Longitudinal relations between lifestyle factors and systemic inflammation in colorectal cancer: Results from the PROFILES registry

Introduction
Lifestyle factors are involved in carcinogenesis and disease progression in colorectal cancer (CRC) and contribute to systemic inflammation. We examined individual and group-level trajectories of associations between lifestyle factors (smoking, alcohol use, body mass index (BMI), and physical activity) and systemic inflammation from diagnosis until 24 months thereafter.

Methods
We used data from the PROCORE-study, a prospective cohort of stage I–IV CRC patients (n = 411). Patients completed lifestyle questionnaires and provided blood samples at diagnosis (pre-treatment), and 12 and 24 months thereafter. Linear mixed models examined associations between lifestyle and inflammation (C-Reactive Protein (CRP), interleukin-(IL)1α, IL-1β, IL-6, IL-8, IL-10, IL-17A, IL-22, Interferon-gamma (IFN-γ), soluble Tumor Necrosis Factor Receptors (sTNFR)I/II), while adjusting for demographics, cancer stage, comorbidities, and time since diagnosis.

Results
Biomarkers remained largely stable, though IL-22 declined, whereas TNFRII increased over time. IL-8, IL-1β, and IL-10, levels decreased at 12 and increased at 24 months follow-up. Smoking was associated with higher CRP (p = .003). Obese patients showed elevated IFN-γ (p = .001) and sTNFRI (p < .001), while overweight patients had increased sTNFRI (p = .014) and IL-1α (p = .040), and reduced IL-1β (p = .039). Underweight patients displayed higher IL-22 (p = .038). Physical activity was associated with lower IFN-γ (p = .020) and sTNFRII (p = .044). Alcohol consumption was linked to lower IL-1β and IL-10, while occasional and moderate use were related to lower IL-17A and IFN-γ.

Conclusion
Smoking, obesity, and alcohol use were linked to higher inflammation, whereas physical activity showed protective effects in CRC patients. Findings highlight the importance of integrating lifestyle support into survivorship care.