Proteogenomic and observational evidence implicate ANGPTL4 as a potential therapeutic target for colorectal cancer prevention.

ABSTRACT:

Background

The role of lipid-perturbing medications in cancer risk is unclear.

Methods

We employed cis-Mendelian randomization and colocalization to evaluate the role of 5 lipid-perturbing drug targets (ANGPTL3, ANGPTL4, APOC3, CETP, and PCSK9) in risk of 5 cancers (breast, colorectal, head and neck, ovarian, and prostate). We triangulated findings using pre-diagnostic protein measures in prospective analyses in EPIC (977 colorectal cancer cases, 4080 sub-cohort members) and the UK Biobank (860 colorectal cancer cases, 50 177 controls). To gain mechanistic insight into the role of ANGPTL4 in carcinogenesis, we examined the impact of the ANGPTL4 p. E40K loss-of-function variant on differential gene expression in normal colon tissue in BarcUVa-Seq. Finally, we evaluated the as

SUBMITTER: Yarmolinsky J 

PROVIDER: S-EPMC12415964 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature