Early-onset MCC was 'significantly enriched' in cancer predisposing variants in 5 specific genes.

New research indicates that germline variants in genes are significantly associated with early-onset Merkel cell carcinoma (MCC). 

The case-control study included 1,012 individuals (37 of whom had early-onset MCC, 45 with later-onset MCC, and 930 controls) who were prospectively enrolled in the study at the University of Washington between 2003 and 2019. The researchers defined early-onset MCC as disease occurrence in individuals younger than 50 years, and later-onset MCC as that which develops at age 50 or older. 

Among the individuals with early-onset MCC, seven (19%) had variants in their genes that are linked with a predisposition for cancer. Six patients had variants linked with hereditary cancer syndromes (ATM, BRCA1, BRCA2 , and TP53 ), and one had a variant linked with immunodeficiency and lymphoma (MAGT1). Within these 5 genes, according to the researchers, early-onset MCC was 'significantly enriched' for cancer-predisposing or likely pathogenic variants (OR, 30.35; 95% CI, 8.89 to 106.30; P < 0.001). They also identified no germline disease variants in genes of the 45 patients who developed later-onset MCC, as well as additional variants in DNA repair genes among patients with MCC.

"Because variants in certain DNA repair and cancer predisposition genes are associated with early-onset MCC, genetic counseling and testing should be considered for patients presenting at younger than 50 years," the authors wrote. 

Source

Mohsin N, Hunt D, Yan J, MS, et al. JAMA Dermatol. Published online January 3, 2024. doi:10.1001/jamadermatol.2023.5362