Cholangiocarcinoma (Bile Duct Cancer) Causes and Risk Factors

Cholangiocarcinoma is a rare and aggressive tumor that forms in the bile duct system, a series of thin tubes that transport bile from the liver to the gallbladder and small intestine. As food moves through the digestive tract, bile is released into the small intestine, where it aids digestion and facilitates the breakdown of fats.

Bile duct cancer is categorized based on its site of origin:

• Intrahepatic cholangiocarcinoma – Develops within the liver
• Perihilar cholangiocarcinoma – Develops in the area where the left and right hepatic ducts exit the liver and join to form the common hepatic duct
• Distal cholangiocarcinoma – Develops in the area where the bile ducts from the liver and gallbladder join to form the common bile duct, which passes through the pancreas and ends in the small intestine

Usually, cholangiocarcinoma arises in the cells that line the bile ducts. Symptoms can include abdominal pain and yellowing of the skin and whites of the eyes (jaundice).

What causes cholangiocarcinoma?

Bile duct cancer results from a harmful change to cellular DNA, which provides a “blueprint” for all aspects of cellular function. The mutation disrupts the normal processes of cell growth and death, causing the cell to multiply rapidly and survive longer than it should. Excess cells then build up, bind together and form a tumor.

Through extensive research, scientists have identified causal mutations in certain genes that normally suppress tumors (tumor suppressor genes) or promote orderly cell growth, division and viability (oncogenes). These include the:

• TP53 tumor suppressor gene
• KRAS oncogene
• HER2 oncogene
• MET oncogene

While cancer-related DNA mutations are sometimes present at birth, scientists have not linked many cases of cholangiocarcinoma to inherited DNA damage. Instead, the gene mutations associated with bile duct cancer are more likely to occur at random.

What are the risk factors for cholangiocarcinoma?

The known risk factors for bile duct cancer include both controllable and uncontrollable elements.

Cholangiocarcinoma risk factors that can be controlled

By making healthy lifestyle changes, it may be possible to control certain bile duct cancer risk factors, such as:

• Smoking – Tobacco use is a serious health risk that is definitively linked to many types of cancer, including cholangiocarcinoma.
• Obesity – Excess body weight is associated with many potentially serious health issues, including bile duct cancer.
• Poor liver health – Cirrhosis can result from long-term alcohol consumption or chronic hepatitis, increasing the risk of intrahepatic cholangiocarcinoma.
• Liver fluke infection – Harbored by raw and undercooked freshwater fish in certain parts of the world, liver flukes are parasites that can cause bile duct inflammation.

Cholangiocarcinoma risk factors that cannot be controlled

Some bile duct cancer risk factors cannot be controlled. These include:

• Advanced age – Cholangiocarcinoma is usually diagnosed after age 60.
• Genetics – A family history of bile duct cancer and certain inherited medical conditions, such as primary sclerosing cholangitis, choledochal cysts and familial adenomatous polyposis (FAP), are unmodifiable risk factors.
• Chronic bile duct inflammation – Bile duct stones, ulcerative colitis, Crohn’s disease, polycystic liver disease and Caroli syndrome can cause a backflow of digestive fluid that irritates and inflames the bile ducts.
• Prior exposure to Thorotrast (thorium dioxide) – Until the 1950s, this radioactive substance was routinely used as a contrast agent for X-rays.

Can cholangiocarcinoma be prevented?

Although bile duct cancer cannot be prevented, several strategies can help reduce the risk. These include:

• Drinking in moderation, if at all – Excessive consumption of alcoholic beverages can lead to cirrhosis, a known risk factor for bile duct cancer.
• Avoiding exposure to hazardous substances – Workers who may be exposed to toxins and carcinogens should use personal protective equipment (PPE) and adhere to all appropriate safety regulations.
• Taking travel precautions – When visiting areas where liver flukes are common, it is important to drink purified water and eat well-cooked food.
• Losing weight if necessary – Maintaining a healthy body weight can promote overall well-being and help protect against certain cancers, including cholangiocarcinoma.
• Quitting tobacco – Scientific evidence conclusively shows that cancer risk decreases with smoking cessation at any age.

Benefit from world-class care at Moffitt Cancer Center

Moffitt has received national recognition for its research breakthroughs and robust clinical trials program, both of which help us continually learn more about cholangiocarcinoma causes and risk factors. Taking a bench-to-bedside approach, we quickly incorporate our newly acquired knowledge into tangible prevention, diagnostic and treatment strategies for the benefit of our patients. For these reasons and many others, Moffitt was designated a Comprehensive Cancer Center by the National Cancer Institute.

If you would like to learn more about cholangiocarcinoma causes and risk factors, you can request an appointment with a specialist in our Gastrointestinal Oncology Program by calling 1-888-663-3488 or submitting a new patient registration form online. We do not require referrals.