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What Causes Liver Cancer?

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Although several risk factors for liver cancer are known (see Liver Cancer Risk Factors), exactly how these may lead normal liver cells to become cancerous is only partially 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 DNA affects more than just how we look.

Some genes control when cells grow, divide into new cells, and die.

  • Genes that help cells to grow and divide and stay alive are called oncogenes.
  • Genes that keep cell division under control, repair mistakes in DNA, or cause cells to die at the right time are called tumor suppressor genes.

Cancers can be caused by DNA changes (mutations) that turn on oncogenes or turn off tumor suppressor genes. Several different genes usually need to have changes for a cell to become cancerous.

Certain chemicals that cause liver cancer, such as aflatoxins, are known to damage the DNA in liver cells. For example, studies have shown that 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 patients, the virus's DNA can insert itself into a liver cell's DNA, where it may turn on the cell's oncogenes.

Liver cancer clearly has many different causes, and there are undoubtedly many different genes 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.

The American Cancer Society medical and editorial content team

Our team is made up of doctors and oncology certified nurses with deep knowledge of cancer care as well as editors and translators with extensive experience in medical writing.

Abou-Alfa GK, Jarnigan W, Dika IE, D’Angelica M, Lowery M, Brown K, et al. Ch. 77 - Liver and Bile Duct Cancer. In: Niederhuber JE, Armitage JO, Doroshow JH, Kastan MB, Tepper JE, eds. Abeloff’s Clinical Oncology. 6th ed. Philadelphia, Pa: Elsevier; 2020:1314–1341.

Buck CB, Ratner L, and Tosato G. Ch. 7 – Oncogenic Viruses. In: DeVita VT, Lawrence TS, Rosenberg SA, eds. DeVita, Hellman, and Rosenberg's Cancer: Principles and Practice of Oncology. 11th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2019:98-113.

Schwartz JM and Carithers RL. Epidemiology and etiologic associations of hepatocellular carcinoma. UpToDate website. https://www.uptodate.com/contents/epidemiology-and-etiologic-associations-of-hepatocellular-carcinoma. Updated December 12, 2019. Accessed March 12, 2019.

Last Revised: April 1, 2019

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