阑尾切除术与结直肠癌发病风险关联的孟德尔随机化研究

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doi:10.6040/j.issn.1671-7554.0.2024.0285

摘要： 目的采用两样本孟德尔随机化(mendelian randomization, MR)方法在遗传水平上探究阑尾切除术与结直肠癌之间的因果关系。方法采用逆方差加权法(inverse variance weighted, IVW)、MR Egger、加权中位数、简单模式和加权模式等方法进行分析。利用全基因组关联研究(genome-wide association study, GWAS)汇总数据,评估阑尾切除术与结直肠癌之间的因果关系。采用留一法、Cochrans Q检验,MR-Egger回归截距项检验、MR-PRESSO检验进行敏感性分析,评估工具变量的异质性、多效性和稳定性。结果随机效应 IVW 结果显示,阑尾切除术与结直肠癌无遗传因果关系(OR=1.13, 95%CI:0.29~4.36, P=0.86)。MR Egger、加权中位数、简单模式和加权模式的分析结果与随机效应 IVW 一致。无异质性、水平多效性。MR分析结果不受单个SNP的影响。结论阑尾切除术与结直肠癌在遗传水平上无因果关系。

关键词: 阑尾切除术, 结直肠癌, 孟德尔随机化, 遗传水平, 因果推断

Abstract: Objective To explore the causal relationship between appendectomy and colorectal cancer at the genetic level by a two-sample Mendelian randomization(MR). Methods The analysis was conducted using methods such as inverse variance weighting(IVW), MR Egger, weighted median, and both simple and weighted modes. Using summary data from genome-wide association studies(GWAS), the causal relationship between appendectomy and colorectal cancer was assessed. Sensitivity analyses were performed using leave-one-out analysis, Cochrans Q test, MR-Egger regression intercept test, and MR-PRESSO test to evaluate the heterogeneity, pleiotropy, and stability of the instrumental variables. Results The random-effects IVW results indicated that appendectomy hasd no genetic causal relationship with colorectal cancer(OR=1.13, 95%CI:0.29-4.36, P=0.86). The analysis results from MR Egger, weighted median, simple mode, and weighted mode were consistent with those of the random-effects IVW. There was no heterogeneity, horizontal pleiotropy. The MR analysis results were not influenced by any single SNP. Conclusion There is no causal relationship between appendectomy and colorectal cancer at the genetic level.

Key words: Appendectomy, Colorectal cancer, Mendelian randomization, Genetic level, Causal inference

中图分类号:

R735.34

常宇,胡云峰,王会丰,郭静,张跳,郝雅琴,刘雨. 阑尾切除术与结直肠癌发病风险关联的孟德尔随机化研究[J]. 山东大学学报 (医学版), 2025, 63(2): 77-83.

CHANG Yu, HU Yunfeng, WANG Huifeng, GUO Jing, ZHANG Tiao, HAO Yaqin, LIU Yu. A mendelian randomization study on the association between appendectomy and the risk of colorectal cancer[J]. Journal of Shandong University (Health Sciences), 2025, 63(2): 77-83.

[1]	Qu RZ, Ma YP, Zhang ZP, et al. Increasing burden of colorectal cancer in China[J]. Lancet Gastroenterol Hepatol, 2022, 7(8): 700.
[2]	Dekker E, Tanis PJ, Vleugels JLA, et al. Colorectal cancer[J]. Lancet, 2019, 394(10207): 1467-1480.
[3]	Vitetta L, Chen JZ, Clarke S. The vermiform appendix: an immunological organ sustaining a microbiome inoculum[J]. Clin Sci, 2019, 133(1): 1-8.
[4]	Constantin M, Petrescu L, Mătanie C, et al. The vermiform appendix and its pathologies[J]. Cancers, 2023, 15(15): 3872. https://doi.org/10.3390/cancers15153872.
[5]	Rothwell JA, Mori N, Artaud F, et al. Colorectal cancer risk following appendectomy: a Pooled analysis of three large ProsPective cohort studies[J]. Cancer Commun(Lond), 2022, 42(5): 486-489.
[6]	Liu Z, Ma X, Zhu C, et al. Risk of colorectal cancer after aPPendectomy: a systematic review and meta-analysis[J]. J Gastroenterol HePatol, 2023, 38(3): 350-358.
[7]	Wu SC, Chen WT, Muo CH, et al. Association between appendectomy and subsequent colorectal cancer development: an Asian population study[J]. PLoS One, 2015, 10(2): e0118411. doi:10.1371/journal.pone.0118411.
[8]	Shi F, Liu G, Lin Y, et al. Altered gut microbiome composition by appendectomy contributes to colorectal cancer[J]. Oncogene. 2023, 42(7): 530-540.
[9]	Yun Z, Guo Z, Li X, et al. Genetically predicted 486 blood metabolites in relation to risk of colorectal cancer: a Mendelian randomization study[J]. Cancer Med, 2023, 12(12): 13784-13799.
[10]	Suzuki S, Goto A, Nakatochi M, et al. Body mass index and colorectal cancer risk: a Mendelian randomization study[J]. Cancer Sci, 2021, 112(4): 1579-1588.
[11]	Wang L, Cao W, Xi MH, et al. Appendectomy and the risk of neurodegenerative diseases: a two-sample Mendelian randomization study[J]. Asian J Surg, 2023, 47(1): 673-674.
[12]	Lyon MS, Andrews SJ, Elsworth B, et al. The variant call format provides efficient and robust storage of GWAS summary statistics[J]. Genome Biol, 2021, 22(1): 32. doi:10.1186/s13059-020-02248-0.
[13]	Sakaue S, Kanai M, Tanigawa Y, et al. A cross-population atlas of genetic associations for 220 human phenotypes[J]. Nat Genet, 2021, 53(10): 1415-1424.
[14]	Li YW, Ye D, Zhou WK, et al. Alcohol consumption and colorectal cancer risk: a Mendelian randomization study[J]. Front Genet, 2022, 13: 967229. doi:10.3389/fgene.2022.967229.
[15]	常鑫, 刘世佳, 韩璐. 服用阿司匹林与子宫内膜癌发病风险的孟德尔随机化关系[J]. 山东大学学报(医学版), 2023, 61(10): 58-62, 82. CHANG Xin, LIU Shijia, HAN Lu. A Mendelian randomization study of aspirin use and the risk of endometrial cancer[J]. Journal of Shandong University(Health Sciences), 2023, 61(10): 58-62, 82.
[16]	Yang MY, Wan XJ, Zheng HS, et al. No evidence of a genetic causal relationship between ankylosing spondylitis and gut microbiota: a two-sample Mendelian randomization study[J]. Nutrients, 2023, 15(4): 1057. doi:10.3390/nu15041057.
[17]	Murphy N, Song MY, Papadimitriou N, et al. Associations between glycemic traits and colorectal cancer: a Mendelian randomization analysis[J]. J Natl Cancer Inst, 2022, 114(5): 740-752.
[18]	Cho YA, Lee J, Oh JH, et al. Genetic risk score, combined lifestyle factors and risk of colorectal cancer[J]. Cancer Res Treat, 2019, 51(3): 1033-1040.
[19]	OSullivan DE, Sutherland RL, Town S, et al. Risk factors for early-onset colorectal cancer: a systematic review and meta-analysis[J]. Clin Gastroenterol Hepatol, 2022, 20(6): 1229-1240.
[20]	Papadimitriou N, Bull CJ, Jenab M, et al. Separating the effects of early and later life adiposity on colorectal cancer risk: a Mendelian randomization study[J]. BMC Med, 2023, 21(1): 5. doi:10.1186/s12916-022-02702-9.
[21]	Sun J, Zhao J, Jiang F, et al. Identification of novel protein biomarkers and drug targets for colorectal cancer by integrating human Plasma Proteome with genome[J]. Genome Med, 2023, 15(1): 75. doi: 10.1186/s13073-023-01229-9.
[22]	Su YN, Hu YF, Xu YW, et al. Genetic causal relationship between age at menarche and benign oesophageal neoplasia identified by a Mendelian randomization study[J]. Front Endocrinol, 2023, 14: 1113765. doi:10.3389/fendo.2023.1113765.
[23]	Jung SY, Papp JC, Sobel EM, et al. Mendelian randomization study: the association between metabolic pathways and colorectal cancer risk[J]. Front Oncol, 2020, 10: 1005. doi: 10.3389/fonc.2020.01005.
[24]	Chan II, Kwok MK, Schooling CM. Blood pressure and risk of cancer: a Mendelian randomization study[J]. BMC Cancer, 2021, 21(1): 1338. doi:10.1186/s12885-021-09067-x.
[25]	Yuan S, Kar S, Carter P, et al. Is type 2 diabetes causally associated with cancer risk? evidence from a two-sample Mendelian randomization study[J]. Diabetes, 2020, 69(7): 1588-1596.
[26]	Xiong J, Yang L, Deng YQ, et al. The causal association between smoking, alcohol consumption and risk of bladder cancer: a univariable and multivariable Mendelian randomization study[J]. Int J Cancer, 2022, 151(12): 2136-2143.
[27]	Yuan S, Mason AM, Titova OE, et al. Morning chronotype and digestive tract cancers: Mendelian randomization study[J]. Int J Cancer, 2023, 152(4): 697-704.
[28]	Chen X, Kong JQ, Diao XY, et al. Depression and prostate cancer risk: a Mendelian randomization study[J]. Cancer Med, 2020, 9(23): 9160-9167.
[29]	Tan H, Wang SS, Huang FF, et al. Association between breast cancer and thyroid cancer risk: a two-sample Mendelian randomization study[J]. Front Endocrinol, 2023, 14: 1138149. doi:10.3389/fendo.2023.1138149.
[30]	Zhou X, Wang L, Xiao J, et al. Alcohol consumption, dna methylation and colorectal cancer risk: results from pooled cohort studies and mendelian randomization analysis[J]. Int J Cancer, 2022, 151(1): 83-94.
[31]	Chen JZ, Sali A, Vitetta L. The gallbladder and vermiform appendix influence the assemblage of intestinal microorganisms[J]. Future Microbiol, 2020, 15: 541-555. doi:10.2217/fmb-2019-0325.
[32]	Liang CS, Bai YM, Hsu JW, et al. The risk of Alzheimers disease after acute appendicitis with or without appendectomy[J]. J Am Med Dir Assoc, 2022, 23(4): 601-607.
[33]	Shi F, Liu G, Lin Y, et al. Altered gut microbiome composition by appendectomy contributes to colorectal cancer[J]. Oncogene, 2023, 42(7): 530-540.
[34]	高莹, 崔光星. 阑尾功能的再认识及急性阑尾炎的治疗进展[J]. 中国乡村医药, 2020, 27(18): 78-80. GAO Ying, CUI Guangxing. Re-understanding of appendix function and treatment progress of acute appendicitis[J]. Chinese Journal of Rural Medicine and Pharmacy, 2020, 27(18): 78-80.
[35]	Arjomand Fard N, Armstrong H, Perry T, et al. Appendix and ulcerative colitis: a key to explaining the pathogenesis and directing novel therapies?[J]. Inflamm Bowel Dis, 2023, 29(1): 151-160.
[36]	Quaglio AEV, Grillo TG, De Oliveira ECS, et al. Gut microbiota, inflammatory bowel disease and colorectal cancer[J]. World J Gastroenterol, 2022, 28(30): 4053-4060.
[37]	Cheng YW, Ling ZX, Li LJ. The intestinal microbiota and colorectal cancer[J]. Front Immunol, 2020, 11: 615056. doi:10.3389/fimmu.2020.615056.
[38]	Lin CZ, Cai XL, Zhang J, et al. Role of gut microbiota in the development and treatment of colorectal cancer[J]. Digestion, 2019, 100(1): 72-78.
[39]	Ka zmierczak-Siedlecka K, Daca A, Fic M, et al. Therapeutic methods of gut microbiota modification in colorectal cancer management- fecal microbiota transplantation, prebiotics, probiotics, and synbiotics[J]. Gut Microbes, 2020, 11(6): 1518-1530.

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