Abstract 362P
Background
The gut microbiota has been recognized as tumor biomarkers for various cancers, and specific tumor markers can be discovered through causal relationships. The causal relationships between gut microbiota and prostate cancer remained uncertain. We intend to identify the causal connections between gut microbiota and prostate cancer and investigate the potential underlying mechanisms.
Methods
A two-sample Mendelian randomization (MR) analysis was conducted to elucidate the impact of 196 gut microbiota on prostate cancer. The reverse MR, linkage disequilibrium regression score (LDSC), and colocalization analyses were performed to strength causal evidence. A phenome-wide MR (Phe-MR) analysis evaluated potential side effects targeting the detected gut microbiota. We designed a two-step MR study to assess the mediation effects of circulating cytokines, sex hormones, and blood metabolites.
Results
In the MR analyses, 11 bacterial taxa were causally associated with prostate cancer. In these bacterial taxa, Alphaproteobacteria (OR = 0.87 95% CI, 0.76-0.96, P = 0.004) restrained prostate cancer and Paraprevotella (OR = 1.08 95% CI, 1.00-1.17, P = 0.044) had a risk effect on prostate cancer. In reverse MR analysis, gut microbiota abundance was unaffected by prostate cancer. LDSC and colocalization analyses indicated that the detected associations would not be confounded by genetic correlation or LD from common causal loci. The Phe-MR analysis showed no apparent tox or side effects on the identified gut microbiota. In the mediation analysis, we found 7 mediators linking gut microbiota to prostate cancer, with a specific emphasis on the critical roles played by sex hormones and blood metabolites.
Conclusions
Our study represented the first comprehensive exploration of the gut microbiota's causal effects on prostate cancer and revealed the mediating effects of sex hormones and blood metabolites in the “gut-prostate axis.” Our study has contributed to the discovery of tumor biomarkers in the gut microbiota for prostate cancer, providing a basis for early screening and treatment of the disease.
Clinical trial identification
Editorial acknowledgement
We acknowledge the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome consortium (PRACTICAL) for providing GWAS data of prostate cancer. We want to acknowledge the participants and investigators of the FinnGen study. We thank the Mathematical Medicine Integration Innovation Training Program for Undergraduate Students (MITUS) for providing valuable guidance, support, research opportunities, and resources. Thanks to Yunyun Mei for his work in the Mendelian Randomization analysis, we made use of the R package of his developed easyMR. His excellent sharing of Mendelian Randomization analysis procedure makes it easier for us to explore the post-GWAS database.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.