ASPO Abstracts
Colorectal cancer molecular subtypes and mortality
Category: Molecular Epidemiology & Environment
Conference Year: 2023
Abstract Body:
Purpose Colorectal cancer (CRC) molecular subtypes, identified based on tumor marker combinations, may play a role in survival. These subtypes reflect different etiologic pathways and relate to differences in the distribution of tumor site, sex, age, and stage of diagnosis. Growing evidence also supports the distinct survival profiles of CRC molecular subtypes. Methods Participants from two population-based studies were diagnosed with invasive CRC between 1998 and 2018 and followed for survival. Tumor samples were collected from 2,256 participants and classified into 5 subtypes based on microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and somatic mutations in BRAF and KRAS, as follows: 1) Type 1 (MSI-high, CIMP-high, BRAF-mutated, KRAS-wildtype), 2) Type 2 (microsatellite stable (MSS)/MSI-low, CIMP-high, BRAF-mutated, KRAS-wildtype), 3) Type 3 (MSS/MSI-low, non-CIMP/CIMP-low, BRAF-wildtype, KRAS- mutated), 4) Type 4 (MSS/MSI-low, non-CIMP/CIMP-low, BRAF-wildtype, KRAS-wildtype), and 5) Type 5 (MSI-high, non-CIMP/CIMP-low, BRAF-wildtype, KRAS-wildtype). Multiple imputation was used to impute tumor markers for those missing data on 1-3 markers used in subtype classification. Cox regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CIs) to assess associations between subtypes and CRC-specific mortality, adjusting for sex, smoking history, tumor site, and study. Results Compared to participants with the predominant Type 4 subtype (50%), participants with Type 2 tumors (2%) had the poorest survival (HR=1.63, 95% CI: 1.47, 1.81). Participants with Type 3 tumors also had significantly poorer survival (HR=1.19, 95% CI: 1.14, 1.24). In contrast, participants with Type 5 tumors experienced the most favorable survival (HR=0.39, 95% CI: 0.34, 0.44). Observed associations persisted after adjustment for stage. Associations were consistent across strata defined by sex and stage, although associations for Type 2 were most pronounced among males and those with distant stage CRC. Conclusions We observed significant associations between CRC molecular subtype and CRC survival, with consistent patterns of association across sex and stage. These findings support the clinical significance of these subtype classifications
Keywords: molecular subtypes, colorectal cancer, mortality