Risk Factors for Gallbladder Cancer

Scientists have found some risk factors that make a person more likely to develop gallbladder cancer. Many of these are related in some way to chronic inflammation (long-lasting irritation and swelling) in the gallbladder.

What is a risk factor?

A risk factor is anything that affects your chance of getting a disease such as cancer. Different cancers have different risk factors. Some risk factors, like smoking, can be changed. Others, like a person’s age or family history, can’t be changed.

But having a risk factor, or even many risk factors, doesn't mean that a person will get the disease. And many people who get the disease may have few or no known risk factors.

Gallstones

Gallstones are the most common risk factor for gallbladder cancer. Gallstones are pebble-like collections of cholesterol and other substances that form in the gallbladder and can cause chronic inflammation. Up to 4 out of 5 people with gallbladder cancer have gallstones when they're diagnosed. But gallstones are very common, and gallbladder cancer is quite rare, especially in the US. And most people with gallstones never develop gallbladder cancer.

Porcelain gallbladder

Porcelain gallbladder is a condition in which the wall of the gallbladder becomes covered with calcium deposits. It sometimes occurs after long-term inflammation of the gallbladder (cholecystitis), which can be caused by gallstones. People with this condition have a higher risk of developing gallbladder cancer, possibly because both conditions can be related to inflammation.

Sex

In the US, gallbladder cancer occurs 3 to 4 times more often in women than in men. Gallstones and gallbladder inflammation are important risk factors for gallbladder cancer and are also much more common in women than men.

Obesity

Patients with gallbladder cancer are more often overweight or obese than people without this disease. Obesity is also a risk factor for gallstones, which might help explain this link.

Older age

Gallbladder cancer is seen mainly in older people, but younger people can develop it as well. The average age of people when they are diagnosed is 72. Most people with gallbladder cancer are 65 or older when it's found.

Ethnicity and geography

In the US, the risk of developing gallbladder cancer is highest among Mexican and Latin Americans and Native Americans. They are also more likely to have gallstones than members of other ethnic and racial groups. The risk is lowest among African Americans. Worldwide, gallbladder cancer is much more common in India, Pakistan, and Central European and South American countries than it is in the US.

Choledochal cysts

Choledochal cysts are bile-filled sacs along the common bile duct, the tube that carries bile from the liver and gallbladder to the small intestine. (Choledochal means having to do with the common bile duct.) The cysts can grow large over time and may contain as much as 1 to 2 quarts of bile. The cells lining the sac often have areas of pre-cancerous changes, which can progress to gallbladder cancer over time.

Abnormalities of the bile ducts

The pancreas is another organ that releases fluids through a duct into the small intestine to help digestion. This duct normally meets up with the common bile duct just as it enters the small intestine. Some people have a defect where these ducts meet that lets juice from the pancreas flow backward (reflux) into the bile ducts. This backward flow also keeps bile from flowing out of the bile ducts as quickly as it should. People with these abnormalities are at higher risk of gallbladder cancer. Scientists are not sure if the increased risk is due to damage caused by the pancreatic juice or is due to the bile that can't quickly flow through the ducts causing them to be damaged by substances in the bile itself.

Gallbladder polyps

A gallbladder polyp is a growth that bulges from the surface of the inner gallbladder wall. Some polyps are formed by cholesterol deposits in the gallbladder wall. Others may be small tumors (either cancer or not cancer) or may be caused by inflammation. Polyps larger than 1 centimeter (almost a half inch) are more likely to be cancer, so doctors often recommend removing the gallbladder in patients with gallbladder polyps that size or larger.

Primary sclerosing cholangitis

Primary sclerosing cholangitis (PSC) is a condition in which inflammation of the bile ducts (cholangitis) leads to the formation of scar tissue (sclerosis). People with PSC have an increased risk of gallbladder and bile duct cancer. The cause of the inflammation is not usually known. Many people with PSC also have ulcerative colitis, a type of inflammatory bowel disease.

Typhoid

People chronically infected with salmonella (the bacterium that causes typhoid) and those who are carriers of typhoid are more likely to get gallbladder cancer than those not infected. This is probably because the infection can cause gallbladder inflammation. Typhoid is very rare in the US.

Family history

Most gallbladder cancers are not found in people with a family history of the disease. A history of gallbladder cancer in the family seems to increase a person’s chances of developing this cancer, but the risk is still low because this is a rare disease.

Other possible risk factors

Studies have found other factors that might increase the risk of gallbladder cancer, but the links are not as clear. These include:

• Smoking
• Exposure to chemicals used in the rubber and textile industries
• Exposure to nitrosamines