摘要:
Background Dysbiosis of gut microbiota has been linked to numerous diseases, including cancer. The unique role
of gut microbiota in urological tumors is gaining prominence. However, it is still controversial whether the dysbiosis
of gut microbiota should be one of the etiological factors of bladder cancer (BCa), prostate cancer (PCa) or kidney
cancer (KCa).
Materials and methods The microbiome genome-wide association study (GWAS) from the MiBioGen consortium
(18,340 samples of 24 population-based cohorts) was utilized as the exposure data. Additionally, outcomes data (951
BCa cases and 307,092 controls; 1,631 KCa cases and 238,678 controls; 79,148 PCa cases and 61,106 controls) were
extracted from the GWAS of the FinnGen and PRACTICAL consortia. To detect the potential causative bacterial traits
for BCa, PCa, and KCa, a two-sample Mendelian randomization (MR) analysis was performed, employing the inversevariance weighted or Wald ratio method. Sensitivity analyses were subsequently conducted to explore the robustness
of the primary results. Finally, the reverse MR analysis was undertaken to mitigate the reverse causation.
Results This study suggested that Bifdobacterium (p=0.030), Actinobacteria (p=0.037 for phylum, 0.041
for class), and Ruminococcustorques group (p=0.018), exhibited an association with an increased risk of BCa using
either the inverse-variance weighted or Wald ratio method. By utilizing the Wald ratio method, Allisonella (p=0.004,
p=0.038) was associated with a decreased risk of BCa and PCa, respectively. Furthermore, Ruminococcustorques group
(p=0.028) and Erysipelatoclostridium (p=0.048) were causally linked to an elevated risk of KCa.
Conclusions This MR study supports that genetically predicted gut microbiota is causally related to BCa, PCa
and KCa. Additionally, distinct bacterial traits are identifed in relation to each tumor type