Should we Perform Germline Genetic Testing in Patients with Appendiceal Cancer?

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Based on the known yield of germline genetic testing in patients with colorectal cancer, professional societies currently recommend genetic testing in all patients diagnosed with colorectal under age 50, and are now expanding germline genetic testing in colorectal cancer patients of all ages. A clinical question that commonly arises is whether patients with appendiceal cancer have a similar germline spectrum as patients with colon cancer.

Although the appendix is a protrusion from the colon, appendiceal cancers appear to have a different biology and risk factors than colon cancers, thus it is unknown if appendix cancers have the same genetic spectrum.

Dr. Andreana N. Holowatyj and colleagues sought to describe the germline genetic spectrum of appendiceal cancers, in their research study entitled “Inherited Cancer Susceptibility Gene Sequence Variations Among Patients With Appendix Cancer.” Their findings were presented at the Collaborative Group of the Americas on Inherited Gastrointestinal Cancers (CGA-IGC) Annual Meeting in Nashville, TN, on November 11th 2022, and also published in the Journal of the American Medical Association (JAMA) Oncology[PS1] .

Their study included 131 patients with appendix cancer who underwent 14-gene panel testing. They found that 11.5% carried a pathogenic variant in a gene associated with cancer risk; 6.1% had a high-risk variant (4 with MLH1 Lynch Syndrome, 1 with biallelic MUTYH, 1 APC, 1 SMAD4, 1 TP53) and 5.3% had a moderate penetrance variant (5 monoallelic MUTYH, 2 CHEK2). The authors concluded that patients with appendiceal cancer may benefit from germline genetic testing.

Dr. Swati G Patel from the University of Colorado states “This study answers the important and common clinical question of what we would find if we performed germline genetic testing in appendiceal cancer patients. The trickier question is whether this data supports genetic testing in all appendiceal cancer patients. The answer likely depends on the health setting, which would balance the likelihood of finding a result that would actually change management for patients and their families, with the cost and availability of testing. This is a decision that will be setting and system-specific. Nonetheless, this study answers a question we discuss all the time, thus is a very important contribution to the literature.”

The full article can be accessed at JAMA Oncology.

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