The GI genetics clinic and population-based screening for Lynch syndrome


This article was co-written with Dr. Caitlin Murphy. 

Once a mutation is confirmed, a personalized management program is developed for the patient based on national guidelines.

The UT Southwestern Cancer Genetics Program, in partnership with the Division of Digestive and Liver Diseases, provides specialized care for patients with high-risk gastrointestinal malignancies. Patients are evaluated by board-certified genetic counselors at UTSW Simmons Comprehensive Cancer Center or Parkland Hosital, then referred to the UTSW Digestive Diseases Clinic or the Gastrointestinal Cancer Genetics Clinic (respectively), both led by Dr. Ezra Burstein, to coordinate all aspects of their follow-up care.

Patients seen in this program include those with Lynch syndrome, one of the most common hereditary cancer syndromes, affecting 1 in 300 individuals. The syndrome is due to mutations affecting the function of proteins required to correct errors in our DNA. Defects in these genes can give rise to cancer in the colon, rectum, endometrium (the internal lining of the uterus), ovaries, stomach, and other locations.

In most individuals with Lynch syndrome, the condition is undiagnosed, leaving them unaware of their increased cancer risk. As a result, the Centers for Disease Control and Prevention (CDC) has determined that Lynch syndrome screening has significant potential to positively impact public health. The agency strongly encourages greater awareness and testing for this condition. 

Among the strategies to identify patients with Lynch syndrome, colorectal and endometrial tumors in patients under certain ages are now tested for molecular features of Lynch syndrome. This is important because:

  • Patients with those tumors who have Lynch syndrome face an increased risk of developing a second primary tumor in the same organ if left unmanaged
  • Since Lynch syndrome increases the risk of cancer in many organs in the body, these patients also are at risk of developing subsequent tumors in other organs 
  • Knowing that a tumor is due to underlying Lynch syndrome could affect treatment approaches such as immunotherapy
  • A Lynch syndrome diagnosis creates an opportunity for patients’ relatives to learn about the hereditary condition and consider undergoing screening themselves, with the hope of preventing cancer altogether

UT Southwestern Medical Center and Parkland Hospital were among the first medical centers in the country to institute a tumor-based Lynch syndrome immunohistochemical (IHC) screening test. 

Identifying patients with tumors that are characteristic of Lynch syndrome is just the first step. Once a mutation is identified and confirmed, a personalized management program is developed for the patient based on national guidelines.

IHC testing is performed on colorectal tumors and endometrial tumors to look for the loss of mismatch repair (MMR) proteins, which may indicate the hereditary defect causing Lynch syndrome. Through this screening protocol at UT Southwestern, Parkland, and other locations in North Texas, including John Peter Smith Hospital in Fort Worth, we have identified a large number of patients who need risk assessment and additional screening for cancer prevention.

Furthermore, through support from the Cancer Prevention and Research Institute of Texas, we have implemented outreach programs at UT Southwestern and Parkland to identify and contact patients cancer that may warrant genetic testing due to a strong family history of colorectal cancer (the DUAL prevention program). In our Cancer Genetics clinics, we are able to provide continuity of care for patients through every step of the process– from initial genetic risk assessment, to genetic testing, to diagnosis of an underlying hereditary cancer predisposition syndrome, to all aspects of follow-up surveillance and management indicated for that syndrome.

In providing care for cancer patients in a comprehensive clinic, we have observed 90 percent compliance with follow-up recommendations. Our high compliance is due in part to the use of medical information and tools readily available through electronic medical records. These tools allow for efficient and standardized communication and coordination of the patient’s care across the entire health care team.

Coupled with these clinical programs, UT Southwestern is also leading the way in research to understand the rising incidence of colorectal cancer in young people.  Among those under age 50 who are diagnosed with colorectal cancer, about 20% have a hereditary cancer syndrome, and most of these patients have Lynch syndrome. However, the remaining 80% of young patients with colorectal cancer have no known genetic cause or family history of the disease, as found by Dr. Caitlin Murphy.