Adherence to the World Cancer Research Fund and the American Institute for Cancer Research lifestyle recommendations for cancer prevention and Cancer of Unknown Primary risk

Background & aims: The World Cancer Research Fund (WCRF) and American Institute for Cancer Research (AICR) updated their cancer prevention recommendations in 2018. Adherence to these recommendations has been associated with lower cancer risk and mortality. However, adherence in relation to Cancer of Unknown Primary (CUP) risk has not been studied. This study investigates whether adherence to the WCRF/AICR recommendations is associated with CUP risk. Methods: Data from the prospective Netherlands Cohort Study on diet and cancer was used to measure adherence to the recommendations in relation to CUP risk. The cohort includes 120 852 participants (aged 55–69 years), who completed a self-administered questionnaire on cancer risk factors at baseline. Adherence was investigated with respect to body fatness, physical activity, plant foods, meat consumption and alcohol. Incident CUP cases were identified through record linkage to the Netherlands Cancer Registry and Dutch Pathology Registry. A follow-up of 20.3 years, resulted in 856 incident CUP cases and 3911 subcohort members with complete information available for case-cohort analyses. Multivariable adjusted hazard ratios were estimated using proportional hazards models and were adjusted for age at baseline, sex, cigarette smoking (status, frequency, and duration) and total energy intake. Results: Highest adherence appeared to be associated with decreased CUP risk in the age-sex adjusted model (HR: 0.76, 95% CI: 0.62–0.92). After additional adjustment for cigarette smoking (status, frequency, and duration), the association attenuated and was no longer statistically significant. No multiplicative interactions were observed between sex nor smoking status and overall adherence in relation to CUP. Conclusion: Within this cohort, highest adherence to the WCRF/AICR recommendations is not statistically significantly associated with decreased CUP risk after multivariable adjustment.