Alcohol consumption, cigarette smoking and cancer of unknown primary risk: Results from the Netherlands Cohort Study

• Published in: International journal of cancer 2021-04, Vol.148 (7), p.1586-1597
• Main Authors: Hermans, Karlijn E. P. E., Brandt, Piet A., Loef, Caroline, Jansen, Rob L. H., Schouten, Leo J.
• Format: Article
• Language: English
• Subjects: Alcohol; Alcohol use; Cancer; Cancer Epidemiology; cancer of unknown primary (CUP); Cigarette smoking; Cohort analysis; Drinking behavior; Ethanol; Malignancy; Medical research; prospective cohort study; Risk factors; Smoking; Tobacco smoking; Tumors
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.33328

Cancer of unknown primary (CUP) is a metastasised malignancy with no identifiable primary tumour origin. Despite the frequent occurrence and bleak prognosis of CUP, research into its aetiology is scarce. Our study investigates alcohol consumption, tobacco smoking and CUP risk. We used data from the Netherlands Cohort Study, a cohort that includes 120 852 participants aged 55 to 69 years, who completed a self‐administered questionnaire on cancer risk factors at baseline. Cancer follow‐up was established through record linkage to the Netherlands Cancer Registry and Dutch Pathology Registry. After 20.3 years of follow‐up, 963 CUP cases and 4288 subcohort members were available for case‐cohort analyses. Multivariable‐adjusted hazard ratios (HRs) were calculated using proportional hazard models. In general, CUP risk increased with higher levels of alcohol intake (Ptrend = .02). The association was more pronounced in participants who drank ≥30 g of ethanol per day (HR: 1.57, 95% confidence interval [CI]: 1.20‐2.05) compared to abstainers. Current smokers were at an increased CUP risk (HR: 1.59, 95% CI: 1.29‐1.97) compared to never smokers. We observed that the more the cigarettes or the longer a participant smoked, the higher the CUP risk was (Ptrend = .003 and Ptrend = .02, respectively). Interaction on additive scale was found for participants with the highest exposure categories of alcohol consumption and cigarette smoking frequency and CUP risk. Our findings demonstrate that alcohol consumption and cigarette smoking are associated with increased CUP risk. Lifestyle recommendations for cancer prevention regarding not drinking alcohol and avoiding exposure to smoking are therefore also valid for CUP. What's new? Little is known about factors that raise the risk of cancer of unknown primary (CUP), in which metastases have no identifiable primary tumor origin. This prospective study examined possible associations between CUP and alcohol consumption and cigarette smoking, using sex‐stratified analyses and assessing variables such as smoking frequency and duration. Analyses show that higher alcohol consumption, current cigarette smoking, more cigarettes smoked, and longer smoking duration are associated with increased CUP risk. The data highlight the significance of lifestyle factors in CUP risk and suggest that lifestyle recommendations regarding alcohol intake and smoking are relevant to CUP prevention.