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

doi:10.3877/cma.j.issn.2095-3232.2024.03.010

Abstract

Abstract:

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

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.

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Figures/Tables 3

References 35

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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

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

肿瘤名称	IVW		MR-Egger		MW		Q值
肿瘤名称	OR（95%CI）	P值	OR（95%CI）	P值	OR（95%CI）	P值	Q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

肿瘤名称	IVW		MR-Egger		MW		Q值
肿瘤名称	OR（95%CI）	P值	OR（95%CI）	P值	OR（95%CI）	P值	Q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

肿瘤名称	MR-Egger回归
肿瘤名称	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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