SMAD4 gene testing and cancer
SMAD4 gene testing is a genetic analysis aimed at identifying mutations in the SMAD4 gene, which plays a crucial role in regulating normal cell growth. Mutations in this gene are associated with several cancers, particularly those of the gastrointestinal tract and pancreas, and are a contributing factor to juvenile polyposis syndrome (JPS), a hereditary condition that increases the risk of colorectal cancer. Genetic testing is particularly beneficial for individuals exhibiting symptoms of JPS and for their relatives, allowing for early detection and preventative measures. Testing typically involves a blood sample or cheek cells, with results guiding further clinical management and surveillance strategies, such as regular colonoscopies starting at age fifteen.
As advancements in sequencing technology continue to improve detection rates, understanding SMAD4 mutations may also provide insights into targeted therapies for affected patients. While the procedure is generally safe, potential psychological impacts from the results underscore the need for genetic counseling before and after testing. Identifying specific mutations can facilitate family screening and help in making informed health decisions regarding cancer risk and management.
On this Page
Subject Terms
SMAD4 gene testing and cancer
ALSO KNOWN AS: DPC4, MADH4
DEFINITION: The SMAD4 gene product maintains normal cell growth rates. Mutations in SMAD4 lead to uncontrolled cell growth and, ultimately, to many cancers, especially those of the gastrointestinal tract and pancreas. Inherited mutations in SMAD4 are one cause of juvenile polyposis syndrome (JPS), an inherited condition that results in a predisposition to colorectal cancer.
Cancers diagnosed: Juvenile polyposis syndrome, familial colon cancer, pancreatic cancer, colorectal cancer, lung cancer, kidney cancer, esophageal cancer, and biliary tract cancer
Why performed: Between 20 and 60 percent of individuals afflicted with JPS, a condition where numerous polyps form in the colon, bear mutations in the SMAD4 gene. Other cases may be caused by mutations in BMPR1A or other genes. Although polyps resulting from JPS are initially benign, a small proportion may develop into carcinomas. Genetic testing is performed to confirm a diagnosis of patients exhibiting symptoms of JPS and to characterize the SMAD4 mutation causing the disease. Because JPS is an inherited disorder, genetic testing is also often done in previously undiagnosed relatives of JPS patients to determine whether prophylactic treatment is required. Testing is performed at or before age fifteen, when routine screening by colonoscopy is recommended.
Patient preparation: Patients considering genetic testing may meet with a genetic counselor to discuss the benefits and risks of the test and the significance of negative, positive, and inconclusive tests. Material required for genetic testing is obtained from a blood sample or cheek cells obtained by mouthwash. No special preparation is required.
Steps of the procedure: Samples are sent to a clinical laboratory that offers SMAD4 screening. Deoxyribonucleic acid (DNA) is isolated from the blood sample, and the DNA that encodes SMAD4 is amplified by polymerase chain reaction (PCR) and sequenced using standard methods.
After the procedure: The patient will consult with a physician and genetic counselor to discuss the implications of the test results.
In the twenty-first century, improved detection methods have enhanced doctors' ability to detect SMAD4 gene mutations through advances in sequencing technologies. Identifying SMAD4 mutations has also proven to be an accurate biomarker for what treatments may be successful for patients. Research continues to find implications of SMAD4 mutations in targeted therapies and immunotherapies. Finally, researchers continue to study SMAD4 mutations and their indication of an increased chance of metastasis in certain cancer patients.
Risks: Complications from drawing blood are rare but may include excessive bleeding, hematoma, or infection. Because the information obtained from SMAD4 screening may have significant psychological effects, patients must be offered genetic counseling.
Results: Sequence analysis allows clinicians to identify the specific DNA mutation(s) present in a JPS patient. Once this mutation has been identified, close relatives can be screened to determine if they share the mutation that causes JPS. Routine colonoscopy and polypectomy, beginning at age fifteen, is recommended for those bearing mutations in SMAD4.
Bibliography
Calva, Daniel. “Juvenile Polyposis - Cancer Syndromes.” NCBI, 2009, www.ncbi.nlm.nih.gov/books/NBK51310. Accessed 30 June 2024.
Campbell, Harry, et al. "Colorectal Cancer." Human Genome Epidemiology: Building the Evidence for Using Genetic Information to Improve Health and Prevent Disease. Edited by Muin J. Khoury, et al. 2d ed., Oxford; New York: Oxford UP, 2010.
“Genetics of Colorectal Cancer (PDQ®) - PDQ Cancer Information Summaries - NCBI Bookshelf.” NCBI, 28 May 2024, www.ncbi.nlm.nih.gov/books/NBK126744. Accessed 30 June 2024.
“Juvenile Polyposis Syndrome.” MedlinePlus, 1 Oct. 2013, medlineplus.gov/genetics/condition/juvenile-polyposis-syndrome. Accessed 30 June 2024.
Sarshekeh, Amir M., et al. "Association of SMAD4 Mutation with Patient Demographics, Tumor Characteristics, and Clinical Outcomes in Colorectal Cancer." PLoS ONE, vol. 12, no. 3, 2017, doi.org/10.1371/journal.pone.0173345. Accessed 30 June 2024.
“SMAD4 Gene.” MedlinePlus, 1 Feb. 2020, medlineplus.gov/genetics/gene/smad4. Accessed 30 June 2024.
Xiong, Wenjing, et al. "Smad4 Deficiency Promotes Pancreatic Cancer Immunogenicity by Activating the Cancer-Autonomous DNA-Sensing Signaling Axis." Advanced Science, vol. 9, no. 7, 2022, p. 2103029, doi.org/10.1002/advs.202103029. Accessed 30 June 2024.
Xourafas, et al., Dimitrios. “The Impact of Somatic SMAD4 Mutations in Colorectal Liver Metastases.” Chinese Clinical Oncology, vol. 8, no. 5, 2019, cco.amegroups.org/article/view/28853/html. Accessed 30 June 2024.