Targeted plasma lipidomic profiles associated with colorectal cancer risk and effect modifications by common risk factors and particulate matter exposure.

The role of specific lipids in colorectal cancer (CRC) incidence remains unclear. We aimed to evaluate associations of plasma lipids with CRC risk and the modification effects of common risk factors and ambient particulate matter (PM) exposure. We conducted a nested case-control study within the Dongfeng-Tongji cohort, including 218 cases and 436 matched controls. Plasma levels of 155 lipids were determined by UPLC-MS/MS. The conditional logistic regression and LASSO regression identified nine lipids as potential CRC risk biomarkers. Specifically, triacylglycerol (TAG) 56:7 [20:4], cholesterol ester (CE) 20:2 (1), CE 22:5, lysophosphatidylethanolamine (LPE) 18:2, and sphingomyelin (SM) 32:2 were associated with decreased CRC risk (adjusted ORs per SD: 0.05-0.68), while LPE 18:0, diglycerol (DAG) 16:1/17:1, SM 38:1, and SM 34:0 were associated with increased CRC risk (ORs per SD: 1.60-6.19). Compared to the traditional factors, these lipids exerted improvement of 35.4% in area under the curve (AUC) discriminations for CRC (AUC = 0.972 vs. 0.618). Notably, the associations between specific lipids and CRC risk were modified by BMI (TAG 56:7 [20:4]), smoking (LPE 18:0, DAG 16:1/17:1), alcohol consumption (SM 32:2), healthy diet (TAG 56:7 [20:4]), and PM exposure (TAG 56:7 [20:4], DAG 16:1/17:1, SM 38:1, LPE 18:2) (all P_interaction <0.05). Our study identified 9 plasma lipids with significant associations with CRC risk and underscored the effect modifications of common risk factors and PM exposure on these associations. These findings provide new insights into the links between specific lipids and CRC development.