New-Onset Atrial Fibrillation as a Predictor of Cancer: Insights from a Real-World Dataset.

Background: A bidirectional relationship between atrial fibrillation (AF) and cancer has been suggested, but the mechanisms and directionality remain poorly understood.

Objectives: To examine the relationship between new-onset AF and incident cancer across different age groups.

Methods: This retrospective study utilized the TriNetX research network. Patients with hypertension, type II diabetes, or coronary artery disease were included and stratified by the presence of AF. Individuals with prior malignancy were excluded. Patients were categorized into three age groups: 30-50, 50-70, and 70-85 years and matched 1:1 using propensity scores. The primary outcome was all-cause cancer incidence, with secondary analyses of site-specific malignancies. Risk ratios, Kaplan-Meier survival analysis, and multivariable Cox regression models were used. Follow-up was up to 15 years after AF diagnosis.

Results: Matched cohort sizes were: 30-50 (n=67,156 per group), 50-70 (n=510,308), and 70-85 (n=882,729). AF was associated with increased cancer risk: RR 2.99, 1.79, and 1.49 across increasing age groups (all p<0.001). Kaplan-Meier analyses showed decreased cancer-free survival: HR 2.96, 1.84, and 1.53 across increasing age groups (all p<0.001). Sensitivity analyses excluding cancers diagnosed within the first 3 months and after the first year of AF onset, comparing AF subtypes, and using multivariable Cox models confirmed consistent associations.

Conclusion: AF is associated with an increased risk of incident cancer, particularly in younger individuals.