Uncovering the aetiology of cancers of unknown primary site

Risk for Cancer of Unknown Primary Site, uncovering the aetiology of a neglected disease – research study

  • Topic: Combination of cancers
  • Institution: Maastricht University
  • Country: Netherlands
  • Status: Completed
Researcher: Leo Schouten


  • Prof Piet Van den Brandt, GROW-School for Oncology and Dev Biology, Maastricht University, Netherlands
  • Dr Caroline Schroten-Loef, Comprehensive Cancer Organization the Netherlands, Netherlands
  • Dr Rob LH Jansen, Maastricht University Medical Centre, Dept Internal Medicine, Netherlands


Cancer of Unknown Primary (CUP) is a metastatic cancer with no identifiable primary tumour origin. Sometimes metastases are the first symptom while the primary tumour cannot be found despite the completion of initial diagnostic workup and histological and/or cytological verification.


Investigate the association between individual lifestyle components: 1) alcohol consumption, cigarette smoking, anthropometry, physical activity, vegetable and fruit consumption, and meat consumption in relation to CUP risk, and lifestyle as an overall component by studying 2) whether adherence to the WCRF/AICR lifestyle recommendations for cancer prevention is associated with CUP risk. Combine our findings with the existing epidemiological evidence in an up-to-date comprehensive review.

How it was done

Data from the Netherlands Cohort Study on diet and cancer, a prospective cohort including 120,852 participants (58,279 men and 62,573 women) aged 55-69 years at baseline in 1986 was used. All participants completed a mailed, self-administered questionnaire on dietary habits and other cancer risk factors at baseline in 1986. Incident CUP cases were identified through record linkage of the cohort with the Netherlands Cancer Registry (NCR) and the Dutch Pathology Registry (PALGA). Participants were followed up for 20.3 years (until 31 December 2006).


Alcohol consumption and cigarette smoking appeared to be associated with an increased CUP risk. For alcohol consumption, participants with the highest alcohol intake levels had a higher CUP risk. Cigarette smoking status, smoking frequency, smoking duration, and time since smoking cessation were all associated with increased CUP risk. Beef and processed meat consumption were associated with increased CUP risk. The sex-stratified analysis indicated that the association with beef and processed meat consumption and CUP risk became stronger in women. Participants with the highest adherence to the recommendations had a decreased CUP risk in the age- and sex-adjusted analysis. However, the association between adherence to the recommendations and CUP risk was no longer statistically significant after additional adjustments for smoking behaviour.


The prognosis for CUP patients is bleak and the great majority of patients do not survive one year after diagnosis. In general, cancer treatment(s) is targeted on the primary tumour origin, however, due to the inability of identifying the origin, it may be more beneficial to focus on disease prevention.

Grant publications