Pharmacological targets of SGLT2 inhibition on prostate cancer mediated by circulating metabolites: a drug-target Mendelian randomization study.

ABSTRACT:

Background

The relationship between sodium-glucose cotransporter 2 (SGLT2) inhibitors and prostate cancer is still unknown. Although these inhibitors can influence tumor glycolysis, the underlying mechanism requires further exploration.

Methods

A two-sample two-step MR was used to determine 1) causal effects of SGLT2 inhibition on prostate cancer; 2) causal effects of 1,400 circulating metabolites or metabolite ratios on prostate cancer; and 3) mediation effects of these circulating metabolites. Genetic proxies for SGLT2 inhibition were identified as variants in the SLC5A2 gene and glycated hemoglobin level (HbA1c). Additionally, positive control analysis on type 2 diabetes mellitus (T2DM) was conducted to test the selection of genetic proxies. Phenome Wide Association Study

SUBMITTER: Lin Y 

PROVIDER: S-EPMC11333260 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature