Research Snapshot: UF study finds younger patients with colorectal cancer less likely to have targetable genetic mutations

A new study led by University of Florida researchers found that while younger patients with colorectal cancer were significantly more likely to be diagnosed with advanced stage colorectal malignancies, these patients had significantly lower rates of genetic mutations, decreasing the number of effective, approved drugs that are available for treatment. Universal genetic testing at UF Health identified a relatively large population of older patients with sporadic colorectal cancer who were eligible for immunotherapy, emphasizing the importance of testing all patients.

colorectal researchers
Top row left to right: Ellery Altshuler, M.D., Aaron Franke, M.D., and Thomas George, M.D., FACP. Bottom row left to right: Ji-Hyun Lee, DrPH, XiangYang Lou, Ph.D., and Krista Terracina, M.D.

The findings, published recently in the journal Clinical Colorectal Cancer, highlight that much remains unknown about the genetic risk factors for colorectal cancer as more young people are diagnosed with advanced disease, the researchers reported.

The study, conducted by a transdisciplinary team from several departments and research units across the UF Health Cancer Center, analyzed the samples of 375 patients over an eight-year period after universal genetic testing for colorectal cancer was implemented at UF Health in 2009. Younger patients were defined as those younger than 50 years old. Testing was conducted by immunohistochemistry, polymerase chain reaction and next-generation sequencing.

The team found colorectal cancers were mismatch repair deficient (dMMR)/microsatellite instability high (MSI-H) in 12% of younger patients compared to 21% of older patients. The researchers also found a markedly higher rate of tumors harboring pathogenic BRAF v600E mutations in the older than the younger patient populations (16% vs. 1.5%). The findings of higher rates of targetable and clinically relevant genetic abnormalities in older patients were in keeping with other studies on the topic, but the gap was larger than other reports, the team reported.

The authors concluded that implementing reflex MMR/MSI testing in colorectal cancer is feasible at an institutional level. In the authors’ dataset, younger patients with colorectal cancer were diagnosed with more advanced disease and had stage IV dMMR/MSI-H cancers at the rate expected. However, universal/reflex testing identified dMMR/MSI-H cancers at a higher than expected rate in patients older than 50. Ongoing analyses of this approach to testing and further studies to identify risk factors for colorectal cancer development in younger patients are needed, the team said. Additionally, it will be important to determine the clinical impact of universal reflex testing on patient outcomes to ensure optimal immune checkpoint inhibitor therapy consideration, use of genetic counseling and tailored treatments, the researchers wrote.

Authors from the UF Health Cancer Center were Aaron J. Franke, M.D., assistant professor in the division of hematology and oncology in the College of Medicine; Ji-Hyun Lee, DrPH, professor in the department of biostatistics in the College of Public Health & Health Professions and director of the division of quantitative sciences at the Cancer Center; XiangYang Lou, Ph.D., professor in the department of biostatistics; Krista Terracina, M.D., assistant professor in the department of surgery in the College of Medicine; and Thomas George, M.D., FACP, professor in the division of hematology and oncology and the study’s senior author. Ellery Altshuler, M.D., an internal medicine resident, was the primary author.


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