Extensive study on the associations of 12 composite inflammatory indices with colorectal cancer risk and mortality: a cross-sectional analysis of NHANES 2001–2020

BACKGROUND: Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide, with inflammation emerging as a critical factor in its development. We conducted the most comprehensive analysis to date of various inflammatory indices, investigating the associations between these indices and both the risk and mortality of CRC, utilizing nationwide data from the National Health and Nutrition Examination Survey (NHANES). METHODS: Data were sourced from NHANES cycles spanning 2001 to 2020. After applying strict inclusion and exclusion criteria, 18 470 eligible samples were analyzed. Twelve composite inflammatory indices were calculated based on peripheral blood cell counts. After adjusting for confounders, we employed logistic regression models to investigate the association between inflammatory indices and CRC risk, supplemented by forest plots, generalized additive model (GAM), and receiver operating characteristic (ROC) curves for a comprehensive understanding. To assess the association between these indices and CRC mortality, we utilized Cox proportional hazards regression analysis, augmented by restricted cubic splines for flexibility, survival curves for visual representation, and ROC curves for discriminative ability. RESULTS: Elevated neutrophil-to-lymphocyte ratio (NLR) and reduced lymphocyte-to-monocyte ratio (LMR) were significantly associated with increased CRC risk (NLR: Q4 vs. Q1: OR = 2.137, 95% CI = 1.212-3.765, P -trend = 0.045; LMR: Q4 vs. Q1: OR = 0.503, 95% CI = 0.274-0.923, P -trend = 0.027). In terms of mortality risk, low LMR, high neutrophil-to-platelet ratio (NPR), and high systemic immune-inflammation index (SII) showed associations with adverse outcomes. Higher SII ( P = 0.0459), NPR ( P = 0.0333) levels trended toward poorer prognosis, while higher LMR levels predicted better prognosis ( P = 0.0056). The association between these indicators and the risk and prognosis of CRC tends to be more of a nonlinear correlation. In terms of their performance in assessing the risk and prognosis of CRC, there is no significant difference between single indicators and combined indicators. CONCLUSIONS: Elevated NLR and reduced LMR may serve as non-invasive biomarkers for early detection and risk stratification of CRC. Low LMR, high NPR, and high SII are linked to adverse mortality outcomes. Dynamic monitoring based on these indices has the potential to offer new insights and directions for the diagnosis and treatment of CRC.