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A comprehensive multi-omics analysis was conducted on Chinese colorectal cancer (CRC) patients, identifying three distinct subtypes. Among these, the S_I subtype exhibited the worst prognosis. This s...

For the discovery phase of this study, we utilized colon adenocarcinoma (COAD) samples obtained from TCGA10. The subsequent replication phase was carried out through a meta-analysis, incorporating data from studies on colon cancer (GSE131013, GSE42752, E-MTAB-7036 and GSE199057)11,12,13,14, rectal cancer (TCGA-READ and GSE39958)15 and colorectal cancer (GSE101764, GSE77954 and E-MTAB-3027)16,17,18. Patients were classified as EOCRC (<50 years) or LOCRC (≥70 years). This resulted in a discovery dataset containing 31 EOCRC and 100 LOCRC patients, whereas the replication cohort incorporated 83 EOCRC and 272 LOCRC patients. Population characteristics are presented in Table 1, with a detailed discovery cohort characterization in Supplementary Table 1. Exposome-related DNA methylation marker sets The exposome’s association with EOCRC versus LOCRC was evaluated using 29 lifestyle and environmental factors, which we define here as the exposome, acknowledging its broader scope. The analyzed traits encompassed 11 lifestyle factors: the Alternative Healthy Eating Index (AHEI), alcohol consumption, birthweight, body mass index (BMI) (continuous variable in kg m−2), cannabis use, coffee consumption, education level, Mediterranean Diet Score (MDS), obesity (defined as ≥30 kg m−2), smoking habits and smoking inference model (smoking-Maas). Furthermore, we examined four air pollution particles: nitrogen dioxide (NO2), polychlorinated biphenyls (PCBs) and particulate matter (PM) < 2.5...