Researchers have found several risk factors that make a person more likely to develop gallbladder cancer (see the section, "What are the risk factors for gallbladder cancer?"). They are also making progress in understanding how some of these risk factors lead to gallbladder cancer.

Most doctors studying the subject think that chronic inflammation is the major cause of gallbladder cancer. When gallstones are present, the gallbladder may release bile more slowly. This means that gallbladder tissue is exposed to the bile for longer than usual. This may lead to irritation and inflammation. Scientists also suspect that this longer exposure to possible cancer-causing substances in the bile could also be responsible. Certain abnormalities in the ducts that carry fluids from the gallbladder and pancreas to the small intestine can cause juices from the pancreas to flow backward into the gallbladder and bile ducts. Researchers suspect that this reflux (backward flow) of pancreatic juices may irritate the cells lining the gallbladder and bile ducts in a way that causes irritation and inflammation. This may stimulate their growth and perhaps make them more sensitive to cancer-causing substances.

Scientists have begun to understand how risk factors such as 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 look like 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 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 gallbladder cancers.

Gene mutations related to gallbladder 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 gallbladder cancer. Other genes that may play a role in gallbladder cancers include k-ras, b-RAF, FHIT, CDKN2, and HER2.

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

Last Medical Review: 11/02/2009
Last Revised: 11/02/2009