Patients with periodontitis might increase the risk of urologic cancers: a bidirectional two-sample Mendelian randomization study

Int Urol Nephrol. 2024 Apr;56(4):1243-1251. doi: 10.1007/s11255-023-03858-w. Epub 2023 Nov 28.

Abstract

Background: Numerous observational epidemiological studies have reported a bidirectional relationship between periodontitis and urological cancers. However, the causal link between these two phenotypes remains uncertain. This study aimed to examine the bidirectional causal association between periodontitis and four types of urological tumors, specifically kidney cancer (KC), prostate cancer (PC), bladder cancer (BC), and testis cancer (TC).

Methods: Based on large-scale genome-wide association study (GWAS) data, we utilized the two-sample Mendelian randomization (MR) approach to evaluate causal relationships between periodontitis and urological cancers. Several MR methods covering various consistency assumptions were applied in this study, including contamination mixture and Robust Adjusted Profile Score to obtain robust results. Summary-level data of individuals with European ancestry were extracted from the UK Biobank, the Kaiser GERA cohorts, and the FinnGen consortium.

Results: Our findings revealed significant positive genetic correlations between periodontitis and kidney cancer (OR 1.287; 95% CI 1.04, 1.594; P = 0.020). We did not find a significant association of periodontitis on prostate cancer, bladder cancer, and testis cancer. In reverse MR, no significant results were observed supporting the effect of urologic cancers on periodontitis (all P > 0.05).

Conclusion: Our study provides the evidence of a potential causal relationship between periodontitis and kidney cancer. However, large-scale studies are warranted to confirm and elucidate the underlying mechanisms of this association.

Keywords: Causal relationship; Genetic epidemiology; Immunity; Mendelian randomization; Periodontitis; Urologic neoplasms.

MeSH terms

  • Carcinoma, Renal Cell*
  • Genome-Wide Association Study
  • Humans
  • Kidney Neoplasms* / epidemiology
  • Kidney Neoplasms* / genetics
  • Male
  • Mendelian Randomization Analysis
  • Periodontitis* / epidemiology
  • Periodontitis* / genetics
  • Prostatic Neoplasms* / epidemiology
  • Prostatic Neoplasms* / genetics
  • Testicular Neoplasms*
  • Urinary Bladder Neoplasms* / epidemiology
  • Urinary Bladder Neoplasms* / genetics
  • Urologic Neoplasms* / epidemiology
  • Urologic Neoplasms* / genetics