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We don’t know the exact cause of most bile duct cancers, but we do know some of the risk factors that make a person more likely to develop these cancers.

There seems to be a link between bile duct cancer and things that irritate and inflame the bile ducts, whether it’s bile duct stones, infection with a parasite, or something else.

Scientists are starting to understand how inflammation might lead to certain changes in the DNA of cells, making them grow out of control and form cancers. DNA is the chemical in each of our cells that makes up our genes (the instructions for how our cells function).

• Genes that control when cells grow, divide into new cells, and die are called oncogenes.
• Genes that slow down cell division or cause cells to die at the right time are called tumor suppressor genes.

Cancers can be caused by DNA changes (mutations) that turn on oncogenes or turn off tumor suppressor genes. Changes in many different genes are usually needed for a cell to become cancer.

We usually look like our parents because they are the source of our DNA. But DNA affects more than how we look. Some people inherit DNA mutations from their parents that greatly increase their risk for certain cancers.

There are few known genetically inherited disorders that are associated with higher risk for bile duct cancer. Gene mutations related to bile duct cancers are usually acquired during life rather than inherited. For example, acquired changes in the TP53 tumor suppressor gene are found in most bile duct cancers. Other genes that may play a role in bile duct cancers include KRAS, HER2, and ALK.

Some of the gene changes that lead to bile duct cancer might be caused by inflammation. But sometimes the cause of these changes is not known. Many gene changes might just be random events that sometimes happen inside a cell, without having an outside cause.