Body mass index and colorectal cancer recurrence and mortality: A nationwide cohort study in Denmark

Obesity may exacerbate colorectal cancer (CRC) prognosis, yet previous studies have shown inconsistent findings due to methodological limitations. In this nationwide cohort study, we investigated the association between body mass index (BMI) on CRC recurrence and mortality, while examining the influence of demographic, clinical, and socioeconomic characteristics. From the Danish Colorectal Cancer Group database and population-based registries, we assembled a cohort of stage I-III CRC patients who underwent curative intent surgery between 2002 and 2020. We identified 5-year CRC recurrence and mortality using validated algorithms and registries. We estimated cumulative incidence functions (CIFs) and applied Cox regression modeling BMI via splines and categorically. We examined synergistic effects via stratification and interaction analyses. Median follow-up was 4.4 years for recurrence and 4.5 years for mortality; 5877 patients experienced CRC recurrence (CIF = 18.4%) and 6568 died (CIF = 21.8%). BMI was not associated with the recurrence of colon or rectal cancer. Underweight (BMI <18.5 kg/m²) and class II-III obesity (BMI >35 kg/m²) were associated with increased mortality, especially for rectal cancer. For rectal cancer, class II-III obesity was associated with excess mortality, particularly in younger patients (30-50 years) and males. For colon and rectal cancer, male sex, young age and comorbidities interacted to increase mortality in patients with underweight, whereas short education and smoking did so for colon cancer, and alcohol consumption for rectal cancer. Type 2 diabetes had minor influence on the associations. BMI-related mortality in CRC may be modified by demographic, clinical and socioeconomic characteristics. Targeted interventions considering the high-risk subgroups may help improve CRC outcomes.