S535 Incidence of Colorectal Cancer in Patients With Cholelithiasis With Versus Without Cholecystectomy: A Large Real-World Cohort Study

Zhexiang He; Chenyu Sun; Saivishnu Doosetty; Ishtiaq Ahmad

doi:10.14309/01.ajg.0001211392.87062.b9

Introduction: Gallstones may increase colorectal cancer (CRC) risk through bile flow obstruction, altered fat metabolism, and chronic intestinal inflammation. However, the relationship between cholecystectomy and CRC risk in patients with cholelithiasis remains unclear. Therefore, we evaluated CRC incidence using a large multicenter electronic health record database. Methods: We conducted a retrospective cohort study using the TriNetX Global Collaborative Network (>170 healthcare organizations). Adult patients (≥18 years) with cholelithiasis were stratified into cholecystectomy and non-cholecystectomy cohorts, with 1:1 propensity score matching to balance baseline characteristics. The primary outcome was incident CRC (ICD-10: C18), excluding patients with prior CRC. Risk and Kaplan–Meier survival analyses were performed, including subgroup analyses by sex and age. Results: After matching, 96,968 patients with cholecystectomy were compared to 96,483 without. CRC occurred in 440 (0.5%) vs 618 (0.6%), respectively. The research result indicated that cholecystectomy was associated with a reduced CRC risk (risk ratio [RR] 0.71, 95% CI 0.63–0.80; P < 0.001) and lower hazard (hazard ratio [HR] 0.72, 95% CI 0.64–0.81; P = 0.006). Among females (70,850 matched pairs), CRC incidence was 0.4% vs 0.6%, with a stronger risk reduction (RR 0.59, 95% CI 0.50–0.68; P < 0.001; HR 0.59, 95% CI 0.51–0.69; P < 0.001). Among males (26,037 matched pairs), CRC incidence was 0.7% vs 0.9%, with a modest reduction (RR 0.80, 95% CI 0.66–0.96; P = 0.018), with borderline survival significance (HR 0.80, 95% CI 0.66–0.96; log-rank P = 0.019). Age-stratified analysis demonstrated a gradient effect. In patients aged 18–64 years (58,792 matched pairs), CRC incidence was 0.1% vs 0.3%, showing the strongest reduction (RR 0.36, 95% CI 0.27–0.47; P < 0.001; HR 0.38, 95% CI 0.29–0.50; P = 0.035). In patients ≥65 years (38,641 matched pairs), CRC incidence was 0.97% vs 1.29%, with a more modest reduction (RR 0.75, 95% CI 0.65–0.85; P < 0.001; HR 0.71, 95% CI 0.62–0.81; P = 0.03). Conclusion: In this large propensity score–matched study, cholecystectomy in patients with cholelithiasis was associated with a reduced risk of CRC, particularly among younger patients and females. The attenuated association observed in older patients and males suggests potential age- and sex-specific differences in colorectal carcinogenesis after cholecystectomy. Further prospective studies are needed to confirm these findings and clarify the underlying mechanisms.

S535 Incidence of Colorectal Cancer in Patients With Cholelithiasis With Versus Without Cholecystectomy: A Large Real-World Cohort Study

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