Association between cholecystectomy and colorectal cancer: results from the National Health and Nutrition Examination Survey (NHANES) 2017-2023 and Mendelian randomization analyses.

Background: Cholecystectomy is widely used to treat gallbladder disease, but its link to colorectal cancer (CRC) remains controversial. This study aimed to assess the association between cholecystectomy and CRC by combining cross-sectional analysis with Mendelian randomization (MR). Methods: We analyzed 12,490 adults from the National Health and Nutrition Examination Survey (NHANES) 2017-2023 for the association between cholecystectomy and CRC. Weighted logistic regression models with progressive adjustments were applied: Model 1 was unadjusted, Model 2 accounted for sociodemographic factors, while Model 3 was further controlled for lifestyle, diet, and comorbidities. Subgroup and sensitivity analyses were conducted to evaluate the results' robustness. MR analysis further complemented the observational analysis and evaluated potential causality. Results: In the NHANES sample, cholecystectomy was not significantly associated with CRC after full adjustment [Model 3: odds ratio (OR) =2.06; 95% confidence interval (CI): 0.93-4.55; P=0.07], although crude and partially adjusted models showed positive associations (Model 1: OR =3.77, 95% CI: 2.08-6.83, P<0.001; Model 2: OR =2.35, 95% CI: 1.23-4.51, P=0.01). The association remained non-significant across multiple sensitivity analyses and was consistent across population subgroups. MR analysis further indicated no causal link between cholecystectomy and CRC risk. Conclusions: No statistically significant overall association was observed between cholecystectomy and CRC in our analysis.