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What Causes a Cancer of Unknown Primary?

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Cancers of unknown primary (CUP) include a variety of cancers, which may each have a number of different causes. This is why it’s hard to assign a particular cause to CUP.

Cancer is the result of changes in a cell’s DNA. In recent years, scientists have made great progress in learning how certain changes in DNA can cause normal cells to become cancerous. DNA is the chemical in each of our cells that makes up our genes, which control how our cells function. We usually look like our parents because they are the source of our DNA. But DNA affects more than how we look.

Some genes control when our cells grow and divide into new cells:

  • Certain genes that help cells grow and divide are called oncogenes.
  • Genes that help keep cell division under control or cause cells to die at the right time are called tumor suppressor genes.

Cancers can be caused by DNA changes that turn on oncogenes or turn off tumor suppressor genes.

Most of the DNA changes related to CUP probably occur during a person’s lifetime rather than having been inherited before birth. These are called acquired or sporadic mutations. These kinds of mutations may sometimes result from known exposures such as tobacco smoke, ultraviolet light, radiation, or certain cancer-causing chemicals, but often they occur for no apparent reason.

As scientists learn more about how cancers develop, they are also beginning to understand why some cancers tend to grow and spread so quickly that they are diagnosed as cancers of unknown primary.

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 journalists, editors, and translators with extensive experience in medical writing.

Greco FA, Hainsworth JD. Carcinoma of Unknown Primary In: DeVita VT, Lawrence TS, Rosenberg SA, eds. DeVita, Hellman, and Rosenberg’s Cancer: Principles and Practice of Oncology. 10th ed. Philadelphia, PA: Lippincott Williams & Wilkins 2015: 1719-1736.

Varadhachary GR, Lenzi R, Raber MN, Abbruzzese JL. Carcinoma of Unknown Primary In: Neiderhuber JE, Armitage JO, Doroshow JH, Kastan MB, Tepper JE, eds. Abeloff’s Clinical Oncology. 5th ed. Philadelphia, PA. Elsevier: 2014:1792-1803.

Last Revised: March 9, 2018

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