Is bile duct cancer also caused by genetic factors?

Is bile duct cancer also caused by genetic factors? I believe that patients and their families are very concerned about this issue. After all, bile duct cancer is also a very serious cancer. If patients suffer from bile duct cancer, they are more afraid that they will hurt their relatives, especially their children. So, is bile duct cancer also caused by genetic factors? Let us understand it through the causes of bile duct cancer.

Causes of bile duct cancer:

1. Chronic inflammation and infection of the bile duct: Long-term chronic inflammation is the basis for the occurrence of bile duct cancer, because clinically found that diseases related to bile duct cancer can lead to chronic inflammation of the bile duct. Certain substances in the bile (such as metabolites of bile acid) stimulate the bile duct mucosa for a long time, leading to atypical epithelial hyperplasia.

2. Bile duct and gallbladder stones: Forty percent of bile duct cancer patients have gallstones, so it is believed that chronic stimulation from 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 in the general population. The age of onset of bile duct cancer patients with ulcerative colitis is 20 to 30 years earlier than that of the general population, with an average age of 40 to 45 years. They often have a long history of colitis. Chronic bacteremia in the portal vein system of patients may be the cause of bile duct cancer and PSC. The lesions often affect the entire colon. Ulcerative colitis-induced bile duct cancer may be related to chronic portal vein bacteremia.

4. History of biliary surgery: Cholangiocarcinoma may occur many years after surgery and may occur in bile ducts that do not contain stones. It is mainly caused by chronic biliary infection leading to epithelial anaplasia, often after internal biliary drainage.

5. Among patients with a history of contact with radioactive thorium dioxide and thorium, the onset age of cholangiocarcinoma is 10 years earlier than those with no history of thorium exposure. The average incubation period is 35 years (after exposure to thorium), and it mostly occurs at the distal end of the intrahepatic bile duct tree.

6. Cystic malformation of the bile duct (congenital bile duct dilatation) It has become a consensus that congenital bile duct cysts are prone to cancer. The incidence of bile duct cancer in patients with congenital bile duct cysts is as high as 20 to 30 percent, and patients with bile duct cysts develop cancer 20 to 30 years earlier than normal people. Although 75 percent of bile duct cysts show symptoms in infancy and childhood, as far as the occurrence of bile duct cancer is concerned, 3/4 of patients have symptoms of bile duct cysts in adulthood. Regarding the mechanism of bile duct cysts leading to bile duct cancer, some people believe that when the opening of the pancreatic duct into the bile duct is abnormally high, pancreatic fluid will flow back into the bile duct, causing malignant changes in the bile duct epithelium. Other factors that may lead to malignant changes include bile stasis, stone formation, and chronic inflammation in the cyst cavity.

7. Infection with liver fluke (Clorchis sinensis) Infection with Clonorchis sinensis is also believed to be related to the occurrence of cholangiocarcinoma. Although Clonorchis sinensis mostly parasitizes in the intrahepatic bile duct, it can also parasitize in the extrahepatic bile duct. The worm itself and its metabolic products cause long-term stimulation to the bile duct mucosal epithelium, causing hyperplasia of the bile duct mucosa, tumor-like changes, and canceration.

8. Malignant transformation of sclerosing cholangitis: Patients with primary sclerosing cholangitis (PSC) have a higher chance of developing bile duct cancer than the general population. PSC is also related to ulcerative colitis.

9. Hepatitis B virus infection Some domestic bile duct cancer patients are also infected with hepatitis B virus. Whether there is a connection between the two remains to be further clarified.

10. K-ras gene mutation: Molecular biological studies in recent years have shown that the mutation rate of codon 12 of the K-ras gene in cholangiocarcinoma is as high as 80%, indicating that the K-ras gene mutation may play a relatively important role in the occurrence of cholangiocarcinoma.

In addition, it may be related to pancreatic juice reflux, bile stasis, stone formation, malignant transformation of benign bile duct tumors, and tumor-like differentiation of liver stem cells, all of which can cause chronic inflammatory stimulation of the bile duct mucosa and induce bile duct cancer.