Do we know what causes gallbladder cancer?
Researchers have found several risk factors that make a person more likely to develop gallbladder cancer. (See the previous section, “What are the risk factors for gallbladder cancer?”) They are also beginning to understand how some of these risk factors may lead to gallbladder cancer.
Most doctors studying the subject think that chronic inflammation is the major cause of gallbladder cancer. For example, when someone has gallstones, the gallbladder may release bile more slowly. This means that cells in the gallbladder are exposed to the chemicals in bile for longer than usual. This could lead to irritation and inflammation.
In another example, 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 (reflux) into the gallbladder and bile ducts. This reflux of pancreatic juices might inflame and stimulate growth of the cells lining the gallbladder and bile ducts. This might increase the risk of gallbladder cancer.
Scientists have begun to understand how risk factors such as inflammation may lead to certain changes in the DNA of cells, making them 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. Changes in several different genes are usually needed for a cell to become cancerous.
Some people inherit DNA mutations from their parents that greatly increase their risk for certain cancers. But inherited gene mutations are not thought 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 TP53 tumor suppressor gene are found in many cases of gallbladder cancer. Other genes that may play a role in gallbladder cancers include KRAS, BRAF, CDKN2, and HER2.
Many newer cancer drugs target cells with specific gene changes. Knowing which genes are abnormal in gallbladder cancer cells could help doctors determine which of these new drugs might be effective.
Last Medical Review: 06/12/2013
Last Revised: 02/06/2014