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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

所属专题: 综述 临床研究

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
引用本文:

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/OL]. 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/OL]. 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。

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.

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
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
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
[1]
Soper NJ. Laparoscopic cholecystectomy[J]. Curr Probl Surg, 1991, 28(9):581-655.
[2]
Olsen DO. Laparoscopic cholecystectomy[J]. Am J Surg, 1991, 161(3):339-344.
[3]
Wood SG, Dai F, Dabu-Bondoc S, et al. Transvaginal cholecystectomy learning curve[J]. Surg Endosc, 2015, 29(7):1837-1841.
[4]
Choi YJ, Jin EH, Lim JH, et al. Increased risk of cancer after cholecystectomy: a nationwide cohort study in Korea including123, 295 patients[J]. Gut Liver, 2022, 16(3):465-473.
[5]
Yao Y, Li X, Xu B, et al. Cholecystectomy promotes colon carcinogenesis by activating the Wnt signaling pathway by increasing the deoxycholic acid level[J]. Cell Commun Signal, 2022, 20(1):71.
[6]
Doyle MT, Twomey CF, Owens TM, et al. Gastroesophageal reflux and tracheal contamination during laparoscopic cholecystectomy and diagnostic gynecological laparoscopy[J]. Anesth Analg, 1998, 86(3):624-628.
[7]
Boehme J, McKinley S, Michael Brunt L, et al. Patient comorbidities increase postoperative resource utilization after laparoscopic and open cholecystectomy[J]. Surg Endosc, 2016, 30(6):2217-2230.
[8]
Sallum RA, Padrão EM, Szachnowicz S, et al. Prevalence of gallstones in 1,229 patients submitted to surgical laparoscopic treatment of GERD and esophageal achalasia: associated cholecystectomy was a safe procedure[J]. Braz Arch Dig Surg, 2015, 28(2):113-116.
[9]
Katan MB. Apolipoprotein E isoforms, serum cholesterol, and cancer[J]. Lancet, 1986, 1(8479):507-508.
[10]
Emdin CA, Khera AV, Kathiresan S. Mendelian randomization[J]. JAMA, 2017, 318(19):1925-1926.
[11]
Hemani G, Zheng J, Elsworth B, et al. The MR-Base platform supports systematic causal inference across the human phenome[J]. Elife, 2018, 7: e34408.
[12]
Smith GD, Ebrahim S. Mendelian randomization: prospects, potentials, and limitations[J]. Int J Epidemiol, 2004, 33(1):30-42.
[13]
Lawlor DA, Harbord RM, Sterne JA, et al. Mendelian randomization: using genes as instruments for making causal inferences in epidemiology[J]. Stat Med, 2008, 27(8):1133-1163.
[14]
Burgess S, Davies NM, Thompson SG. Bias due to participant overlap in two-sample Mendelian randomization[J]. Genet Epidemiol, 2016, 40(7):597-608.
[15]
Bowden J, Davey Smith G, Burgess S. Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression[J]. Int J Epidemiol, 2015, 44(2):512-525.
[16]
Bowden J, Davey Smith G, Haycock PC, et al. Consistent estimation in Mendelian randomization with some invalid instruments using a weighted Median estimator[J]. Genet Epidemiol, 2016, 40(4):304-314.
[17]
Burgess S, Butterworth A, Thompson SG. Mendelian randomization analysis with multiple genetic variants using summarized data[J]. Genet Epidemiol, 2013, 37(7):658-665.
[18]
Verbanck M, Chen CY, Neale B, et al. Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases[J]. Nat Genet, 2018, 50(5):693-698.
[19]
Kamat MA, Blackshaw JA, Young R, et al. PhenoScanner V2: an expanded tool for searching human genotype-phenotype associations[J]. Bioinformatics, 2019, 35(22):4851-4853.
[20]
Bass RB, Teitelbaum EN. Novel advances in surgery for gallstone disease[J]. Curr Gastroenterol Rep, 2022, 24(7):89-98.
[21]
Williamson T, Song SE. Robotic surgery techniques to improve traditional laparoscopy[J]. JSLS, 2022, 26(2):e2022.00002.
[22]
Nix JT. Study of the relationship of environmental factors to the type and frequency of cancer causing death in nuns, 1963[J]. Hosp Prog, 1964, 45: 71-74.
[23]
Qin Q, Li W, Ren A, et al. Benign gallbladder disease is a risk factor for colorectal cancer, but cholecystectomy is not: a propensity score matching analysis[J]. Front Oncol, 2022, 12:1008394.
[24]
Sinha SR, Haileselassie Y, Nguyen LP, et al. Dysbiosis-induced secondary bile acid deficiency promotes intestinal inflammation[J]. Cell Host Microbe, 2020, 27(4):659-670, e5.
[25]
朱奎宇,张烨,孟庆洋, 等. 腹腔镜胆囊切除术是否会增加结直肠肿瘤患病风险?——系统性回顾及Meta分析[J]. 腹腔镜外科杂志, 2015, 20(12):925-930.
[26]
Sun Y, Yu M, Li D, et al. Asymptomatic chronic suppurative cholecystitis and peritonitis mimicking metastasis by 18F-FDGPET/CT scan during sigmoid colon cancer surveillance[J]. BJR Case Rep, 2022, 7(6):20210046.
[27]
Pang Y, Lv J, Kartsonaki C, et al. Causal effects of gallstone disease on risk of gastrointestinal cancer in Chinese[J]. Br J Cancer, 2021, 124(11):1864-1872.
[28]
Liu YL, Wu JS, Yang YC, et al. Gallbladder stones and gallbladder polyps associated with increased risk of colorectal adenoma in men[J]. J Gastroenterol Hepatol, 2018, 33(4):800-806.
[29]
Cai J, Zhao L, Li L, et al. Ultra-high-performance liquid chromatography-tandem mass spectrometry-based metabolomics unveils the metabolic alterations in colon cancer mice during CT-guided radiofrequency ablation[J]. Biomed Chromatogr, 2023, 37(8):e5658.
[30]
Aktan Ç, Tekin F, Oruç N, et al. CHRM3-associated miRNAs may play a role in bile acid-induced proliferation of H508 colon cancer cells[J]. Turk J Gastroenterol, 2023, 34(3):298-307.
[31]
Liu Y, Zhang S, Zhou W, et al. Secondary bile acids and tumorigenesis in colorectal cancer[J]. Front Oncol, 2022, 12: 813745.
[32]
Thomas JP, Modos D, Rushbrook SM, et al. The emerging role of bile acids in the pathogenesis of inflammatory bowel disease[J]. Front Immunol, 2022, 13: 829525.
[33]
Zeng H, Umar S, Rust B, et al. Secondary bile acids and short chain fatty acids in the colon: a focus on colonic microbiome, cell proliferation, inflammation, and cancer[J]. Int J Mol Sci, 2019, 20(5):1214.
[34]
Chen L, Fan Z, Sun X, et al. Associations of cholecystectomy with the risk of colorectal cancer: a Mendelian randomization study[J]. Chin Med J, 2023, 136(7):840-847.
[35]
Huyghe JR, Harrison TA, Bien SA, et al. Genetic architectures of proximal and distal colorectal cancer are partly distinct[J]. Gut, 2021, 70(7):1325-1334.
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