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 one risk factor, or even many, 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. Knowing your risk factors and talking about them with your doctor might help you make more informed lifestyle and health care choices.

Medical conditions that increase the risk of gallbladder cancer 

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. Gallstones are very common, and gallbladder cancer is quite rare, especially in the US. Most people with gallstones never develop gallbladder cancer.

Porcelain gallbladder

In porcelain gallbladder the wall of the gallbladder becomes covered with calcium deposits. It sometimes occurs after the gallbladder has been inflamed a long time, 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.

Biliary cysts

Biliary cysts, formerly called choledochal cysts, are bile-filled sacs that form along the bile ducts, especially the common bile duct. The common bile duct is the tube that carries bile from the liver and gallbladder to the small intestine. These cysts are present at birth. They can grow large over time and might 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.

Abnormality of the pancreaticobiliary duct junction

The pancreas releases fluids through the pancreatic duct into the small intestine to help digestion. The pancreatic duct normally joins the common bile duct (tube that carries bile from the liver and gallbladder) as it enters the small intestine, just before the Sphincter of Oddi.  Sometimes, these 2 ducts (pancreatic and common bile) join further away from the Sphincter of Oddi, and form an abnormal pancreaticobiliary duct junction.

When this happens, juice from the pancreatic duct can flow backward (reflux) into the bile ducts. This backward flow can also keep bile from flowing out of the bile ducts as quickly as it should. People with this abnormal duct junction are at higher risk of gallbladder cancer. Scientists are not sure if the increased risk is from damage caused by the pancreatic juice or from bile being unable to flow quickly through the ducts, causing the bile itself to damage the ducts.

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. Some form when small gallstones get embedded 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 polyps that size or larger.

Primary sclerosing cholangitis

In primary sclerosing cholangitis (PSC), inflammation of the bile ducts (cholangitis) forms 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.

Infections

People chronically infected with salmonella (the bacterium that causes typhoid) and Helicobacter (H. pylori) 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.

Other possible risk factors for gallbladder cancer

Female sex

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

Excess body weight or obesity

Patients with gallbladder cancer are more likely to have excess body weight (or obesity) than people without this disease. Obesity is also a risk factor for gallstones, which might help explain this link.

Being older

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

Exposure to toxins

Studies have found that being exposed to certain toxins might increase a person’s risk for gallbladder cancer. These toxins include chemicals used in cigarettes, radon, and possibly aflatoxin. Workers in the rubber and textile industries also have an increased risk of developing gallbladder cancer. Further research is needed to understand these associations better.