Prior cholecystectomy may identify a biologically aggressive subset of RAS-mutated proximal colon cancer: A 13-year retrospective cohort study.

PURPOSES: Cholecystectomy (CCY) may influence the colorectal cancer (CRC) outcomes in a location-specific manner. We investigated the association between CCY history and RAS mutations in CRC, focusing on tumor location. METHODS: We retrospectively analyzed 1,340 patients with CRC diagnosed between 2012 and 2024, with an available RAS mutation status. Patients were classified into proximal and distal groups for analysis. The survival outcomes were compared using multivariate Cox proportional hazard regression models. RESULTS: CCY was associated with a higher RAS mutation prevalence in proximal CRC (58% vs. 48%) but a lower prevalence in distal CRC (30% vs. 44%). The coexistence of a history of CCY and RAS mutations was associated with worse OS in proximal CRC (p = 0.025), but not in distal CRC (p = 0.212). Among patients with proximal CRC, a multivariate analysis revealed that TNM stage III/IV (p < 0.001), non-resection initial strategy (p < 0.001), and coexistence of history of CCY and RAS mutation (p = 0.008) were independent predictors of poor OS. CONCLUSIONS: CCY had opposite effects on RAS mutation prevalence according to tumor location and, in combination with RAS mutation, identified a high-risk subgroup in proximal CRC. These findings suggest a location-specific phenomenon linking environmental changes to tumor biology. (192 words).