Meat consumption and Cancer of Unknown Primary (CUP) risk: results from the Netherlands Cohort Study on diet and cancer

Purpose: Cancer of Unknown Primary (CUP) is a metastasized cancer for which the primary tumor origin remains unidentifiable during a patient's lifetime. CUP prognosis is highly unfavorable with a median survival of 1.7 months. Research into CUP etiology with respect to dietary factors is particularly scarce. This study investigates whether meat consumption is associated with CUP risk, and whether there is multiplicative interaction between sex or cigarette smoking status and the relationship of meat consumption and CUP risk. Methods: Data was utilized from the prospective Netherlands Cohort Study (NLCS) that includes 120,852 participants aged 55-69 years from 204 Dutch municipalities. All participants completed a self-administered questionnaire on diet and other cancer risk factors at baseline. Habitual meat consumption was measured with respect to red meat (overall), beef, pork, minced meat, liver, processed meat, poultry and fish. The food-frequency questionnaire had been validated against a 9-day diet record and was tested for reproducibility. Cancer follow-up was established through record linkage to the Netherlands Cancer Registry and the Dutch Pathology Registry. As a result, a total of 899 CUP cases and 4,111 subcohort members with complete and consistent dietary data were available for case-cohort analyses after 20.3 years of follow-up. Multivariable adjusted hazard ratios (HRs) were calculated using proportional hazards models, and were adjusted for age, sex, alcohol consumption, cigarette smoking variables (status, frequency, duration), and total energy intake. Results: In general, we observed no association between red meat (overall) consumption and CUP risk (multivariable adjusted HR for Q4 vs. Q1: 1.04, 95% CI: 0.83-1.30, Ptrend = 0.31). An increased risk was observed between beef consumption and CUP, for which a statistically significant trend was found (HR for Q4 vs. Q1: 1.22, 95% CI: 0.99-1.52, Ptrend = 0.02). The effect of beef consumption on CUP risk appeared to be stronger in women (HR Q4 vs. Q1: 1.47, 95% CI: 1.04-2.07, Ptrend = 0.004). A statistically significant association was also observed between processed meat consumption and CUP risk (HR for Q4 vs. Q1: 1.40, 95% CI: 1.12-1.75, Ptrend = 0.006). Our sex-stratified analysis indicated that the effect of processed meat consumption on CUP risk was more pronounced in women (HR for Q4 vs. Q1: 1.53, 95% CI: 1.08-2.16, Ptrend = 0.001), than in men (HR Q4 vs. Q1: 1.33, 95% CI: 0.99-1.79, Ptrend = 0.15). In contrast, no associations were observed between poultry or fish consumption and CUP risk (HR for C4 vs. C1: 0.97, 95% CI: 0.79-1.21, Ptrend = 0.28 & HR for Q4 vs. Q1: 1.25, 95% CI: 0.99-1.57, Ptrend = 0.29, respectively). We found no multiplicative interaction between cigarette smoking status and meat consumption and CUP risk. Conclusion: Beef and processed meat consumption appear to be associated with increased CUP risk in women. In men, there appeared to be a non-significant positive association between processed meat consumption and CUP risk.

Citation Format: Karlijn Hermans, Piet Van den Brandt, Caroline Loef, Rob Jansen, Leo Schouten. Meat consumption and Cancer of Unknown Primary (CUP) risk: results from the Netherlands Cohort Study on diet and cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB088.