ArticleCancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology2026
Bidirectional Association between Atrial Fibrillation and Ovarian Cancer: Evidence from the UK Biobank and Mendelian Randomization.
Article in Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundAtrial fibrillation (AF) and ovarian cancer are leading causes of morbidity, with emerging evidence suggesting potential interplay. However, their temporal and genetic relationships remain unclear.
methodsWe analyzed 265,248 women from the UK Biobank using bidirectional Cox models to examine associations between AF and ovarian cancer. Two-sample Mendelian randomization (MR) assessed genetically proxied AF liability on ovarian cancer risk, complemented by summary data-based MR and functional genomic analyses to identify shared genes. Loss-of-function assays in SKOV3 ovarian cancer cells evaluated biological plausibility.
resultsDuring a median 17.8-year follow-up, both directions showed significant associations: AF increased ovarian cancer risk [HR, 1.30; 95% confidence interval (CI), 1.05-1.61], and ovarian cancer increased AF risk (HR, 1.75; 95% CI, 1.43-2.14), particularly for serous histotypes. MR analyses indicated a modest genetic association between AF liability and ovarian cancer (OR, 1.05; 95% CI, 1.00-1.11), with directionality confirmed by MR-Steiger tests. Summary data-based MR and integrative analyses identified nucleoporin 50 and synaptotagmin-like 2 as shared susceptibility genes, in which knockdown inhibited the proliferation of ovarian cancer cells.
conclusionsThis study provides complementary observational and genetic evidence linking AF and ovarian cancer. Although bidirectional associations were observed in the UK Biobank cohort, MR analyses supported a genetic contribution of AF liability to ovarian cancer risk but not the reverse. Integrative genomic analyses further nominated nucleoporin 50 and synaptotagmin-like 2 as potential mediators of the AF-ovarian cancer connection. IMPACT: Women with AF may represent a high-risk group for ovarian cancer, highlighting the need for cardio-oncology surveillance and biomarker-guided screening strategies.
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