Epidemiological Trends and Germline Variant Analysis of Young-Onset Bladder Cancer

BACKGROUND: The incidence of bladder cancer (BCa) is rising worldwide. Recent reports suggest a disproportionate increase among younger individuals, raising questions about epidemiologic and genetic contributors to early-onset disease. We aimed to characterize incidence and prevalence trends across younger and older populations and to evaluate germline genetic factors associated with young-onset bladder cancer (YOBC). PATIENTS AND METHODS: Using the TriNetX research network, we analyzed BCa incidence and prevalence trends from 2011 to 2023, stratified by age and sex. Germline variant data from the UK Biobank (UKBB) were analyzed to identify genetic associations in YOBC using a genome-wide regression approach. RESULTS: TriNetX identified 299,272 patients with BCa. Among individuals aged ≥50 years, incidence increased steadily, with male predominance. In contrast, the