Gallbladder Cancer Overview

Gallbladder Cancer - Causes and Risk Factors

Gallbladder cancer is strongly linked to chronic gallbladder inflammation. Gallstones, the most common cause of this inflammation, expose the gallbladder lining to bile chemicals for prolonged periods, potentially triggering abnormal cell growth and mutations. The most common type of gallbladder cancer is adenocarcinoma of the gallbladder, which begins in the glandular cells lining the organ.

Another contributing factor is biliary reflux, where pancreatic juices flow backward into the gallbladder, causing irritation that may promote cancerous changes in the cells lining the bile ducts.

At the genetic level, gallbladder cancer often involves acquired DNA mutations, rather than inherited ones. These mutations can turn normal cells cancerous by activating oncogenes or disabling tumour suppressor genes. Key genetic changes linked to gallbladder cancer include:

TP53 mutations, which impair the body's ability to control cell growth.
KRAS, BRAF and PIK3CA mutations, which drive uncontrolled cell division.

Most of these mutations are thought to arise from prolonged inflammation rather than hereditary factors.

What are the risk factors for gallbladder cancer?

Several factors may increase the risk of gallbladder cancer, including:

Gallstones: The most common risk factor, as chronic irritation from gallstones can lead to inflammation and abnormal cell growth. Up to four out of five people with gallbladder cancer have gallstones when they are diagnosed.
Chronic gallbladder inflammation: Conditions such as porcelain gallbladder (calcification of the gallbladder wall) increase the risk of malignant transformation.
Older age: Most cases occur in individuals over 65 years old, though younger individuals with certain risk factors may also develop the disease. The average age at diagnosis is 72 years.
Sex: Women are more likely than men to develop gallbladder cancer, possibly due to hormonal influences on gallstone formation.
Obesity: Excess body weight increases cholesterol levels in bile, promoting gallstone formation and inflammation.
Certain infections: Chronic infections with bacteria such as Salmonella have been associated with a higher risk of gallbladder cancer.
Family history: A history of gallbladder cancer in close relatives may increase genetic susceptibility.
Abnormalities of the bile ducts: Conditions such as congenital bile duct cysts can predispose individuals to gallbladder cancer.
Smoking and occupational exposure: Smoking and long-term exposure to industrial chemicals, particularly in the textile, rubber and mining industries, might increase the risk of gallbladder cancer.