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Cancers that begin in the lining of the gallbladder are called gallbladder cancer. This cancer is rare in the United States; fewer than 5,000 cases are diagnosed in this country each year. Women are about three times more likely than men to develop this type of cancer. This is thought to be related to a hormone, estrogen, which can lead to gallstones. Obesity has been shown to be a risk factor for gallbladder cancer in many studies, perhaps because obesity is also a risk factor for gallstones.
Gallstones are present in over three quarters of patients with gallbladder cancer. However only about 0.5-3% of individuals who who have gallstones, develop gallbladder cancer. Some gallbladder cancers are “incidentally found” when the gallbladder is removed due to gallstones. Cancers are found at an earlier stage and more likely to be cured.
High rates of gallstones are found in certain populations. For instance, the Pima Indians in Arizona often develop gallstones at an early age, and have high rates of gallbladder cancer. Similarly, the Areucanian and Mapuche Indians who live in Chile and people in Northern India and Pakistan also have a high likelihood of getting gallstones. These regions have some of the highest rates of gallbladder cancer in the world. The reasons some people develop gallbladder cancer and some do not ("carcinogenesis") are far from being understood.
Cancers that develop in the bile ducts are known as cholangiocarcinomas. Overall, these cancers are slightly more common in men than in women.
Cholangiocarcinomas can be located in the bile ducts inside the liver (“intrahepatic”), or in ducts outside of the liver (“extrahepatic”). Several studies suggest an association between cholangiocarcinomas and infection with certain types of liver parasites, particularly in Thailand. Eating undercooked fish can lead to ingestion of these parasites (especially one called Opisthorcis viverrini) which can then lay eggs in the human host’s biliary system. The flukes can cause mechanical irritation as well as giving off chemicals which can promote cancer.
In the West, a common cause of cholangiocarcinoma is primary sclerosing cholangitis, or “PSC.” This is an inflammatory condition thought to be related to abnormalities in the immune system which can cause blockages within bile ducts within the liver. Up to 40% of patients with this inflammatory disorder can develop cholangiocarcinoma, and cancers in these patients tend to present at a young age, typically between 30 and 50. Patients with PSC also have up to a 90% chance of having ulcerative colitis, an inflammatory disease which affects the colon. This can also increase their risk for colon cancer.
Other rarer causes of cholangiocarcinomas include genetic disorders, including some associated with other cancers like colon cancer, and diseases which cause cysts to develop in the liver. Underlying scarring of the liver, or cirrhosis, can also lead to a 10-fold higher risk of cholangiocarcinoma compared with the general population. The incidence of cholangiocarcinoma associated with cirrhosis is rising in the United States.
Staging of cholangiocarcinoma will help make decisions about what treatments are possible and help predict the potential for survival. It tells where the cancer is and if it invades any major structures. It also helps doctors compare results from treatment choices used in different studies.
Primary cancer of the liver cells (not the bile duct cells) is called hepatocellular carcinoma, HCC, or hepatoma. HCC makes up 80-90% of all primary liver cancers, and is the fifth most common cancer worldwide. It is also the most rapidly increasing cause of cancer in the United States.
Infection with hepatitis viruses is a major risk factor for the development of HCC. In Asia and Africa, Hepatitis B is very common, and this infection leads to about 80% of all HCC cases worldwide. Hepatitis B can lead to cancer without the development of scarring in the liver (cirrhosis). There is now a vaccine available for hepatitis B, and several studies looking at vaccinating children against hepatitis B are showing progress in preventing HCC. Because many individuals in Asia and Africa are infected with hepatitis B as young children or infants, their tumors often develop at younger ages.
In western countries, about 80% of patients with HCC have underlying liver cirrhosis. The main reasons for this are underlying hepatitis C, heavy alcohol consumption, and the “metabolic syndrome.” Metabolic syndrome includes diabetes, obesity, and hypertension which can lead to fatty changes in the liver. These fatty change in the liver, called NAFLD (“non-alcoholic fatty liver disease”) can progress to liver inflammation called “NASH” (“non-alcoholic steatohepatitis”), which can lead to liver cancer in some people.
Less common causes of HCC include certain genetic disorders like hemochromatosis and alpha-1-antitrypsin deficiency. Autoimmune hepatitis and some toxins like aflatoxin (a mold which grows on corn and peanuts) also can lead to HCC. Steroids and hormone replacement may also be associated with some types of liver cancers.
Other than alcohol and aflatoxin, little is known about the role of diet in contributing to HCC. The role of coffee consumption has received attention recently because several studies have reported that those who drink 2-4 cups of coffee per day may have a lower risk of HCC. This may be because coffee drinkers tend to have lower insulin levels, and less adult-onset diabetes.
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