1.Chronic inflammation and infection of bile duct Long-term chronic inflammatory stimulation is the basis for the occurrence of bile duct cancer, because clinically all diseases associated with bile duct cancer can lead to chronic inflammation of bile duct. Long-term stimulation of biliary tract mucosa by certain substances in bile (such as metabolites of bile acids) leads to epithelial atypical hyperplasia. 2.Stones in bile duct and gallbladder 20%-57% of bile duct cancer patients are accompanied by gallstones, thus it is believed that chronic stimulation of stones may be a carcinogenic factor. 3.Ulcerative colitis It has been reported that the incidence of bile duct cancer in patients with ulcerative colitis is 10 times higher than that of the general population. Patients with cholangiocarcinoma with ulcerative colitis have an earlier age of onset of 20-30 years than the general population, with an average age of 40-45 years, and often have a long-term history of colitis, and chronic bacteraemia in the portal system of patients may be the cause of cholangiocarcinoma and PSC, and the lesions mostly affect the whole colon. 4.Cystic malformation of bile ducts (congenital bile duct dilatation) It has become a consensus that congenital bile duct cysts are prone to cancer, and the incidence of bile duct cancer in patients with congenital bile duct cysts is as high as 2.5% to 28%. Although 75% of bile duct cystic malformations show symptoms in infancy and childhood, as far as bile duct cancer is concerned, 3/4 of the patients are those who develop symptoms of bile duct cystic malformations in adulthood. Regarding the mechanism by which cystic malformation of the bile duct leads to bile duct cancer, it is believed that when the opening of the pancreatic duct into the bile duct is abnormally high, it will cause the reflux of pancreatic juice into the bile duct causing bile duct epithelial malignancy. Other factors that may lead to malignancy include bile stagnation, stone formation and chronic inflammation in the cystic lumen. Although Schistosoma haematobium is mostly parasitized in intrahepatic bile ducts, it can also be parasitized in extrahepatic bile ducts. The worm itself and its metabolites can stimulate the bile duct mucosal epithelium for a long time and cause mucosal hyperplasia of bile ducts, resulting in tumor-like changes and carcinoma. 6.History of bile duct surgery Bile duct cancer can occur years after surgery and can occur in bile ducts without stones, mainly due to chronic bile duct infection leading to epithelial interstitial changes, often after bile duct internal drainage surgery. 7.Radioactive thorium dioxide In patients with a history of exposure to thorium, the age of onset of bile duct cancer is 10 years earlier than in those without a history of thorium exposure, and its average latency is 35 years (after exposure to thorium), and it occurs more often at the end of the intrahepatic biliary tree. 8. Sclerosing cholangitis malignant transformation Patients with primary sclerosing cholangitis (PSC) also have a higher chance of developing cholangiocarcinoma than the general population, and PSC is also associated with ulcerative colitis.