Causes of gallbladder cancer

By Dr Ananya Mandal, MD

Gallbladder cancer is a rare cancer in the European countries. Around 640 to 670 new cases are diagnosed each year.

Gallbladder cancer is more common in women than in men. About 7 out of every 10 cases diagnosed are in women. In addition, they are commonly seen in individuals over the age of 70 and are rare in people below 50.

Most of the gallbladder cancers are adenocarcinoma where the cancer begins in the inner lining of the gall bladder. The exact cause of gallbladder cancer is unknown but there are certain risk factors that raise the risk of gallbladder cancer.

Different cancers have different risk factors. Those with the risk factors do not mean that they will definitely get the cancer.

Risk factors of gallbladder cancer

Risk factors that predispose to gallbladder cancer include old age, sex of the patient, cholecystitis and so forth.

Age of the patient

Most of the gallbladder cancers affect elderly people and the cancer is rare under the age of 70 in the UK.

Sex of the patient

Gallbladder disease as such is more common in women. Similarly gallbladder cancer affects women more commonly than men.

Cholecystitis

Gallstones and inflammation of the gallbladder is also known as cholecystitis. This is by far the most common risk factor that predisposes to gallbladder cancer.

Gallstones are hard stones that are formed within the gallbladder due to deposition of cholesterol and minerals from bile.

About 8 out of 10 people with gallbladder cancer (80%) have gallstones or an inflamed gallbladder at diagnosis. However, most people with an inflamed gallbladder or gallstones do not get gallbladder cancer.

Family history of gallstones and gallbladder cancer

Those with someone in the family (a first degree relative like a parent or a sibling) with gallstones have a double the chance of gallbladder cancer.

In addition, those with a family history of gallstones who also have gallstones themselves have almost 60 times the normal risk of gallbladder cancer.

Those with a first degree relative with gallbladder cancer are five times more likely to develop gallbladder cancer than people who do not have a relative with it. The risk, however, still remains very small as the cancer is rare.

The genetic mutation BRCA2 that leads to increased risk of breast and ovarian cancer also slightly increases the risk of gallbladder and bile duct cancer.

Genetics

Some races and ethnicities are more at risk of gall bladder cancer than others. The basis could be genetics. For example, north India has the highest rate of gallbladder cancer in the world. Other countries with significantly high rates are Israel, Chile, Ecuador, Bolivia, Mexico, Korea, Japan and Pakistan.

Among Americans black and Hispanic population as well as Native Americans in south-western USA have a greater incidence of gallbladder cancer than the white population. Lower rates are found in Singapore and Nigeria.

Smokers and exposure to chemicals

Cigarettes and some industrial chemicals containing nitrosamines can damage the DNA and lead to genetic mutations and raise the risk of gallbladder and other cancers. Workers in the metal or rubber industry are more likely to develop gallbladder cancer.

Porcelain gallbladder

This is a condition where calcium deposits build up on the inside wall of the gallbladder hardening the walls. This is usually seen in individuals who have repeated cholecystitis or inflammation of the gallbladder.

Primary sclerosing cholangitis

This is a form of inflammation of the bile ducts. This also raises the risk of gallbladder cancer.

Defects of the pancreas and bile ducts

Defects of the pancreas and bile ducts raise the gallbladder cancer risk. Abnormalities in the connection between the bile duct and the pancreas, outgrowths in the bile duct (choledochal cysts) may also be risk factors for gall bladder cancer. These conditions may affect a baby since birth but symptoms may appear much later.

Galbladder polyps

These are non-cancerous growths within the gallbladder. They develop on the surface lining of the gallbladder. Over a long time these may develop into cancers. Polyps over 1 centimetre (10mm) usually need surgical removal of the gallbladder to prevent cancer.

Obesity and overweight

Being obese or overweight raises the risk of gallstones and cholecystitis. This is mainly because they change the hormonal balances of the body particularly for women. Studies show that more than one in ten cases of gallbladder cancer in men and almost a third of cases in women are due to being overweight.

Diet

Diet high in carbohydrates and low in fibre may increase the risk of gallbladder cancer. Diet rich in fresh fruit and vegetables seems to reduce the risk of many cancers, including gallbladder cancer. Inclusion of vitamins A, C and E and antioxidant chemicals in diet is also important for cancer prevention.

Diabetes

Diabetes may also raise the risk of gallbladder cancer.

Typhoid causing Salmonella infection

Typhoid causing Salmonella infection can increase the risk of gallbladder cancer in people who have gallstones. This is seen commonly in Chile and North India. Helicobacter pylori - bacteria responsible for peptic ulcers, may also raise risk of gallbladder cancers.

Exposure to female hormones in hormone replacement therapy

Women who have increased exposure to the hormone oestrogen may have an increased risk of gallbladder cancer. With longer use of Hormone replacement therapy the risk of gallbladder cancer seems to rise.

Reviewed by April Cashin-Garbutt, BA Hons (Cantab)

Further Reading

Sources

  1. http://cancerhelp.cancerresearchuk.org/type/gallbladder-cancer/about/risks-and-causes-of-gallbladder-cancer
  2. http://www.macmillan.org.uk/Cancerinformation/Cancertypes/Gallbladder/Gallbladdercancer.aspx
  3. http://www.liverandpancreascancer.com/docs/galbladder%20cancer.pdf
  4. http://www.cancer.org/acs/groups/cid/documents/webcontent/003101-pdf.pdf
  5. http://www.cinj.org/documents/Gallbladdercancer.pdf
  6. http://www.orpha.net/data/patho/Pro/en/CarcinomaGallbladder-FRenPro10765.pdf

Last Updated: Jul 24, 2013

Comments
  1. Mukul Das Mukul Das India says:

    Edible oil adulterants, argemone oil and butter yellow,
    as aetiological factors for gall bladder cancer
    EUROPEAN JOURNAL OF CANCER 4 8 ( 2 0 1 2 ) 2 0 7 5 –2 0 8 5

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