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Appraisal of the causal effect of Chlamydia trachomatis infection on epithelial ovarian cancer risk: a two-sample Mendelian randomisation study

Perrott, S. L.; Kar, S. P.

2024-10-14 epidemiology
10.1101/2024.10.13.24315417 medRxiv
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BackgroundHistory 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. MethodsMR 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. ResultsGenetically 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). ConclusionThis MR study supports a causative link between C. trachomatis infection and overall and high-grade serous EOC.

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