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Cancer of Unknown Primary Risk Factors

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A risk factor is anything that affects a person’s chance of getting a disease such as cancer. Different cancers have different risk factors. Some risk factors, like smoking, can be changed. Others, like a person's age or family history, can't be changed.

But having a risk factor, or even several, does not mean that a person will get the disease, and many people get cancer without having any known risk factors.

Since the exact type of cancer is not known, it’s hard to identify factors that might affect risk for cancer of unknown primary (CUP). These cancers are also a very diverse group, making this issue even more complicated. But there is research that provides some information about CUP risk factors.

Smoking is probably an important risk factor for CUP. More than half of patients with CUP have a history of smoking. When autopsy studies are done, many cancers of unknown primary are found to have started in the pancreas, lungs, kidneys, throat, larynx, or esophagus. Smoking increases the risk for all of these cancers.

Some other cancers of unknown primary are eventually found to have started in the stomach, colon, rectum, or ovaries. Diet, nutrition, and weight are factors that have been linked to these cancers. For more information, see the specific type of cancer.

Melanoma (an aggressive type of skin cancer) is another source of cancer of unknown primary. An important melanoma risk factor is exposure to ultraviolet radiation in sunlight.

Overall, however, there are no factors that specifically increase the risk of cancer of unknown primary. Even in people who may have one or more of the risk factors above, it’s not possible to know for sure if these factors contributed to the cancer.

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.

Hemminki K, Chen B, Melander O, Manjer J, Hallmans G, Hemminki A. Smoking and body mass index as risk factors for subtypes of cancer of unknown primary. Int J Cancer. 2015 Jan 1;136(1):246-7. doi: 10.1002/ijc.28969.

Löffler H, Puthenparambil J, Hielscher T, Neben K, Krämer A. Patients with cancer of unknown primary: A retrospective analysis of 223 patients with adenocarcinoma or undifferentiated carcinoma. Dtsch Arztebl Int. 2014 Jul 7;111(27-28):481-7. doi: 10.3238/arztebl.2014.0481.

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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