Family history of cancer in first degree relatives and risk of cancer of unknown primary

A.L.R. Grewcock, K.E.P.E. Hermans*, M.P. Weijenberg, P.A. van den Brandt, C. Loef, R.L.H. Jansen, L.J. Schouten

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Objective Cancer of Unknown Primary (CUP) refers to the presence of metastatic lesions, with no identifiable primary site during the patient's lifetime. Poor survival and lack of available treatment highlight the need to identify potential CUP risk factors. We investigated whether a family history of cancer is associated with increased CUP risk. Methods We performed a case cohort analysis using data from the Netherlands Cohort Study, which included a total of 963 CUP cases and 4,288 subcohort members. A Cox Proportional Hazards Regression was used to compare CUP risk in participants who reported to have a family member with cancer to those who did not, whilst adjusting for confounders. Results In general, we observed no increased CUP risk in those who reported a family history of cancer. CUP risk appeared slightly increased in those who reported cancer in a sibling (HR: 1.16, 95% CI: 0.97-1.38), especially in those with a sister with cancer compared with those without (HR: 1.23, 95% CI: 0.99-1.53), although these findings are not statistically significant. Conclusion Having a family history of cancer is not an independent risk factor of CUP.
Original languageEnglish
Article numbere13485
Number of pages9
JournalEuropean Journal of Cancer Care
Issue number6
Early online date5 Jul 2021
Publication statusPublished - Nov 2021


  • Cancer of Unknown Primary (CUP)
  • family history of cancer
  • prospective cohort study

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