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中华肝脏外科手术学电子杂志

中华肝脏外科手术学电子杂志 ›› 2024, Vol. 13 ›› Issue (03) : 313 -318. doi: 10.3877/cma.j.issn.2095-3232.2024.03.010

临床研究

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
牛斌1, 饶兰英2, 刘晓晨1, 何龙林1, 秦培鑫3,†()   
  1. 1. 519000　珠海，中山大学附属第五医院普通外科胃肠外科
    2. 519000　珠海市第三中学校医务室
    3. 519000　珠海，中山大学附属第五医院医学影像部放射科
  • 收稿日期:2024-01-30 出版日期:2024-06-10
  • 通信作者: 秦培鑫

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

Bin Niu1, Lanying Rao2, Xiaochen Liu1, Longlin He1, Peixin Qin3,†()   

  1. 1. Department of General Surgery, the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, China
    2. Infirmary, the Third Middle School of Zhuhai, Zhuhai 519000, China
    3. Department of Radiology, the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, China
  • Received:2024-01-30 Published:2024-06-10
  • Corresponding author: Peixin Qin
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牛斌, 饶兰英, 刘晓晨, 何龙林, 秦培鑫. 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[J]. 中华肝脏外科手术学电子杂志, 2024, 13(03): 313-318.

Bin Niu, Lanying Rao, Xiaochen Liu, Longlin He, Peixin Qin. Analysis of the relationship between cholecystectomy and colorectal and anal cancers based on Mendelian randomization[J]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2024, 13(03): 313-318.

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。

关键词: 两样本孟德尔随机化, 胆囊切除术, 结直肠肿瘤, 肛管恶性肿瘤
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.

Key words: Two sample Mendelian randomization, Cholecystectomy, Colorectal neoplasms, Anal canal neoplasms
表1 胆囊切除与结直肠肛管恶性肿瘤发生风险TSMR分析的GWAS数据库汇总数据
研究疾病类别 数据来源 研究时间以及研究人群 研究样本量 研究负责人
胆囊切除（ukb-b-6235） www.gwas.mrcieu.ac.uk/datasets/ukb-b-6235/ 2018 European 462 933 Ben Elsworth
盲肠恶性肿瘤（GCST90043848） www.ebi.ac.uk/gwas/studies/GCST90043848 2021 European 456 348 Jiang L
升结肠恶性肿瘤（GCST90043849） www.ebi.ac.uk/gwas/studies/GCST90043849 2021 European 456 348 Jiang L
横结肠恶性肿瘤（GCST90043851） www.ebi.ac.uk/gwas/studies/GCST90043851 2021 European 456 348 Jiang L
降结肠恶性肿瘤（GCST90043853） www.ebi.ac.uk/gwas/studies/GCST90043853 2021 European 456 348 Jiang L
乙状结肠恶性肿瘤（GCST90041895） www.ebi.ac.uk/gwas/studies/GCST90041895 2021 European 456 276 Jiang L
直肠恶性肿瘤（GCST90043857） www.ebi.ac.uk/gwas/studies/GCST90043857 2021 European 456 348 Jiang L
肛门及肛管恶性肿瘤（ANUS_ANALCANAL_EXALLC） finngen-public-data-r8/summary_stats 2021 European 259 669 FINN
表2 胆囊切除术与结直肠肛管恶性肿瘤发生风险的三种方法TSMR分析结果
肿瘤名称 IVW MR-Egger MW Q值
OR（95%CI） P值 OR（95%CI） P值 OR（95%CI） P值
盲肠恶性肿瘤（GCST90043848） 22.222（6.280e-02，7.864e+03） 0.300 1 973.007（1.083e-03，3.595e+09） 0.310 0.835 （1.692e-04，4.122e+03） 0.967 0.590
升结肠恶性肿瘤（GCST90043849） 3.176 （1.939e-03，5.204e+03） 0.760 3.029（3.818e-08，2.403e+08） 0.906 1.384 （2.452e-05，7.810e+04） 0.954 0.693
横结肠恶性肿瘤（GCST90043851） 0.093 （6.683e-06，1.297e+03） 0.626 0.041（2.701e-12 6.144e+08） 0.791 0.018 （3.675e-08，8.520e+03） 0.546 0.643
降结肠恶性肿瘤（GCST90043853） 0.093 （6.683e-06，1.297e+03） 0.626 0.041（2.701e-12，6.144e+08） 0.791 0.018 （2.063e-08，1.517e+04） 0.563 0.643
乙状结肠恶性肿瘤（GCST90041895） 2.737（4.240e-02，176.696） 0.636 1.196（3.646e-05，39228.782） 0.973 1.348（4.986e-03，364.541） 0.917 0.169
直肠恶性肿瘤（GCST90043857） 0.306（7.153e-03，13.099） 0.537 0.032（2.808e-06，361.130） 0.475 0.444（1.974e-03，99.832） 0.769 0.466
肛门及肛管恶性肿瘤（ANUS_ANALCANAL_EXALLC） 1.314e+01（6.638e-07，2.600e+08） 0.764 2.593e-04（4.648e-22，1.446e+14） 0.695 6.279e-03（3.454e-13 1.141e+08） 0.674 0.228
表3 胆囊切除术与结直肠肛管恶性肿瘤发生风险TSMR分析的水平多效性检验
肿瘤名称 MR-Egger回归
截距 P值
盲肠恶性肿瘤（GCST90043848） -0.021 322 780 0.509 353 6
升结肠恶性肿瘤（GCST90043849） 0.000 226 319 0.995 553 2
横结肠恶性肿瘤（GCST90043851） 0.003 928 496 0.940 173 3
降结肠恶性肿瘤（GCST90043853） 0.003 928 496 0.940 173 3
乙状结肠恶性肿瘤（GCST90041895） 0.003 934 165 0.865 466 3
直肠恶性肿瘤（GCST90043857） 0.010 754 020 0.606 754 3
肛门及肛管恶性肿瘤（ANUS_ANALCANAL_EXALLC） 0.051 553 590 0.572 048 3
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