Gallbladder cancer is commonly observed in Central and South America and is also observed in Native American Indians and Hispanics. Though the causes of gallbladder cannot be pinpointed, a few ‘risk factors’ have been elicit. Learn about them in this article.
In the human body, the gallbladder is sandwiched between the liver and the duodenum. The gallbladder is a small organ that plays a role in the metabolism of fat in the body. When food containing fat is consumed, a hormone cholecystokinin is secreted in the body. This cholecystokinin then stimulates the gallbladder to release its contents into the duodenum. Gallbladder functions in the concentration of bile produced by the liver. This bile, when released in the duodenum, emulsifies partially digested fat.
Gallbladder is found in most vertebrates but is absent in invertebrates. The removal of gallbladder does not affect survival of the organism, as no crucial functions are impaired. Gallbladder cancer is one of the rare cancers that plague human beings. This disease is peculiar in its geographical distribution as well as racial distribution – it is found commonly in South America, Japan, Central and Eastern Europe, South Asia, also it is commonly seen in Native American Indians and Hispanics. This could probably provide some clues about the possible risk factors and causes of gallbladder cancer, but no such trend has been yet elicit.
Causative Factors for Gallbladder Cancer
As like any other cancer, gallbladder cancer is caused by mutations in the gallbladder cell. In the human body, each cell has something known as tumor suppressor genes. A tumor suppressor gene prevents cells from becoming cancerous. Take the example p53. p53 is a tumor suppressor protein encoded by the gene TP53 gene. The main function of p53 is to arrest the cell cycle if the DNA in the cell has been damaged. If however, there is a mutation in the p53 encoding gene, the cell will continue to replicate in spite of any DNA damage. To add to this, if the DNA damage is such that it makes the cell cancerous, it will lead to growth and proliferation of a cancer cell, leading to tumor.
Apart from oncogenes, mutations in tumor suppressor genes are one of the major causes of many types of cancer, especially gallbladder cancer. Typical tumor suppressor genes and oncogenes related to gallbladder carcinoma include BRAF, KRAS, HER2, FHIT and CDKN2. A carcinogen is a substance that induces cancerous mutations in the cell. The exact manner in which a carcinogen acts need not always be evident. Different carcinogens act in different ways. At the same time, certain conditions can also prove to be ‘carcinogenic’; they make a person more susceptible to develop cancer. In case of gallbladder cancer, the exact causes are unknown, but several conditions have been elicit to increase the risk of developing this cancer.
Risk Factors
Primary cancer arises in the connective tissue present between the different layers of the gallbladder wall. From here the cancer spreads to the gallbladder, the liver and then other parts of the body. The risk factors enlisted below have been shown to increase susceptibility to gallbladder cancer.
Gallstones
Gallstones (or cholelithiasis) is a condition in which stone-like deposits of either cholesterol or bilirubin collect in the gallbladder. Many causes of gallstones have been indicated; these include diabetes, liver cirrhosis, rapid weight loss induced by following a very low-calorie diet also causes gallstones, chronic hemolytic anemia etc. In general women are twice more prone to gallstones than men (menopausal women even more).
The direct connection between gallstones and cancer cannot be yet laid down. However, exposure to hepatocarcinogens along with a gallstones-inducing diet made more than 50% test animals develop gallbladder cancer. Even in humans, around 70 to 90% patients suffering from cancer of the gallbladder have been detected with the presence of gallstones as well.
Cholecystitis
Formation of gallstones in the gallbladder can lead to a painful condition called cholecystitis. Cholecystitis is marked by severe inflammation of the gallbladder. If neglected, the inflammation can progress to severe necrosis. This in turn can lead to a secondary infection by the normal gut microflora, such as Escherichia coli and Bacteroides. The other end of the spectrum is if the inflammation remains a low-level chronic type of inflammation. This condition is known as chronic cholecystitis and is characterized by a fibrotic and calcified gallbladder.
Porcelain Gallbladder
Porcelain gallbladder is the medical condition in which there is heavy calcification in the gallbladder. This condition can be regarded as the last stage of gallstones, or the most progressed version of gallstones. If the gallstones formed in the gallbladder are not removed and are allowed to accumulate, it may lead to calcification of the stones. Porcelain gallbladder is a rare condition in itself, but it has been shown to be linked to gallbladder cancer.
According to a study conducted by Stephen and Berger at the Massachusetts General Hospital, Boston, “the incidence of cancer depends on the pattern of calcification“. In general, obese female patients over the age of 40 are at a greater risk of developing porcelain gallbladder, and are hence at a greater risk of developing cancer as well.
Environmental Factors
Every disease has certain factors that cannot be controlled. These are factors that increase the risk of certain individuals developing a particular disease. They include traits like gender, age, lifestyle or race. With respect to gallbladder cancer, peculiar observations have been made. It has been seen that gallbladder is twice more common in women than in men. It is also more likely to occur in individuals who are 40 years or older (particularly the age group of 50 to 60 years). In terms of lifestyle, this carcinoma has been observed more commonly in obese individuals. Obesity is a major cause of concern in most developed countries, including the US.
As with many other cancers, the exact causes of gallbladder cancer remain a mystery. However, the above factors are known to be linked with gallbladder cancer. Since early diagnosis of the disease is not possible, it is advisable that you get a check up done if you fall under any of the predisposed groups as discussed above. One of the surest way to eliminate the risk of developing cancer is to remove gallstones. Treatment most often includes cholecystectomy (surgical removal of the gallbladder). However, as mentioned earlier, cholecystectomy does not impair any major functions of the body, and persons can live a long life after surgery.
