Identifying risk factors of biliary tract cancers using a large Japanese regional insurance claims database

Biliary tract cancers (BTCs), including bile duct cancer (BDC), gallbladder cancer (GC), and ampullary cancer (AC), are characterized by poor prognosis and increasing incidence. Identifying risk factors is essential for early detection, yet few studies have evaluated multiple risk factors for BTCs comprehensively within a large cohort. This study investigated risk factors for BTC subtypes using a large regional database from Shizuoka Prefecture, Japan. A cohort of 2,571,418 individuals was analyzed based on insurance claims from April 2012 to September 2021. Participants without medical checkups or with an observation period of less than one year were excluded, leaving 625,513 eligible participants. BTC incidence was assessed using multivariate Cox proportional hazards regression, incorporating health checkup data and comorbidities. Over a median follow-up of 6.2 years, 1433 cases of BDC, 838 cases of GC, and 205 cases of AC were identified. Shared risk factors across BTC subtypes included older age, male sex, elevated liver function, and cardiometabolic conditions such as hypertension and diabetes. Subtype-specific risk factors were also observed: hepatitis virus infection for BDC, bile duct stones for BDC and GC, gallbladder stones for GC, and rheumatic disease for AC. These findings emphasize both common and unique risk factors for BTC subtypes.