Bidirectional Association Between Atrial Fibrillation and Ovarian Cancer: Evidence From the UK Biobank and Mendelian Randomization
Menée à l'aide d'une méthode de randomisation mendélienne et notamment de données de la "UK Biobank" portant sur 265 248 femmes (durée médiane de suivi : 17,8 ans), cette étude analyse l'association entre une fibrillation auriculaire et le risque de cancer de l'ovaire
Background: Atrial fibrillation (AF) and ovarian cancer (OCA) are leading causes of morbidity, with emerging evidence suggesting potential interplay. However, their temporal and genetic relationships remain unclear.
Methods: We analyzed 265,248 women from the UK Biobank using bidirectional Cox models to examine associations between AF and OCA. Two-sample Mendelian randomization (MR) assessed genetically proxied AF liability on OCA risk, complemented by summary-data–based MR (SMR) and functional genomic analyses to identify shared genes. Loss-of-function assays in SKOV3 OCA cells evaluated biological plausibility.
Results: During a median 17.8-year follow-up, both directions showed significant associations: AF increased OCA risk (HR 1.30, 95% CI 1.05–1.61), and OCA 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 OCA (OR 1.05, 95% CI 1.00–1.11), with directionality confirmed by MR-Steiger tests. SMR and integrative analyses identified NUP50 and SYTL2 as shared susceptibility genes, whose knockdown inhibited proliferation of OCA cells.
Conclusions: This study provides complementary observational and genetic evidence linking AF and OCA. While bidirectional associations were observed in the UK Biobank cohort, Mendelian randomization analyses supported a genetic contribution of AF liability to OCA risk but not the reverse. Integrative genomic analyses further nominated NUP50 and SYTL2 as potential mediators of the AF–OCA connection.
Impact: Women with AF may represent a high-risk group for OCA, highlighting the need for cardio-oncology surveillance and biomarker-guided screening strategies.
Cancer Epidemiology, Biomarkers & Prevention , article en libre accès, 2025