Increased Risk of Carcinoma of Unknown Primary and Other Cancers in Relatives of Patients With This Type of Cancer

Key Points

  • First-degree relatives of patients with carcinoma of unknown primary were reported to be at increased risk of carcinoma of unknown primary, lung cancer, pancreatic cancer, myeloma, and non-Hodgkin lymphoma vs relatives of carcinoma of unknown primary–free controls.
  • Second-degree relatives of patients with carcinoma of unknown primary had an elevated risk for lung cancer, pancreatic cancer, breast cancer, melanoma, and ovarian cancer vs second-degree relatives of carcinoma of unknown primary–free or cancer-free controls.

In a study from the Utah Cancer Registry reported in JAMA Oncology, Samadder et al found an increased risk of carcinoma of unknown primary and other cancers in relatives of patients with this type of cancer.

Study Details

The study was a nested case-control study including 4,160 patients with a diagnosis of carcinoma of unknown primary between 1980 and 2010 identified from the Utah Cancer Registry. Population controls without carcinoma of unknown primary were matched for sex and age 10:1 to patients with carcinoma of unknown primary, and data from relatives of patients with carcinoma of unknown primary were obtained from the Utah Population Database.

First-Degree Relatives

First-degree relatives of patients with carcinoma of unknown primary were at increased risk of this type of cancer (hazard ratio [HR] = 1.35, 95% confidence interval [CI] = 1.07–1.70), lung cancer (HR = 1.37, 95% CI = 1.22–1.54), pancreatic cancer (HR = 1.28, 95% CI = 1.06–1.54), myeloma (HR = 1.28, 95% CI = 1.01–1.62), and non-Hodgkin lymphoma (HR = 1.16, 95% CI > 1.00–1.35) compared with first-degree relatives of carcinoma of unknown primary–free controls. Significantly increased hazard ratios in analyses including only relatives of cancer-free controls were also found for carcinoma of unknown primary (1.32), lung cancer (1.43), pancreatic cancer (1.26), myeloma (1.36), and non-Hodgkin lymphoma (1.18), as well as for colon cancer (1.19) and bladder cancer (1.18).

Second-Degree Relatives

Second-degree relatives of patients with carcinoma of unknown primary had an increased risk for lung cancer (HR = 1.14, 95% CI = 1.03–1.26, vs those of carcinoma of unknown primary–free controls), pancreatic cancer (HR = 1.17, 95% CI = 1.01–1.37, vs those of cancer-free controls), breast cancer (HR = 1.09, 95% CI = 1.02–1.16, vs those of cancer-free controls), melanoma (HR = 1.09, 95% CI > 1.00–1.19, vs those of cancer-free controls), and ovarian cancer (HR = 1.20, 95% CI = 1.03–1.41, vs those of carcinoma of unknown primary–free controls; HR = 1.19, 95% CI = 1.02–1.39, vs those of cancer-free controls).

The investigators concluded: “Relatives of patients with carcinoma of unknown primary are at increased risk of carcinoma of unknown primary and several other malignant neoplasms, including lung, pancreatic, and colon cancer. The present data may suggest sites of origin for carcinoma of unknown primary and provide cancer risk information for relatives of patients with carcinoma of unknown primary that can lead to effective intervention. Relatives of patients with carcinoma of unknown primary should be aware of the elevated risks for lung, pancreatic, and colon cancer and encouraged to modify risk factors and adhere to site-specific population cancer screening.”

The study was supported by the National Cancer Institute, American Society for Gastrointestinal Endoscopy, American College of Gastroenterology, and Huntsman Cancer Institute.

N. Jewel Samadder, MD, of the Huntsman Cancer Institute, Salt Lake City, Utah, is the corresponding author of the JAMA Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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