What Causes Gallbladder Cancer?

Researchers have found some risk factors that make a person more likely to develop gallbladder cancer. (See Risk Factors for Gallbladder Cancer.) They're also learning more about how some of these risk factors might lead to gallbladder cancer.

Chronic gallbladder inflammation is a common link among many of the risk factors for 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, defects in the ducts that carry fluids from the gallbladder and pancreas to the small intestine might allow 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, which might increase the risk of gallbladder cancer.

Scientists are starting to understand how risk factors like 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. We usually look like our parents because they are the source of our DNA. But DNA affects more than how we look.

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

Cancer 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.

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, and PIK3CA. Some of the gene changes that lead to gallbladder cancer might be caused by chronic 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.