Journal of Shandong University (Health Sciences) ›› 2025, Vol. 63 ›› Issue (2): 77-83.doi: 10.6040/j.issn.1671-7554.0.2024.0285

• Clinical Medicine • Previous Articles     Next Articles

A mendelian randomization study on the association between appendectomy and the risk of colorectal cancer

CHANG Yu1, HU Yunfeng1, WANG Huifeng2, GUO Jing1, ZHANG Tiao1, HAO Yaqin1, LIU Yu1   

  1. 1. Department of Radiotherapy;
    2. Department of Gastroenterology, Yanan University Affiliated Hospital, Yanan 716000, Shaanxi, China
  • Online:2025-03-10 Published:2025-03-07

PDF (PC)

22

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

CLC Number: 

  • R735.34
[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.
[1] YANG Hui, SU Shijing, LI Fen. Study on the causal relationship between cathepsins and risk of frailty based on bidirectional two-sample Mendelian randomization [J]. Journal of Shandong University (Health Sciences), 2025, 63(2): 67-76.
[2] CUI Qianqian, LI Jinpeng, WU Yudan, HOU Zhiping, SUN Weiluo, CUI Panpan, HE Peiyuan. Clinical value of fecal miRNA for non-invasive screening of advanced colorectal adenomas [J]. Journal of Shandong University (Health Sciences), 2025, 63(2): 43-50.
[3] WANG Gang, XU Pengyan, ZHAO Xuan, WANG Haifeng, GE Miaomiao, PAN Huafeng, JIANG Zhiwei. Effect of ω-3 polyunsaturated fatty acids on recovery of autonomic nervous system and intestinal function after laparoscopic colorectal cancer surgery [J]. Journal of Shandong University (Health Sciences), 2025, 63(2): 36-42.
[4] YUAN Zonghuai, PAN Guangye, CHI Yuemei, AN Chuanguo, ZHANG Yonggang. Causal relationship between low grade serous ovarian cancer and breast cancer analyzed by Mendelian randomization [J]. Journal of Shandong University (Health Sciences), 2025, 63(1): 99-107.
[5] ZHANG Zhan, LI Jianfeng, LI Yanling, WANG Bowen, ANGWEN Chenglinlongzhu, WANG Xin, ZHANG Xiaoming, XIE Ping. Mendelian randomization analysis of causality between dietary factors and preeclampsia [J]. Journal of Shandong University (Health Sciences), 2024, 62(8): 59-66.
[6] FENG Yue, YU Yifan, WU Sijia, LI Hongkai, XUE Fuzhong. Mendelian randomization study of visceral adipose tissue and lung diseases [J]. Journal of Shandong University (Health Sciences), 2024, 62(7): 48-55.
[7] WANG Xiao, KONG Wenru, CUI Weiliang, WANG Shuqi. Alstonia mairei total alkaloids enhance the sensitivity of colorectal cancer to 5-fluorouracil chemotherapy [J]. Journal of Shandong University (Health Sciences), 2024, 62(6): 30-37.
[8] WEI Yanruoxue, LI Ziqi, LIU Chuncheng, LIU Xiaohan, ZHAO Ran, LIU Yukun. Intratumor heterogeneity of SP1 expression in colorectal cancer and its clinical significance [J]. Journal of Shandong University (Health Sciences), 2024, 62(5): 89-94.
[9] WU Tong, YANG Jingyu, LIN Dang, XU Wanru, ZENG Yujun. Genetic association of lipids and lipid-lowering drugs with chronic obstructive pulmonary disease based on Mendelian randomization [J]. Journal of Shandong University (Health Sciences), 2024, 62(5): 54-63.
[10] LIU Chuncheng, LIU Xiaohan, WEI Yanruoxue, LI Ziqi, LIU Yukun, ZHAO Ran. Subcellular localization pattern of bromodomain containing 9 in colorectal cancer and its clinical significance [J]. Journal of Shandong University (Health Sciences), 2024, 62(4): 24-30.
[11] WU Fei, LI Qingli, XIAO Zhenwei. Causal association between cytokines and chronic kidney disease based on Mendelian randomization [J]. Journal of Shandong University (Health Sciences), 2024, 62(11): 85-95.
[12] YU Li, WANG Yijia, YANG Yong, LIU Xuehuan, WAN Xuehua, BAO Cuiping, MIAO Beiliang, LI Siqi, LI Jing, LIU Jun. Relationship between fusobacterium nucleatum mediated autophagy and cell refractive index based on optical surface wave [J]. Journal of Shandong University (Health Sciences), 2024, 62(10): 87-97.
[13] JING Kai, XU Zhiwei, LI Leping. Exploring colorectal cancer related genes and their functions based on GEO [J]. Journal of Shandong University (Health Sciences), 2024, 62(1): 21-30.
[14] DONG Yaqi, WANG Xinhui, ZHAO Yinghui, WANG Chuanxin. Clinical value of serum exosomal LINC02163 as a marker for distant metastasis of colorectal cancer [J]. Journal of Shandong University (Health Sciences), 2023, 61(9): 19-28.
[15] ZHANG Nana, ZHAO Yiming, LIU Xinmin. Causal relationship between uterine leiomyomas and breast cancer: a two-sample Mendelian randomization study [J]. Journal of Shandong University (Health Sciences), 2023, 61(8): 86-93.
Viewed
Full text
22
HTML PDF
Just accepted Online first Issue Just accepted Online first Issue
0 0 0 0 0 22

  From local
  Times 22
  Rate 100%

Abstract
58
Just accepted Online first Issue
0 0 58
  From Others local
  Times 56 2
  Rate 97% 3%

Cited
Web of Science  Crossref   ScienceDirect  Search for Citations in Google Scholar >>
 
This page requires you have already subscribed to WoS.
  Shared   
  Discussed   
No Suggested Reading articles found!
Copyright 2018 © Editorial office of Journal of Shandong University (Health Sciences)
Supported by Beijing Magtech Co.Ltd