- Hereditary Breast and Ovarian Cancer syndrome (HBOC)
- Lynch syndrome/Hereditary Non-Polyposis Colorectal Cancer (HNPCC)
- Familial Adenomatous Polyposis (FAP)/Attenuated Familial Adenomatous Polyposis (AFAP)
- MUTYH-associated Polyposis syndrome (MAP)
- MUTYH-associated Colon Cancer Risk
- Melanoma Cancer Syndrome (MCS)
- Li-Fraumeni Syndrome (LFS)
- PTEN Hamartoma Tumor syndrome (PHTS)
- Peutz-Jeghers Syndrome
- Hereditary Diffuse Gastric Cancer (HDGC) Syndrome
- Juvenile Polyposis Syndrome (JPS)
- Juvenile Polyposis Syndrome (JPS) and Hereditary Hemorrhagic Telangiectasia (HHT)
- PALB2-associated Cancer Risk
- CHEK2-associated Cancer Risk
- ATM-associated Cancer Risk
- NBN-associated Cancer Risk
- BARD1-associated Cancer Risk
- BRIP1-associated Cancer Risk
- RAD51C-associated Cancer Risk
- RAD51D-associated Cancer Risk
- Polymerase Proofreading-associated Syndrome (PPAS)
- Hereditary Mixed Polyposis Syndrome (HMPS)
Juvenile Polyposis Syndrome (JPS) and Hereditary Hemorrhagic Telangiectasia (HHT) SMAD4 ASSOCIATED CANCER RISKS
Juvenile Polyposis Syndrome (JPS) and Hereditary Hemorrhagic Telangiectasia (HHT)
SMAD4 ASSOCIATED CANCER RISKS
What does it mean to have a diagnosis of Juvenile Polyposis Syndrome and Hereditary Hemorrhagic Telangiectasia?
Juvenile Polyposis Syndrome (JPS) is caused by mutations in one of two genes: BMPR1A and SMAD4. People with JPS have growths in their digestive system that can lead to cancer. These growths are called “juvenile polyps”, and can develop in adults as well as in children. The most common locations for juvenile polyps are the colon, rectum, gastric (stomach) and small intestine. The juvenile polyps can cause problems by bleeding and/or blocking the intestines.
People with JPS have an increased risk for cancers of the colon, rectum, and stomach. There are also slightly elevated risks for small bowel and pancreatic cancers.
People with SMAD4 mutations also have a condition known as Hereditary Hemorrhagic Telangiectasia (HHT). HHT is a condition where people have leaky connections between the arterial and venous parts of their blood system. These are called arteriovenous malformations (AVMs). Small AVMs cause problems when they lead to bleeding in the nose or digestive system, and some people with HHT have frequent nosebleeds or anemia from loss of blood through their intestines. Some individuals with HHT have larger AVMs in their lungs, brain or liver. These can cause serious problems if they are not found and addressed.
What can be done to protect people with JPS and HHT from cancer and other medical problems?
The National Comprehensive Cancer Network (NCCN) provides recommendations for lowering the risk of cancer and other health problems in men and women with JPS. These recommendations include starting screening of the stomach and intestines at young ages and having the screenings frequently. For example, colonoscopies to check for juvenile polyps in the colon should begin at age 15 or younger and should be done every few years. People with JPS should also be checked for anemia, which could be caused by bleeding from juvenile polyps.
There are also detailed recommendations for the care of people with HHT. They include screening for large AVMs in the lungs and brain in order to prevent them from causing serious problems. There are also treatments to reduce nosebleeds in people if the nosebleeds are interfering with their lives or causing anemia.
Both JPS and HHT are relatively rare conditions, so it is recommended that people with JPS be cared for by healthcare professionals with experience in treating these conditions.
Additional details about JPS and HHT, including information about the risks for different kinds of cancer and other medical problems, specific recommendations for medical care, and useful information for relatives of people who have a diagnosis of JPS and HHT, are available within our Support Organizations pages
Associated Syndrome Name: Juvenile Polyposis Syndrome (JPS) and Hereditary Hemorrhagic Telangiectasia (HHT)
SMAD4 Summary Cancer Risk Table
|Cancer||Genetic Cancer Risk|
SMAD4 gene Overview
Juvenile Polyposis Syndrome (JPS) and Hereditary Hemorrhagic Telangiectasia (HHT) 1, 2, 3, 4, 5
- Individuals with SMAD4 mutations have both Juvenile Polyposis Syndrome (JPS) and Hereditary Hemorrhagic Telangiectasia (HHT).
- Patients with JPS have a high risk for cancer as a result of hamartomatous polyps in the gastrointestinal system, particularly in the colon, rectum and stomach. The presence of these polyps is associated with a high risk for colorectal cancer, and can cause bleeding leading to anemia.
- Patients with JPS also have an elevated risk for small bowel and pancreatic cancer.
- This patient also has Hereditary Hemorrhagic Telangiectasia (HHT), which is associated with a high risk for life-threatening arteriovenous malformations of the lungs, brain and liver, as well as nosebleeds.
- Recent studies suggest that patients with SMAD4 mutations have an increased risk for connective tissue disorders such as thoracic aortic disease, brain aneurysm, and lax skin and joints. The data for this are not yet conclusive and there are currently no medical management recommendations associated with connective tissue disorders for carriers of SMAD4 mutations.
- Although there are high risks for cancer in patients with JPS, and high risks for life-threatening complications from the arteriovenous malformations found in patients with HHT, these risks can be greatly reduced with appropriate medical management. Guidelines from the National Comprehensive Cancer Network (NCCN) and the Scientific Advisory Committee of the HHT Foundation are listed below. It is recommended that patients with SMAD4 mutations and diagnoses of JPS and HHT be managed by a multidisciplinary team with experience in the prevention and treatment of the complications associated with these conditions.
SMAD4 gene Cancer Risk Table
|Cancer Type||Age Range||Cancer Risk||Risk for General Population|
|Colorectal||To age 422, 6||20%-25%||<0.2%|
|To age 802, 5, 6||40%-50%||3.0%|
|Gastric||To age 805, 6||Up to 21%||0.6%|
|Pancreatic||To age 802, 5, 6||Rare, but elevated risk||1%|
|Small Bowel||To age 802, 5, 6||Rare, but elevated risk||0.2%|
|Other - Hereditary Hemorrhagic Telangiectasia||All ages3||HHT is associated with a high risk for life threatening arteriovenous malformations of the lungs, brain and liver as well as nosebleeds.||NA|
SMAD4 Cancer Risk Management Table
The overview of medical management options provided is a summary of professional society guidelines as of the last Myriad update shown on this page. The specific reference provided (e.g., NCCN guidelines) should be consulted for more details and up-to-date information before developing a treatment plan for a particular patient.
This overview is provided for informational purposes only and does not constitute a recommendation. While the medical society guidelines summarized herein provide important and useful information, medical management decisions for any particular patient should be made in consultation between that patient and his or her healthcare provider and may differ from society guidelines based on a complete understanding of the patient’s personal medical history, surgeries and other treatments.
|Cancer Type||Procedure||Age to Begin||Frequency |
(Unless otherwise indicated by findings)
|Colorectal||Colonoscopy5, 8, 9||12 to 15 years, or earlier if symptoms are present||Every 2 to 3 years|
|Monitor for rectal bleeding and/or anemia.1, 8||15 years, or earlier if symptoms are present||Annually|
|Colorectal surgical evaluation and counseling.5, 8, 9||Based on cancer diagnosis and/or polyp number, size and histology||NA|
|Gastric||Upper endoscopy5, 7||15 years||Every 2 to 3 years|
|Pancreatic||Currently there are no specific medical management guidelines for pancreatic cancer risk in mutation carriers.||NA||NA|
|Small Bowel||Capsule endoscopy8||15 years, or earlier if symptoms are present||Individualized|
|Other - Hereditary Hemorrhagic Telangiectasia||Multiple screenings recommended, which may include brain MRI, contrast echocardiogram, and chest CT.3||Some screenings are recommended within the first 6 months of life||Varies|
Information for Family Members
The following information for Family Members will appear as part of the MMT for a patient found to have a mutation in the SMAD4 gene.
A major potential benefit of myRisk genetic testing for hereditary cancer risk is the opportunity to prevent cancer in relatives of patients in whom clinically significant mutations are identified. Healthcare providers have an important role in making sure that patients with clinically significant mutations are informed about the risks to relatives, and ways in which genetic testing can guide lifesaving interventions.
Since SMAD4 mutations carry a risk for complications in children and some screenings are recommended to begin in infancy, mutation testing should occur within the first 6 months after birth.5
- Larsen Haidle J, Howe JR. Juvenile Polyposis Syndrome. 2017 Mar 9. In: Pagon RA, et al., editors. GeneReviews® [Internet]. Available from http://www.ncbi.nlm.nih.gov/books/NBK1469/ PMID: 20301642.
- Howe JR, et al. The risk of gastrointestinal carcinoma in familial juvenile polyposis. Ann Surg Oncol. 1998 5:751-6. PMID: 9869523.
- Faughnan ME, et al. HHT Foundation International - Guidelines Working Group. International guidelines for the diagnosis and management of hereditary haemorrhagic telangiectasia. J Med Genet. 2011 48:73-87. PMID: 19553198.
- O'Malley M, et al. The prevalence of hereditary hemorrhagic telangiectasia in juvenile polyposis syndrome. Dis Colon Rectum. 2012 55:886-892. PMID: 22810475.
- Provenzale D, et al. NCCN Clinical Practice Guidelines in Oncology® Genetic/Familial High-Risk Assessment: Colorectal. V 1.2018. July 12. Available at http://www.nccn.org.
- Fast Stats: An interactive tool for access to SEER cancer statistics. Surveillance Research Program, National Cancer Institute. https://seer.cancer.gov/faststats. (Accessed on 1-2-2017)
- Ajani JA, et al. NCCN Clinical Practice Guidelines in Oncology®: Gastric Cancer. V 2.2018. May 22. Available at http://www.nccn.org.
- Achatz MI, et al. Cancer Screening Recommendations and Clinical Management of Inherited Gastrointestinal Cancer Syndromes in Childhood. Clin Cancer Res. 2017 23:e107-e114. PMID: 28674119.
- Syngal S, et al. ACG clinical guideline: Genetic testing and management of hereditary gastrointestinal cancer syndromes. Am J Gastroenterol. 2015 110:223-62. PMID: 25645574.
Last Updated on 09-Jul-2019