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

Abstract

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.

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

“…Age, sex, smoking and alcohol consumption were considered as predefined confounders and were used in all statistical models, as these factors have been demonstrated to be associated with CUP (K. Hemminki, Chen, et al, 2015;Hermans et al, 2021;Kaaks et al, 2014;Vajdic et al, 2019). Potential confounders (BMI, socio-economic status, physical activity and diabetes status) were evaluated using the backward elimination procedure.…”

“…Additionally, modifiable lifestyle-related risk factors have been highlighted as influential. For instance, CUP is associated with cigarette smoking (K. Hemminki, Chen, et al, 2015;Hermans et al, 2021;Kaaks et al, 2014;Vajdic et al, 2019). Similarly, alcohol consumption is also associated with CUP risk in a dose-response relationship (Hermans et al, 2021).…”

“…For instance, CUP is associated with cigarette smoking (K. Hemminki, Chen, et al, 2015;Hermans et al, 2021;Kaaks et al, 2014;Vajdic et al, 2019). Similarly, alcohol consumption is also associated with CUP risk in a dose-response relationship (Hermans et al, 2021). A weaker association was found for waist circumference which was no longer statistically significant after adjusting for confounders (Kaaks et al, 2014).…”

Meat consumption and cancer of unknown primary (CUP) risk: results from The Netherlands cohort study on diet and cancer

“…By assessing lifestyle factors that are potentially 1 3 associated with the disease, however, it may be possible to prevent future CUP patients. Certain modifiable risk factors, such as cigarette smoking and alcohol consumption, have been linked to the development of CUP [9][10][11][12]. Nonetheless, the relationship between diet and CUP has been less well studied, and that is particularly true with respect to meat consumption [11].…”

The Treatment for a Patient with Cancer of Unknown Primary: A Case Report

“… 1 Alcohol consumption and cigarette smoking have a correlation with increasing CUP risk. 2 CUP accounts for approximately 2–5% of all new tumors. 3 In a previous study, CUP was diagnosed as a malignant tumor and metastasis was confirmed through histology.…”