Introduction
Little is known about the risk factors for cancer of unknown primary site (CUP), a high-burden malignancy.
Aims
We examined the association between demographic, social and lifestyle factors, comorbid disease, health service use, and risk of cancer registry-notified CUP in a prospective cohort of 266,724 people aged 45 years and over in NSW, Australia.
Methods
45 and Up Study baseline questionnaire data were linked by the CHeReL to the NSW Cancer Registry, the NSW Registry of Births, Deaths and Marriages, and health service records (NSW Admitted Patients Data Collection, NSW Emergency Department Data Collection, and Medicare Benefits Schedule, the latter supplied by the Department of Human Services) 4-27 months prior to diagnosis. Using a nested case-control design, we compared individuals with incident cancer registry-notified CUP (n=327) to controls randomly selected (3:1) from the general cohort population (n=981). We used conditional logistic regression to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs).
Results
In the fully adjusted model, risk of CUP increased with increasing age (OR 1.10, 95%CI 1.08-1.12 per year), current (OR 3.42, 95%CI 1.81-6.47) and former (OR 1.95, 95%CI 1.33-2.86) smoking, low educational attainment (OR 1.69, 95%CI 1.08-2.64), poor compared to excellent self-rated overall health (OR 6.22, 95%CI 1.35-28.6), and a personal history of diabetes (OR 1.89, 95%CI 1.15-3.10) or cancer (OR 1.62, 95%CI 1.03-2.57). Risk of CUP decreased in those with a personal history of anxiety (OR 0.28, 95%CI 0.12-0.63). Neither tertiary nor community-based health service use independently predicted CUP.
Conclusions
Risk of CUP appears increased in people who are older, more unwell and less well-educated. Several novel associations are worthy of further investigation to elucidate modifiable risk factors. Of interest is the implied association with low health literacy, and with low self-rated overall health, which warrant exploration to identify opportunities for earlier cancer diagnosis.