| Title: | Bidirectional Association between Atrial Fibrillation and Ovarian Cancer: Evidence from the UK Biobank and Mendelian Randomization |
| Journal: | Cancer Epidemiology Biomarkers & Prevention |
| Published: | 7 Nov 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/41201259/ |
| DOI: | https://doi.org/10.1158/1055-9965.epi-25-0949 |
| URL: | https://aacrjournals.org/cebp/article-pdf/doi/10.1158/1055-9965.EPI-25-0949/3669634/epi-25-0949.pdf |
Publication 18987
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Abstract
BACKGROUND: Atrial fibrillation (AF) and ovarian cancer are leading causes of morbidity, with emerging evidence suggesting potential interplay. However, their temporal and genetic relationships remain unclear.</p>
METHODS: We 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.</p>
RESULTS: During 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.</p>
CONCLUSIONS: This 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.</p>
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.</p>
12 Keywords
- Aged
- Atrial Fibrillation
- Biological Specimen Banks
- Female
- Genetic Predisposition to Disease
- Humans
- Mendelian Randomization Analysis
- Middle Aged
- Ovarian Neoplasms
- Risk Factors
- UK Biobank
- United Kingdom
11 Authors
- Zhixuan Zhang
- Na Zhang
- Xinning Guo
- Zhengyu Tao
- Chen Wu
- Qiming Liu
- Ling Ding
- Wutao Chen
- Yu Zhong
- Meng Jiang
- Jun Pu
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