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Risk factors for liver cancer
Any substance or condition that increases cancer risk is referred to as a risk factor. The most important risk factors for developing liver cancer are cirrhosis of the liver and infection with hepatitis B or C virus. However, most cancers are the result of many risk factors.
*Risk factors are generally listed in order from most significant to least significant. In most cases, it is impossible to rank the relative significance of individual risk factors with absolute certainty.
The incidence of liver cancer increases with age. More men than women develop liver cancer. Liver cancer is more common in countries with high rates of infection with hepatitis B and hepatitis C virus, such as some Asian countries (Mongolia, Korea, China, Japan and Thailand) and some African countries (Gambia, Mali, Guinea and Mozambique).
The following factors are known to increase the risk of developing liver cancer.
Cirrhosis is scarring of the liver. It occurs when scar tissue replaces the healthy tissue in the liver. The blood flow through the liver is blocked, and the liver can’t function normally. Cirrhosis can be caused by:
- infection with hepatitis B or C virus
- excessive use of alcohol over a long period of time
- metabolic disorders that cause liver damage
Regardless of the cause, cirrhosis of the liver increases the risk of hepatocellular carcinoma, the most common type of liver cancer.
Chronic infection with hepatitis B virus (HBV), hepatitis C virus (HCV) or both viruses increases the risk of developing liver cancer. Even if cirrhosis does not develop as a result of the infection, there is still an increased risk of liver cancer.
HBV can be spread from person to person through blood or other body fluids, such as semen or vaginal fluids. HCV is spread only through contact with infected blood.
HBV and HCV are spread through:
- blood transfusions
- The Canadian Blood Services tests every blood donation for both HBV and HCV. Only blood that passes these tests is used in Canada.
- unprotected sex with an infected person
- sharing drug needles or other drug equipment
- pregnancy or childbirth – from mother to child
- contaminated equipment used during
- body piercing
- dental or medical procedures
- workplace injuries involving needles or sharp equipment that has infected blood on it
- sharing personal care items, such as a razor or a toothbrush, with an infected person
Drinking 3 or more alcoholic drinks a day increases the risk of developing liver cancer. Alcohol can cause liver damage and lead to alcoholic cirrhosis.
People with HBV or HCV infection who drink alcohol every day are at greater risk of developing liver cancer than people who are infected with the virus but don't drink alcohol.
Smoking tobacco increases the risk of developing liver cancer. The risk increases with both the amount smoked and the length of time a person smokes.
Aflatoxin is a type of mycotoxin (a toxin produced by moulds and fungi). It can contaminate many different foods, including:
- cereal grains, such as corn, rice and wheat
- oilseeds, such as peanuts, soybeans and sunflowers
- spices, such as chilli peppers, black pepper and ginger
- tree nuts, such as almonds, walnuts, pistachios and brazil nuts
- food made from animals fed grain contaminated with aflatoxin
People who are exposed to aflatoxin are at an increased risk of developing liver cancer.
Aflatoxin can be a problem in countries with hot, damp climates and poor storage facilities. Aflatoxin exposure is greatest in Africa and Asia because of the high levels of contamination in food, stored grains, soil and water.
Aflatoxin is not a concern in Canada. The Canadian Food Inspection Agency monitors and tests nuts and nut products, as well as some dairy products, for aflatoxin contamination.
Thorium dioxide (Thorotrast) is a radioactive solution. It was used as a contrast mediumcontrast mediumA substance used in some diagnostic procedures to help parts of the body show up better on x-rays or other imaging tests. in the 1950s to improve x-ray examination of the blood system, nasal passages and sinus cavities. After injection, thorium dioxide collected in the liver, spleen and bone marrow.
People who have been exposed to thorium dioxide are at greater risk of developing angiosarcoma tumours, a rare type of liver cancer. Higher doses increase the risk, and the cancer may develop as many as 45 years after exposure.
Vinyl chloride is used in the plastics industry to produce polyvinyl chloride (PVC), which is used in many products. Occupational exposure to vinyl chloride increases the risk of developing both hepatocellular carcinoma and angiosarcoma tumours of the liver.
Hemochromatosis (iron overload) is a genetic disorder that causes the body to store higher than normal amounts of iron. The excess iron builds up in different tissues, especially the liver. When the liver stores too much iron, and the condition is not treated, the liver may be damaged.
People with untreated hemochromatosis are at an increased risk of liver cancer.
Women who take birth control pills for more than 5 years have a slightly higher risk of developing liver cancer.
People who have certain conditions that interfere with metabolismmetabolismThe chemical processes in the body that create and use energy. It includes breaking down food and transforming it into energy, eliminating wastes and toxins, breathing, circulating blood and regulating temperature. have an increased risk of developing liver cancer. These conditions may lead to cirrhosis of the liver or the growth of hepatic adenomas. Metabolic disorders that may increase the risk of liver cancer include:
- alpha-1 antitrypsin deficiency
- Too much alpha-1 antitrypsin protein is made and stored in the liver, which leads to liver damage and cirrhosis.
- People with this disorder do not make enough enzymes to remove the chemical porphyrin from the body.
- Porphyrin can build up in the liver, causing damage and cirrhosis.
- Studies have shown that some types of porphyria, such as porphyria cutanea tarda and acute intermittent porphyria, increase the risk of liver cancer.
- hereditary tyrosinemia
- People with hereditary tyrosinemia have high blood levels of the amino acid tyrosine and a shortage of an enzyme that breaks down tyrosine.
- If left untreated, tyrosine and its by-products build up in the liver, which can lead to liver failure and liver cancer.
- type I and III glycogen storage disease
- With glycogen storage disease (GSD), high amounts of glycogen (carbohydrate that is mainly stored in the liver and muscles) build up in the liver and other organs.
- If left untreated, type I GSD can lead to the growth of hepatic adenomas, which may develop into liver cancer in rare cases.
- If type III GSD is left untreated, it can lead to the growth of hepatic adenomas or cirrhosis, which may lead to lead to liver cancer.
Liver flukes are parasites that infect the liver. Opisthorchis viverrini (O. viverrini) is a type of liver fluke that is very common in Thailand, Laos, Vietnam, Cambodia and other countries in Southeast Asia. People become infected by eating raw fish that contains the eggs of the liver fluke.
Infection with O. viverrini increases the risk of developing cholangiocarcinoma, a rare type of cancer that starts in the bile ducts in the liver.
Primary sclerosing cholangitis is a disease in which the bile ducts in the liver become inflamed, scarred and narrowed. People with primary sclerosing cholangitis are at an increased risk of developing cholangiocarcinoma.
In non-alcoholic fatty liver disease (NAFLD), fat cells collect in the liver of people who do not drink large amounts of alcohol. The main risk factor for developing NAFLD is obesity. NAFLD is a condition which, by itself, does not cause any significant liver damage or increase the risk of liver cancer.
However, NAFLD can progress to non-alcoholic steatohepatitis (NASH). In NASH, the fatty tissue in the liver becomes inflamed and causes scar tissue to form. NASH may progress to liver damage and cirrhosis, which increases the risk of developing liver cancer.
Studies have shown that obesity is associated with an increased risk of liver cancer. This may be because NAFLD occurs in many people with obesity.
Workers who are known to have inhaled radioactive plutonium have an increased risk of developing liver cancer, especially angiosarcoma.
People with diabetes appear to have an increased risk of developing liver cancer. Studies have found that people with diabetes who develop liver cancer sometimes have other risk factors, such as heavy alcohol use, hepatitis infection, or both. Also, many people with diabetes tend to be overweight or obese, which may also increase their risk of liver cancer.
Possible risk factors
The following factors have some association with liver cancer, but there is not enough evidence to say they are known risk factors. Further study is needed to clarify the role of these factors for liver cancer.
- schistosomiasis – Schistosomiasis is an infection with a parasitic worm (Schistosoma haematobium). People can be infected when they swim in water that contains the worm. The larvae burrow into the skin and the worms move to other areas of the body such as the liver. The worms mature and can cause damage to the liver. Some studies have suggested that schistosomiasis may increase the risk of liver cancer, but the evidence is not yet conclusive.
- infection with Clonorchis sinensis (C. sinensis) – C. sinensis is a liver fluke that is common in Southeast Asia. Studies have suggested that C. sinensis infection may increase the risk of cholangiocarcinoma.
- arsenic – Some studies have shown that the rate of liver cancer is higher in areas where there are high levels of arsenic in the drinking water, but many of these areas also have high rates of hepatitis B infection. More study is needed to find out if arsenic exposure increases a person’s risk for liver cancer.
- exposure to trichloroethylene – Trichloroethylene (TCE) is a solvent used to remove grease from metal. It may be used as a solvent in dry cleaning. Some studies have suggested that exposure to TCE may increase the risk of developing liver cancer.
- exposure to polychlorinated biphenyls – Some studies of workers exposed to polychlorinated biphenyls (PCBs) have shown a link between PCBs and a higher risk of liver cancer.
- betel quid – Betel quid (also called betel nut) is areca nut and lime wrapped in a betel leaf (called paan). Chewing betel quid is a common practice in Southeast Asia. Some studies have shown that people who chew betel quid have a higher risk of liver cancer.
Unknown risk factors
The following are factors for which there is not enough evidence or the evidence is inconclusive. In other words, it can’t be determined for sure whether these risk factors are or are not associated with liver cancer.
- anabolic steroids