Abstract 370P
Background
Glucagon-like peptide-1 receptor agonists (GLP-1RA) are extensively utilized in the management of diabetes and obesity, with emerging evidence supporting their role in attenuating inflammation. Nonetheless, the causal associations between GLP-1RA and common cancers remained uncertain.
Methods
The expression quantitative trait loci (eQTLs) for target genes GLP-1R were sourced from eQTLGen and used as proxies for GLP-1RA exposure. Summary-level statistics for 13 cancers were extracted from publicly available genome-wide association studies (GWAS) with sample sizes ranging from 18,313 to 462,933 individuals. We utilized a summary-data-based Mendelian randomization (SMR) to assess the association between GLP-1R and the risk of these cancers, followed by a two-sample Mendelian randomization (TSMR) analysis as validation analysis. Additionally, a proteome-wide MR analysis involving 4907 proteins was conducted to explore the relationships between GLP-1R and cancer-associated proteins. A two-step network MR analysis was also performed to investigate the mediating role of protein pathways in these associations.
Results
Genetically predicted GLP-1R expression was solely associated with a reduced risk of prostate cancer, as confirmed by both SMR (Odds Ratio [OR] = 0.995, P = 0.047) and TSMR (OR = 0.98, P = 0.02) analyses. No causal relationships were found between GLP-1R and other cancers. The proteome-wide MR analysis identified 60 protein profiles linked to prostate cancer. Among them, GLP-1R was associated with 9 cancer-associated proteins. Activating Transcription Factor 6 (ATF6), Nudix Hydrolase 12 (NUDT12), and Repulsive Guidance Molecule A (RGMA) stood out among the mediating networks between GLP-1R and prostate cancer.
Conclusions
This study demonstrated that GLP-1RA decrease the risk of prostate cancer. Furthermore, the association between GLP-1RA and prostate cancer had been clarified through alterations in blood protein levels, providing insights into strategies for prostate cancer prevention and treatment.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.