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Background: Little is known about the risk factors for cancer of unknown primary site (CUP). We examined the demographic, social and lifestyle risk factors for CUP in a prospective cohort of 266,724 people aged 45 years and over in New South Wales, Australia. Methods: Baseline questionnaire data were linked to cancer registration, hospitalisation, emergency department admission, and mortality data. We compared individuals with incident cancer registry-notified CUP (n = 327) to two sets of controls randomly selected (3:1) using incidence density sampling with replacement: (i) incident cancer registry-notified metastatic cancer of known primary site (n = 977) and (ii) general cohort population (n = 981). We used conditional logistic regression to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Results: In a fully adjusted model incorporating self-rated overall health and comorbidity, people diagnosed with CUP were more likely to be older (OR 1.05, 95% CI 1.04–1.07 per year) and more likely to have low educational attainment (OR 1.77, 95% CI 1.24–2.53) than those diagnosed with metastatic cancer of known primary. Similarly, compared to general cohort population controls, people diagnosed with CUP were older (OR 1.10, 95% CI 1.08–1.12 per year), of low educational attainment (OR 1.69, 95% CI 1.08–2.64), and current (OR 3.42, 95% CI 1.81–6.47) or former (OR 1.95, 95% CI 1.33–2.86) smokers. Conclusion: The consistent association with educational attainment suggests low health literacy may play a role in CUP diagnosis. These findings highlight the need to develop strategies to achieve earlier identification of diagnostically challenging malignancies in people with low health literacy.

Original publication




Journal article


Cancer Epidemiology

Publication Date





156 - 161