The following is a summary of “Genetic Risk Factors for Early-Onset Merkel Cell Carcinoma,” published in the January 2024 issue of Dermatology by Mohsin, et al.
Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine skin cancer, with only 4% of annual cases occurring in individuals younger than 50 years. For a study, researchers sought to identify genetic risk factors associated with early-onset MCC through genomic sequencing.
The study was collaborative between the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National Institute of Allergy and Infectious Diseases (NIAID), and the University of Washington. Participants with early-onset and later-onset MCC were prospectively enrolled at the University of Washington between January 2003 and May 2019. Unrelated controls were enrolled in the NIAID Centralized Sequencing Program (CSP) between September 2017 and September 2021. Analysis of the data was conducted between September 2021 and March 2023. Early-onset MCC was defined as disease occurrence in individuals younger than 50 years, while later-onset MCC was defined as occurring at age 50 years or older. Unrelated controls were individuals evaluated by the NIAID CSP for disorders unrelated to familial cancer syndromes.
The analysis included 1,012 participants, comprising 37 with early-onset MCC, 45 with later-onset MCC, and 930 unrelated controls. Among the 37 patients with early-onset MCC, 7 (19%) had well-described variants in genes associated with cancer predisposition. Specifically, six patients had variants linked to hereditary cancer syndromes (ATM = 2, BRCA1 = 2, BRCA2 = 1, TP53 = 1), and one patient had a variant associated with immunodeficiency and lymphoma (MAGT1). Compared to the 930 unrelated controls, the early-onset MCC group showed significant enrichment for cancer-predisposing pathogenic or likely pathogenic variants in these five genes (odds ratio, 30.35; 95% CI, 8.89-106.30; P < .001). No germline disease variants in these genes were found in the 45 patients with later-onset MCC. Additionally, other variants in DNA repair genes were identified among MCC patients.
Given the association between certain DNA repair and cancer predisposition genes with early-onset MCC, genetic counseling and testing should be considered for patients presenting younger than 50 years.
Reference: jamanetwork.com/journals/jamadermatology/article-abstract/2813276