Abstract
INTRODUCTION: Multiple studies suggest a link between ankylosing spondylitis (AS) and endometrial cancer (EC), but causality is uncertain. METHOD: We used genome-wide association studies (GWAS) data in a Mendelian randomization analysis, primarily inverse variance weighting, to investigate if genetically determined AS affects EC risk, with sensitivity analyses for heterogeneity and pleiotropy. RESULTS: The IVW results showed a possible causal association between AS and EC (non-endometrioid histology) (OR = 1.05, 95% CI 1.01-1.1, P = 0.02), while there was no significant association between AS and the risks of EC (endometrioid histology) (OR = 0.99, 95% CI 0.97-1.01, P = 0.35) with EC (OR = 0.99, 95% CI 0.98-1.01, P = 0.34). The analysis results of MR Egger, weighted median, simple mode and weighted mode for AS and EC (non-endometrioid histology) were insignificant. No statistically significant heterogeneity or horizontal pleiotropy was detected. CONCLUSIONS: This MR analysis did not reveal a substantial association between AS and overall EC or EC of endometrioid histology. Conversely, a significant causal connection between AS and non-endometrioid histology EC was identified. Additional research to are needed to explore the mechanisms of the relationship between AS and EC with the non-endometrioid subtype.