Prediagnostic dietary phytosterol intake, inflammatory biomarkers, and colorectal cancer survival: a cohort study

Background This study aimed to investigate the association of prediagnostic phytosterol intake (total phytosterols, β-sitosterol, campesterol, stigmasterol, β-sitostanol, and campestanol) with colorectal cancer (CRC)-specific and overall survival, and to explore the potential mediating role of systemic inflammation. Methods This study included 2,799 incident CRC patients enrolled in the Guangdong Colorectal Cancer Cohort between 2010 and 2021, who were prospectively followed until December 1, 2024. Usual dietary intake during the year before diagnosis was assessed using a validated food frequency questionnaire. Inflammatory markers were measured from fasting blood samples collected at enrollment, and the pan-immune-inflammation value (PIV) was calculated as neutrophil count × platelet count × monocyte count ÷ lymphocyte count. Multivariable Cox proportional hazards models and mediation analysis were conducted to assess associations between phytosterol intake, inflammation, and CRC survival, adjusting for demographic, clinical, and dietary confounders. Results During a median follow-up of 78.60 months, 717 deaths were recorded, of which 636 were attributable to CRC. Higher intakes of total phytosterols, β-sitosterol, and stigmasterol were significantly associated with improved CRC-specific survival (HRs for Q4 vs. Q1: 0.76 [95% CI: 0.60, 0.95], 0.71 [0.56, 0.90], and 0.75 [0.60, 0.95], respectively). Similar associations were observed for overall survival. The PIV showed a significant but modest mediating effect on the associations of β-sitosterol intake with CRC-specific and overall survival (indirect effect HRs = 0.99 [95% CI: 0.96, 1.00] for both; P = .016 and 0.018, respectively). Conclusions Higher prediagnostic dietary phytosterol intake was associated with improved CRC survival partially through inflammation-related pathways.