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中华普通外科学文献(电子版) ›› 2024, Vol. 18 ›› Issue (01) : 29 -33. doi: 10.3877/cma.j.issn.1674-0793.2024.01.005

论著

两样本孟德尔随机化分析阑尾切除与结直肠肛管恶性肿瘤发生风险的关系
牛斌, 饶兰英, 娜迪拉·哈孜肯尼, 何龙林, 刘晓晨, 蒋波()   
  1. 519000 珠海,中山大学附属第五医院胃肠外科
    519000 珠海市第三中学校医办公室
  • 收稿日期:2023-10-01 出版日期:2024-02-01
  • 通信作者: 蒋波

Causal relationship between appendicectomy and colorectal anal canal malignancy: A two-sample Mendelian randomization study

Bin Niu, Lanying Rao, Hazikenni Nadila·, Longlin He, Xiaochen Liu, Bo Jiang()   

  1. Department of Gastrointestinal Surgery, the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, China
    Medical Office of Zhuhai No.3 Middle School, Zhuhai 519000, China
  • Received:2023-10-01 Published:2024-02-01
  • Corresponding author: Bo Jiang
引用本文:

牛斌, 饶兰英, 娜迪拉·哈孜肯尼, 何龙林, 刘晓晨, 蒋波. 两样本孟德尔随机化分析阑尾切除与结直肠肛管恶性肿瘤发生风险的关系[J/OL]. 中华普通外科学文献(电子版), 2024, 18(01): 29-33.

Bin Niu, Lanying Rao, Hazikenni Nadila·, Longlin He, Xiaochen Liu, Bo Jiang. Causal relationship between appendicectomy and colorectal anal canal malignancy: A two-sample Mendelian randomization study[J/OL]. Chinese Archives of General Surgery(Electronic Edition), 2024, 18(01): 29-33.

目的

利用全基因组关联研究(GWAS)分析相关数据,通过两样本孟德尔随机化(MR)评估阑尾切除与结直肠肛管恶性肿瘤发生之间的因果关系。

方法

阑尾切除与结直肠肛管恶性肿瘤相关的单核苷酸多态性(SNP)数据来自英国生物数据库(UK Biobank)和GWAS catalog生物数据库,筛选与阑尾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、加权中位数法、逆方差加权法进行MR分析,以P值评价阑尾切除和结直肠肛管恶性肿瘤风险之间的因果关系。

结果

最终筛选出15个与阑尾切除相关的SNP位点作为最终工具变量,即rs106520、rs10829663、rs10849448、rs142069498、rs21525、rs2171591、rs224029、rs2326394、rs2780304、rs34236350、rs56259011、rs72827881、rs7649870、rs76896900、rs815430。以三种方法进行MR分析,皆显示P>0.05,阑尾切除与结直肠肛管恶性肿瘤之间没有因果关系,数据之间的异质性和总体多效性不明显。

结论

阑尾切除与结直肠肛管恶性肿瘤发生风险没有相关的遗传证据。

Objective

To reveal the causal association between appendicectomy and colorectal anal canal malignancies, by conducting a two-sample Mendelian randomization (MR) analysis using Genome Wide Association Study (GWAS).

Methods

The single nucleotide polymorphism (SNP) data associated with appendectomy and colorectal anal malignancies were obtained from publicly published biological databases such as UK Biobank and GWAS catalog, and all aggregated data based on GWAS were analyzed. Genetic loci closely associated with appendectomy were selected as instrumental variables. MR-Egger regression method, weighting median method, inverse variance weighting method were used to make two-sample MR, and P-value was used to evaluate the causal relationship between appendectomy and the risk of colorectal and anal canal malignancy.

Results

15 SNP loci related to appendicectomy were screened, including rs106520, rs10829663, rs10849448, rs142069498, rs21525, rs2171591, rs224029, rs2326394, rs2780304, rs34236350, rs56259011, rs72827881, rs7649870, rs76896900, rs815430. Three MR analysis methods revealed that there was no causal relationship between appendicectomy and colorectal anal canal malignancies. The heterogeneity and overall pleiotropy between data were not significant (P>0.05).

Conclusion

There is no causal relationship between appendicectomy and colorectal anal canal malignancies.

图1 孟德尔三大假设原理图 1.遗传变异与阑尾切除密切相关;2.遗传变异与结直肠肛管恶性肿瘤的其他混杂因素无关;3.遗传变异仅通过阑尾切除对结直肠恶性肿瘤和肛管恶性肿瘤起作用
表1 全基因组关联研究(GWAS)汇总数据
表2 MR-Egger回归法、WM法、IVW法的孟德尔随机化分析结果
表3 异质性、多效性和敏感性分析
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