基于孟德尔随机化分析胆囊切除与结直肠肛管恶性肿瘤发生的关系

Analysis of the relationship between cholecystectomy and colorectal and anal cancers based on Mendelian randomization

目的 基于两样本孟德尔随机化(TSMR)分析胆囊切除术后与结直肠肛管恶性肿瘤发生之间的关系。方法 胆囊切除术后与结直肠肛管恶性肿瘤相关的单核甘酸多态性(SNP)数据分别来自公开发表的生物数据库,并对基于全基因组关联研究(GWAS)数据库的所有汇总数据进行数据分析,选择与胆囊切除密切关联的遗传位点作为工具变量,分别以MR-Egger回归法、中位数加权法(MW)、逆概率加权回归法(IVW)行TSMR分析,以P值评价胆囊切除术后和结直肠肛管恶性肿瘤发生风险之间的因果关系。结果 共筛选到32个与胆囊切除术相关的SNP。结果显示,胆囊切除术与盲肠癌之间无因果关系(OR=22.222,95%CI:6.280e-02,7.864e+03;P=0.300),与升结肠癌之间无因果关系(OR=3.176,95%CI:1.939e-03,5.204e+03;P=0.760),与横结肠癌之间无因果关系(OR=0.093,95%CI:6.683e-06,1.297e+03;P=0.626),与降结肠癌之间无因果关系(OR=0.093,95%CI:6.683e-06,1.297e+03;P=0.626),与乙状结肠癌之间无因果关系(OR=2.737,95%CI:4.24e-02,176.696;P=0.636),与直肠癌之间无因果关系(OR=0.306,95%CI:7.153e-03,13.099;P=0.537),与肛管癌之间无因果关系(OR=13.14,95%CI:6.683e-07,2.600e+06,P=0.764)。进一步的敏感性分析验证了上述关联的稳定性。结论 基于TSMR分析发现,无遗传证据支持胆囊切除与结直肠肛管恶性肿瘤发生风险具有相关性,即胆囊切除并不导致结直肠肛管恶性肿瘤的发生。

Objective To analyze the relationship between cholecystectomy and colorectal and anal cancers based on two-sample Mendelian randomization (TSMR).Methods The data of single nucleotide polymorphism (SNP) related to colorectal and anal cancers after cholecystectomy were obtained from open biological databases,and all retrieved data were analyzed based on genome-wide association studies (GWAS) database.The genetic loci closely associated with cholecystectomy were selected as instrumental variables.TSMR analysis was performed by using MR-Egger regression method,median weighted (MW) and inverse-variance weighted (IVW) methods,respectively.The causal relationship between cholecystectomy and the risk of colorectal and anal cancers was evaluated by P value.Results A total of 32 SNPs related to cholecystectomy were screened.There was no causal relationship between cholecystectomy and cecum cancer (OR=22.222,95%CI:6.280e-02,7.864e+03;P=0.300),no causal relationship between cholecystectomy and the ascending colon cancer (OR=3.176,95%CI:1.939e-03,5.204e+03;P=0.760),and no causal relationship between cholecystectomy and transverse colon cancer (OR=0.093,95%CI:6.683e-06,1.297e+03;P=0.626),and no causal relationship between cholecystectomy and the descending colon cancer (OR=0.093,95%CI:6.683e-06,1.297e+03;P=0.626),and no causal relationship between cholecystectomy and sigmoid colon cancer (OR=2.737,95%CI:4.24e-02,176.696;P=0.636),and no causal relationship between cholecystectomy and rectal cancer (OR=0.306,95%CI:7.153e-03,13.099;P=0.537),and no causal relationship between cholecystectomy and anal cancer (OR=13.14,95%CI:6.683e-07,2.600e+06,P=0.764),respectively.Subsequent sensitivity analysis confirmed the robustness of the correlation.Conclusions Based on TSMR analysis,there is no genetic evidence supporting the correlation between cholecystectomy and the risk of colorectal and anal cancers.Cholecystectomy does not lead to the incidence of colorectal and anal cancers.