Andreana N. Holowatyj, PhD, MSCI, an assistant professor of medicine and cancer biology at Vanderbilt University Medical Center and Vanderbilt-Ingram Cancer Center (VICC) discusses results from an investigation of germline genetic features that may confer cancer susceptibility in patients with appendiceal cancer.

Although there is still uncertainty regarding the clinicopathologic risk factors for the development of early-onset appendiceal cancer, most experts have historically believed that this tumor type is not hereditary, according to Holowatji. However, recent data demonstrating a disproportionate degree of early-onset disease burden indicates that hereditary factors may play a role in this tumor type.

To evaluate potential genetic predisposition for appendiceal cancer, Holowatyj and her colleagues at VICC assessed the prevalence and spectrum of inherited cancer susceptibility gene variants in patients with appendiceal cancer through germline genetic testing. A total of 14 genes associated with gastrointestinal (GI) cancer susceptibility were identified. The study enrolled 131 patients regardless of age or family history of cancer. Of these patients, 75% had a first primary appendix tumor, and 7 out of every 8 patients reported a family history of cancer.

Germline testing of these patients revealed that approximately 1 in 10 patients (11.5%) carried 1 of 16 deleterious GI cancer susceptibility variants, Holowatyj says. After limiting testing to 74 patients with appendiceal cancer as the first and only primary tumor, 10.8% of these patients were found to have at least 1 deleterious mutation in a cancer susceptibility gene, she emphasizes.

It is important to note the limitations of this study, Holowatji adds. No methods were utilized to detect mutations that are 100% sensitive, and the discovery of some deleterious variants in non–Lynch syndrome genes may be incidental, Holowatji says. Additionally, patients with a family cancer history may have been overrepresented in this cohort, she explains.

Still, these results open up future avenues for novel gene discovery related to appendiceal cancer predisposition, and support continued attempts to investigate the role of hereditary features in this tumor type, Holowatji states. Findings also show the utility of germline testing for all patients diagnosed with this malignancy irrespective of age or family cancer history, which could influence the use of this tool in clinical practice, she concludes.

Dr Holowatyj reports receiving grants from The Dalton Family Foundation, the National Institutes of Health (NIH), Pfizer, the American Cancer Society and the Appendix Cancer Pseudomyxoma Peritonei (ACPMP) Research Foundation. She also chairs the Scientific Advisory Board for the ACPMP Research Foundation.

Videos

Andreana N. Holowatyj, PhD, MSCI, discusses results from an investigation of germline genetic features that may confer cancer susceptibility in patients with appendiceal cancer.

Andreana N. Holowatyj, PhD, MSCI

Articles

Dr Holowatyj on the Potential Role of Germline Genetic Features in Appendiceal Cancer Susceptibility