Mapping Inherited Genetic Variation with Opposite Effects on Autoimmune Disease and Four Cancer Types Identifies Candidate Drug Targets Associated with the Anti-Tumor Immune Response.

ABSTRACT: Background: Germline alleles near genes encoding certain immune checkpoints (CTLA4, CD200) are associated with autoimmune/autoinflammatory disease and cancer, but in opposite ways. This motivates a systematic search for additional germline alleles with this pattern with the aim of identifying potential cancer immunotherapeutic targets using human genetics. Methods: Pairwise fixed effect cross-disorder meta-analyses combining genome-wide association studies (GWAS) for breast, prostate, ovarian and endometrial cancers (240,540 cases/317,000 controls) and seven autoimmune/autoinflammatory diseases (112,631 cases/895,386 controls) coupled with in silico follow-up. Results: Meta-analyses followed by linkage disequilibrium clumping identified 312 unique, indepe

SUBMITTER: Chen J 

PROVIDER: S-EPMC12111551 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature