One in 10 patients with a cancer of the appendix carries a germline genetic variant associated with a predisposition to cancer, according to a study published in JAMA Oncology who is the first to show hereditary risk factors for this rare cancer.
Appendix cancer affects about one or two people per million each year. Historically, appendix cancer was thought not to be hereditary, but its rarity has posed challenges to understanding the characteristics of the disease and developing therapies. A research team led by Andreana Holowatyj, PhD, MSCI, assistant professor of medicine and cancer biology at Vanderbilt University Medical Center, analyzed multigene panel test data from a clinical testing laboratory at the Vanderbilt University. ;national scale to United States for a total of 131 appendix cancer patients. They found that 11.5% of patients had at least one germline genetic variant in a embarrassed of susceptibility to cancer. Furthermore, among the subset of patients whose appendix cancer was the first and only primary tumour, they observed a similar prevalence (10.8%), which reinforces the link between the familial component and this sickness.
The results suggest that all patients with appendix cancer should consider genetic evaluation as well as cascade testing and genetic counseling to at-risk family members for cancer prevention and monitoring. However, further studies are needed to identify new genetic factors and use this evidence to fit selected genes in genetic testing for appendix cancer, Holowatyj said.
Based on these data, we are able to recommend genetic counseling and multi-gene panel testing of cancer susceptibility genes for all patients with appendix cancer, regardless of age or family history of cancer. cancer. Although there is still much to learn from our discovery, we have found the tip of an iceberg – potentially a very large iceberg.”
Andreana Holowatyj, PhD, MSCI, Assistant Professor of Medicine and Cancer Biology, Vanderbilt University Medical Center.
The study was published concurrently with Holowatyj’s presentation of his findings at the Collaborative Group of the Americas on Hereditary Gastrointestinal Cancer (CGA-IGC) annual meeting held in Nashville in 2022.
Although appendix cancer is rare, it is becoming more common for reasons that are not known. Last year, Holowatyj and his colleagues conducted the first study of appendix cancer characteristics and survival in patients under age 50 (early-onset disease) in the United States. They found that disease outcomes were worse in non-Hispanic blacks than in non-Hispanic whites, and in men than in women.
This study, which was published in Gastroenterologywas followed by another study led by Holowatyj, which compared the molecular landscapes of early-onset and late-onset appendix cancer. The second study, published in JAMA Network Openrevealed distinct non-silent mutations in tumors from younger patients, paving the way for potential therapeutic advances.
A third study, published in Cancer Epidemiology, Biomarkers & Prevention by Holowatyj’s groupfound that one in three cases of appendix cancer occurs in people under the age of 50, and that these early cases have distinct clinical features from those in people aged 50 and over.
Holowatyj and the research team received support from the Dalton Family Foundation and the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health.
The other Vanderbilt researchers who co-authored the study are Mary K. Washington, MD, PhD, and Cathy Eng, MD.
People who have been diagnosed with appendix cancer and wish to participate in a clinical research study – the GAP (Genetics of Appendix Cancer) study – are invited to visit the following site www.gapcancerstudy.org.