While we do not know the exact cause of most bile duct cancers, researchers have found several risk factors that make a person more likely to develop bile duct cancer (see the section, "What are the risk factors for bile duct cancer?"). There seems to be a link between this cancer and things that irritate and inflame the bile duct, whether it's bile duct stones or infestation with a parasite.

Scientists have begun to understand how inflammation may lead to certain changes in the DNA of cells, causing them to grow abnormally and form cancers. DNA is the chemical in each of our cells that makes up our genes -- the instructions for how our cells function. We usually resemble our parents because they are the source of our DNA. However, DNA affects more than how we look.

Some genes contain instructions for controlling when cells grow and divide. Genes that promote cell division or keep cells alive longer than normal 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.

Some people inherit DNA mutations from their parents that greatly increase their risk for certain cancers. But inherited gene mutations are not believed to cause very many bile duct cancers.

Gene mutations related to bile duct cancers are usually acquired during life rather than being inherited. For example, acquired changes in the p53 tumor suppressor gene are found in most cases of bile duct cancer. Other genes that may play a role in bile duct cancers include K-ras, HER2/neu, and c-met.

Many newer cancer drugs target cells with specific gene changes. Knowing which genes are abnormal in bile duct cancer cells may help doctors find out which of these new drugs might be effective.