Associations between degree of food processing, inflammatory biomarkers and colorectal cancer survival: a prospective...

The association between NOVA-classified food processing level and colorectal cancer (CRC) prognosis remains unclear, particularly regarding the potential mediating role of inflammation. We included 2799 patients from Guangdong Colorectal Cancer Cohort. Dietary intake was assessed using a validated food frequency questionnaire, with intakes quantified in g day^-1 and classified according to the NOVA system. Six inflammatory biomarkers (C-reactive protein and five hematological indices) were evaluated. Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for overall survival (OS), CRC-specific survival (CSS), and recurrence- or metastasis-free survival (RMFS). Isocaloric substitution models tested replacing 25 g of ultra-processed foods (UPF) or processed foods (NOVA 3) with unprocessed/minimally processed foods (NOVA 1). Mediation analyses quantified the contribution of inflammation and stratified analyses examined effect modification by sex, age and cancer site. Over a median follow-up of 77.63 months, 715 deaths (647 CRC-specific) and 557 instances of recurrence/metastasis occurred. Higher NOVA 1 consumption was associated with improved OS (HR_{Q4 vs. Q1}: 0.73, 95% CI: 0.56, 0.96) and CSS (HR_{Q4 vs. Q1}, 0.72, 95% CI: 0.54, 0.96), particularly in rectal cancer patients (P-interaction < 0.05). Replacing UPFs with NOVA 1 improved OS (HR: 0.992, 95% CI 0.984, 0.999) and CSS (HR: 0.990, 95% CI 0.982, 0.998), with similar associations for NOVA 3. Inflammation mediated 5.58-9.40% of these associations. Collectively, higher NOVA 1 consumption was associated with improved OS and CSS among CRC patients, partly through reduced systemic inflammation. Substituting UPFs or NOVA 3 with NOVA 1 may confer additional survival benefits.