PUBLISHED: 17th July 2025
The SMAD4 gene is a tumor suppressor. It transmits signals from the cell surface to the nucleus. The signals keep cells from growing and dividing too fast or in an uncontrolled way.
What is an SMAD4 mutation?
People with a mutation in an SMAD4 gene have a condition called Juvenile Polyposis syndrome (JPS). JPS increases the risk for polyps (growths of tissue) in the colon or rectum. These polyps can lead to an increased risk of colorectal cancer. JPS also increases the risk of stomach cancer.
What are the risks of cancer for people with SMAD4 mutation?
Having a mutation in an SMAD4 gene increases the risk of developing colon and stomach cancer, especially if you have polyps in your stomach.
| Cancer type | Lifetime risk with a SMAD4 mutation | Lifetime risk for the general population |
| Colon cancer | Up to 50% | 4% |
| Stomach cancer | Up to 21%, especially if you have polyps in your stomach | Less than 1% |
JPS may also increase the risks of small intestine and pancreatic cancers, but these are much less common.
What can people with an SMAD4 mutation do?
Expert guidelines provide recommendations for screening for colorectal and stomach cancer in people with an SMAD4 mutation.
People with an inherited SMAD4 mutation may qualify for specific treatments or clinical trials.
Cancer risk management for people with an SMAD4 mutation
If you have an SMAD4 mutation, we recommend that you speak with a genetics expert who can look at your personal and family history of cancer and help you decide on a plan for managing your risk.
Expert guidelines are available to help people with an SMAD4 mutation manage their increased cancer risk.
National Comprehensive Cancer Network guidelines for people with an SMAD4 mutation
Colorectal and stomach cancer risk management
| Cancer type | Beginning age | Recommendation | Additional Information |
| Colon cancer | ~18 | Colonoscopy every 1-3 years. Time between colonoscopies should be based on number, size and pathology of polyps. | Based on NCCN guidelines |
| Stomach cancer | ~18 | Upper endoscopy (a procedure that lets your doctor see inside your stomach and small intestine) every 1–3 years. Time between upper endoscopies should be based on number, size and pathology of polyps. | Based on NCCN guidelines |
There are no screening guidelines for other types of cancer in people with an SMAD4 mutation.
Cancer treatment
There are no specific treatment considerations for people with an SMAD4 mutation.
If you have an SMAD4 mutation, you should try to find a team of doctors who have experience in genetics and hereditary gastrointestinal cancer syndromes.
Other considerations
People with an SMAD4 mutation are at increased risk for hereditary hemorrhagic telangiectasia or HHT. The lifetime risk of HHT for people with an SMAD4 mutation is about 22%.
HHT is characterized by the presence of deformities in the body's network of blood vessels, including arteries, veins and capillaries. These can result in chronic bleeding and acute hemorrhage.
If a family has a known SMAD4 mutation, genetic testing should be done on an infant within the first 6 months of life due to the risk of HHT.
Ask your doctor
If you or a family member has a mutation in SMAD4, consider asking your doctor the following:
- What symptoms should I watch for?
- Are there new options for cancer prevention, treatment or clinical trials I should know about?
As we learn more about SMAD4 mutations, we may also learn more about the risk of other cancers. It is important to check in with a genetics expert to ensure you receive the most up-to-date information about cancer risks and medical options for people with an SMAD4 mutation.