Abstract 77P
Background
History of Chlamydia trachomatis infection has previously been associated with epithelial ovarian cancer (EOC) in observational studies. The existing evidence base is deficient due to challenges in study design, influenced by residual confounding factors and small study populations, and it has not been possible to determine whether observed associations are causal. Mendelian randomisation (MR) is an epidemiological strategy aimed at removing potential biases which exist within conventional observational studies. This method uses single nucleotide polymorphisms (SNPs) as instrumental variables, enabling potential causal relationships between an exposure and outcome to be determined. To our knowledge, MR has never been used to explore this association.
Methods
We used a two-sample univariable MR approach to investigate the causal relationship between seropositivity to the C. trachomatis major outer membrane protein (momp) D antibody and EOC. MR analyses employed genetic associations derived from the 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 (OCAC). Findings were replicated using a GWAS meta-analyses of global biobanks including the UK Biobank and FinnGen.
Results
Ten SNPs were identified to be associated with momp D seropositivity using the UK Biobank as the reference panel. Genetically-predicted momp D risk was associated with overall and high-grade serous EOC in inverse-variance weighted MR analysis using OCAC data (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 using UK Biobank and FinnGen yielded similar results for overall EOC (OR 1.11; 95%CI 1.01—1.22).
Conclusions
This MR study confirms the causative link between C. trachomatis infection and overall and high-grade serous EOC. As a key modifiable risk factor for future serous EOC, primary prevention of C. trachomatis infection is a crucial public health target and may help reduce burden of EOC.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.