Appraisal of the causal effect ofChlamydia trachomatisinfection on epithelial ovarian cancer risk: a two-sample Mendelian randomisation study

Background History of Chlamydia trachomatis infection has previously been associated with epithelial ovarian cancer (EOC) in observational studies. We conducted a two-sample univariable Mendelian randomisation (MR) study to examine whether genetically predicted seropositivity to the C. trachomatis major outer membrane protein (momp) D is causally associated with EOC. Methods MR analyses employed genetic associations derived from UK Biobank as proxies for momp D seropositivity in 25 509 EOC cases and 40 941 controls that participated in the Ovarian Cancer Association Consortium. Findings were replicated using a GWAS meta-analyses of global biobanks including the UK Biobank, FinnGen and BioBank Japan. Results Genetically predicted momp D seropositivity was associated with overall and high-grade serous EOC risk in inverse-variance weighted (IVW) and MR-Egger univariable MR analysis (odds ratio (OR) 1.06; 95% confidence interval (CI) 1.02—1.10, and OR 1.08; 95%CI 1.01—1.16, respectively). Replication yielded similar results for overall EOC (OR 1.11; 95%CI 1.01—1.22). Conclusion This MR study supports a causative link between C. trachomatis infection and overall and high-grade serous EOC.