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Although several risk factors for liver cancer are known (see Liver Cancer Risk Factors), exactly how these might lead normal liver cells to become cancer is only partly understood. Some of these risk factors affect the DNA of cells in the liver, which can result in abnormal cell growth and may cause cancers to form.

DNA is the chemical in our cells that carries our genes, which control how our cells function. We look like our parents because they are the source of our DNA. But our genes affect more than just how we look.

Some genes normally help control when our cells grow, divide to make new cells, or repair mistakes in DNA, or they cause cells to die when they’re supposed to. If these genes aren’t working properly, it can lead to cells growing out of control. For example:

• Changes in genes that normally help cells grow, divide, or stay alive can lead to these genes being more active than they should be, causing them to become oncogenes. These genes can result in cells growing out of control.
• Genes that normally help keep cell division under control or cause cells to die at the right time are known as tumor suppressor genes. Changes that turn off these genes can result in cells growing out of control.
• Some genes normally help repair mistakes in a cell’s DNA. Changes that turn off these DNA repair genes can result in the buildup of DNA changes within a cell, which might lead to them growing out of control.

Any of these types of DNA changes might lead to cells growing out of control and forming a tumor. To learn more, see Oncogenes, Tumor Suppressor Genes, and DNA Repair Genes.

Acquired gene mutations

Most often, the gene mutations that lead to liver cancer are acquired during a person’s lifetime, rather than being inherited from a parent. For example:

• Certain chemicals that cause liver cancer, such as aflatoxins, are known to damage the DNA in liver cells. Aflatoxins can damage the TP53 tumor suppressor gene, which normally works to prevent cells from growing too much. Damage to the TP53 gene can lead to increased growth of abnormal cells and formation of cancers.
• Hepatitis viruses can also change DNA when they infect liver cells. In some people, the virus's DNA can insert itself into a liver cell's DNA, where it may turn on the cell's oncogenes.

Some gene changes that lead to cancer might be caused by something in a person’s environment, but some might just be random events that happen inside a cell, without having an outside cause.

Liver cancer has many different causes, and many different genes are involved in its development. It is hoped that a more complete understanding of how liver cancers develop will help doctors find ways to better prevent and treat them.