Carcinogenic risk in the biliary epithelium of children with congenital biliary dilatation via the DNA damage repair pathway

Abstract Background: Congenital biliary dilatation (CBD) is a high-risk factor for biliary tract cancer (BTC). We have previously reported the potential for carcinogenesis in the biliary epithelium of patients with CBD. In this study, we investigated potential carcinogenetic pathways, focusing on the DNA damage repair response, in children with CBD and compared the findings with adults.Methods: We enrolled six children with CBD and 10 adults with CBD without BTC who underwent extrahepatic bile duct resections, plus four control patients who underwent pancreaticoduodenectomy for non-biliary cancer. Levels of phosphorylated histone H2AX (γH2AX), MRE11, and Ku-70 in the biliary tract epithelium were evaluated by immunohistochemistry.Results: Levels of γH2AX, MRE11, and Ku-70 were significantly higher in the gallbladder epithelium and bile duct epithelium of both children and adults compared with in controls. Conclusions: Children and adults with CBD might develop BTC via the DNA damage repair pathway, as evidenced by increased γH2AX, MRE11, and Ku-70 expression.