Work

Immune gene diversity and STING1 variants in shaping cancer immunity across different genetic ancestry populations

Year: 2026

Type: article

Abstract: As human populations migrated to diverse geographical regions, they encountered varying pathogens, leading to pronounced natural selection pressures on the immune system. Analysis of non-synonymous single-nucleotide polymorphisms (nsSNPs) across major geographically structured populations showed greater variation in immune-related genes than in non-immune genes, consistent with pathogen-driven selection, whereas cancer-related genes exhibited lower variation, reflecting the evolutionary conservation of critical cellular functions. We prioritized nsSNPs in pattern recognition receptor genes based on population diversity and their association with type I interferon (IFN) activity. Among the top-ranked variants were rs11554776, rs78233829, and rs7380824 in STING1, which demonstrated functional impacts on intrinsic cGAS-STING1-IFN signaling in cancer cells and potential influences on tumor immunity. We further conducted a genome-wide characterization of nsSNPs in immune-related genes across genetic ancestry populations and established a publicly accessible database. Our study suggests that genetic ancestry-related germline variations may influence cancer immunity and treatment, supporting their consideration in personalized medicine.

Source: Cell Reports

DOI: 10.1016/j.celrep.2025.116882