can cause stomach cancer which we are not yet able to offer testing for or that we do not know about. Family members may still have an increased risk compared to the general population. Relatives will not be offered a genetic test but they may be offered additional screening.

2. A cancer-causing gene is found

This confirms that your cancer was caused by an inherited tendency to develop this cancer. Relatives can have a test if they want to know whether they have inherited the same gene change. This is generally only offered to adults over 18 years.

3. A variant of uncertain significance is found

This is a gene change of unknown significance which may be entirely harmless. Relatives will not be offered a genetic test but they may be offered additional screening if they meet specific criteria. Sometimes research into the significance of the variant may be possible and will be discussed if appropriate. You and your family may be advised to be referred to the Genetics team in 3 to 5 years to review this result.

What will happen if I have a CDH1 gene change?

If you have stomach cancer, and if the cancer is confined to the stomach, you will be offered surgery to remove your stomach. This will hopefully treat the diagnosed stomach cancer but will also stop you from developing a new stomach cancer in the future.

If you are female, you are at a higher risk of developing breast cancer. You will be referred for extra breast cancer screening and will be offered annual breast MRI and/or mammograms from the age of 30 years. You may be offered a referral to a breast surgeon to discuss your breast cancer risk and options available to try to reduce this risk.

If you are male, you may have a slightly increased risk of developing breast cancer compared with men without this gene change, but the risk is still very low. There is no screening for male breast cancer at this level of risk. Men should be “chest aware” and see their GP with any concerns. Please see the CoppaFeel website for further advice about this.

You will be offered a referral to the Genetics team to discuss your result. Your close relatives (adults) will be advised to seek a referral to their local Genetics team too. If any of your relatives are also found to have the CDH1 gene change, they will be referred to meet a stomach surgeon to discuss treatment options. If female, they will be referred to the high-risk breast cancer screening programme.

Implications for Family Members

If you are found to have a cancer-causing gene change, there is a risk of this being passed onto family members. This will be discussed in more detail during your consultation with your treating consultant. The clinical genetics team can help to determine which family members will be eligible for CDH1 gene testing.

Current Research

Current research in the UK is led by Cambridge University Hospital. The Familial Gastric Cancer study was set up in 1997 to collect information and blood samples from families with multiple cases of gastric cancer. They are recruiting patients with diffuse gastric cancer to this study. If you are interested in finding out more about this study and whether you would be eligible, please speak with your treating consultant.

For more information:

If you need more information, please seek a referral to your local Genetics Department.

Other sources of information: