Clinical syndromes linked to biallelic germline variants in MCM8 and MCM9.

ABSTRACT: MCM8 and MCM9 are newly proposed cancer predisposition genes, linked to polyposis and early-onset cancer, in addition to their previously established association with hypogonadism. Given the uncertain range of phenotypic manifestations and unclear cancer risk estimates, this study aimed to delineate the molecular and clinical characteristics of biallelic germline MCM8/MCM9 variant carriers. We found significant enrichment of biallelic MCM9 variants in individuals with colonic polyps (odds ratio [OR] 6.51, 95% confidence interval [CI] 1.24-34.11, p = 0.03), rectal polyps (OR 8.40, 95% CI 1.28-55.35, p = 0.03), and gastric cancer (OR 27.03, 95% CI 2.93-248.5; p = 0.004) in data from the 100000 Genomes Project, compared to controls. No similar enrichment was found for biallelic MCM8 variants

SUBMITTER: Helderman NC 

PROVIDER: S-EPMC12361757 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature