您的位置：山东大学 -> 科技期刊社 -> 《山东大学学报（医学版）》

山东大学学报 (医学版) ›› 2023, Vol. 61 ›› Issue (10): 58-62.doi: 10.6040/j.issn.1671-7554.0.2023.0451

• • 上一篇    下一篇

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

常鑫1,2,刘世佳1,2,韩璐2   

  1. 1.大连医科大学研究生院, 辽宁 大连 116044;2. 大连市妇女儿童医疗中心(集团)妇科 辽宁省妇女儿童恶性肿瘤早期诊断与生物治疗重点实验室 国家妇产科临床重点专科建设项目, 辽宁 大连116033
  • 发布日期:2023-11-08
  • 通讯作者: 韩璐. E-mail:13940801858@163.com

A Mendelian randomization study of aspirin use and the risk of endometrial cancer

CHANG Xin1,2, LIU Shijia1,2, HAN Lu2   

  1. 1. Graduate School of Dalian Medical University, Dalian 116044, Liaoning, China;
    2. Department of Gynecology, Dalian Women and Childrens Medical Centre(Group)/ Laboratory of Early Diagnosis and Biotherapy of Malignant Tumors in Children and Women in Liaoning Province/ National Clinical Key Specialist Construction Project of Obstetrics and Gynecology, Dalian 116033, Liaoning, China
  • Published:2023-11-08

PDF (PC)

249

摘要： 目的 利用两样本孟德尔随机化研究方法,探讨服用阿司匹林与子宫内膜癌发病风险间的因果关系。 方法 进行两样本孟德尔随机化分析,利用人类全基因组关联分析(GWAS)计算服用阿司匹林和子宫内膜样癌(EEC)及非子宫内膜样癌(NEC)发病风险之间的潜在因果关系。其中服用阿司匹林和EEC、NEC相关的单核苷酸多态性(SNP)数据均来自于GWAS catalog数据库。选择与服用阿司匹林强关联的SNPs作为工具变量,并借助逆方差加权法(IVW)、加权中位数法、MR Egger、简单模型、加权模型等多种统计学方法,以比值比(OR)评价服用阿司匹林与EEC及NEC风险之间的因果关系。 结果 共纳入6个SNP作为工具变量,IVW方法显示服用阿司匹林可降低EEC的发病风险(OR=0.02,95%CI:0~0.28, P=0.005),而服用阿司匹林与NEC的发病风险之间无类似的因果关系(OR=0.00,95%CI:0.00~16.26, P=0.199)。另外几种统计学方法的结果与IVW方法显示的结果一致。敏感性分析表明,在对两类组织类型子宫内膜癌的研究中,异质性、水平多效性及留一法检验均显示工具变量的可靠性,无明显偏倚。 结论 服用阿司匹林可降低EEC的发病风险,通过更深层次探讨阿司匹林对EEC的生物学机制,有望对子宫内膜癌的早期防治产生重要影响。

关键词: 阿司匹林, 子宫内膜样癌, 非子宫内膜样癌, 孟德尔随机化, 因果推断

Abstract: Objective To investigate the causal relationship between aspirin use and the risk of endometrial cancer using the two-sample Mendelian randomization method. Methods A two-sample Mendelian randomization analysis was performed to estimate the potential causal relationship between aspirin use and endometrial endometrioid carcinoma(EEC)and non-endometrioid carcinoma(NEC)using GWAS genome-wide data. The single nucleotide polymorphism(SNP)data associated with aspirin use, EEC and NEC were obtained from the GWAS catalog database. SNPs with strong association with aspirin use were selected as instrumental variables and analyzed with inverse variance weighted(IVW), weighted median, MR Egger, simple mode and weighted mode. The causal relationship between aspirin use and risk of EEC and NEC was evaluated with odds ratio(OR). Results A total of 6 SNPs were included as instrumental variables, and the IVW showed that aspirin administration reduced the incidence of EEC(OR=0.02, 95%CI: 0-0.28, P=0.005), while no causal relationship was found between aspirin use and the risk of NEC(OR=0.00, 95%CI: 0.00-16.26, P=0.199). The results of other methods were consistent with those shown by IVW. Sensitivity analysis indicated that heterogeneity, horizontal pleiotropy and leave-one-out tests showed reliability of instrumental variables in different tissue types of endometrial cancer with no significant bias in the results. Conclusion Aspirin can reduce the risk of EEC. Exploring the biological mechanism of aspirin on EEC at a deeper level has important implications for the early prevention and treatment of endometrial cancer.

Key words: Aspirin, Endometrial cancer, Endometrial endometrioid carcinoma, Mendelian randomization, Causal inference

中图分类号: 

  • R737.33
[1] Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries [J]. CA Cancer J Clin, 2021, 71(3): 209-249.
[2] Dossus L, Lukanova A, Rinaldi S, et al. Hormonal, metabolic, and inflammatory profiles and endometrial cancer risk within the EPIC cohort—a factor analysis [J]. Am J Epidemiol, 2013, 177(8): 787-799.
[3] Huang X, Wang X, Shang J, et al. Estrogen related receptor alpha triggers the migration and invasion of endometrial cancer cells via up regulation of TGFB1 [J]. Cell Adhes Migr, 2018, 12(6): 538-547.
[4] Ricciotti E, FitzGerald GA. Aspirin in the prevention of cardiovascular disease and cancer [J]. Annu Rev Med, 2021, 72: 473-495. doi: 10.1146/annurev-med-051019-102940.
[5] Burgess S, Scott RA, Timpson NJ, et al. Using published data in Mendelian randomization: a blueprint for efficient identification of causal risk factors [J]. Eur J Epidemiol, 2015, 30(7): 543-552.
[6] OMara TA, Glubb DM, Amant F, et al. Identification of nine new susceptibility loci for endometrial cancer [J]. Nat Commun, 2018, 9(1): 3166.
[7] Boggs JM, Beck A, Ritzwoller DP, et al. A quasi-experimental analysis of lethal means assessment and risk for subsequent suicide attempts and deaths [J]. J Gen Intern Med, 2020, 35(6): 1709-1714.
[8] Davey Smith G, Hemani G. Mendelian randomization: genetic anchors for causal inference in epidemiological studies [J]. Hum Mol Genet, 2014, 23(R1): 89-98.
[9] Urbute A, Frederiksen K, Kjaer SK. Early adulthood overweight and obesity and risk of premenopausal ovarian cancer, and premenopausal breast cancer including receptor status: prospective cohort study of nearly 500, 000 Danish women [J]. Ann Epidemiol, 2022, 70: 61-67. doi: 10.1016/j.annepidem.
[10] Wang Y, Zeng X, Tan J, et al. Diabetes mellitus and endometrial carcinoma: risk factors and etiological links [J]. Medicine(Baltimore), 2022, 101(34): 30299.
[11] Zhang H, Kong W, Han C, et al. Correlation of metabolic factors with endometrial atypical hyperplasia and endometrial cancer: development and assessment of a new predictive nomogram [J]. Cancer Manag Res, 2021, 13: 7937-7949. doi: 10.2147/CMAR.S335924.
[12] Burgess S, Butterworth A, Thompson SG. Mendelian randomization analysis with multiple genetic variants using summarized data [J]. Genet Epidemiol, 2013, 37(7): 658-665.
[13] 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.
[14] 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.
[15] Chen X, Kong J, Diao X, et al. Depression and prostate cancer risk: a Mendelian randomization study [J]. Cancer Med, 2020, 9(23): 9160-9167.
[16] Bowden J, Spiller W, Del Greco MF, et al. Improving the visualization, interpretation and analysis of two-sample summary data Mendelian randomization via the Radial plot and Radial regression [J]. Int J Epidemiol, 2018, 47(4): 1264-1278.
[17] Burgess S, Thompson SG. Interpreting findings from Mendelian randomization using the MR-Egger method [J]. Eur J Epidemiol, 2017, 32(5): 377-389.
[18] Burgess S, Butterworth A, Thompson SG. Mendelian randomization analysis with multiple genetic variants using summarized data [J]. Genet Epidemiol, 2013, 37(7): 658-665.
[19] Matsuo K, Cahoon SS, Yoshihara K, et al. Association of low-dose aspirin and survival of women with endometrial cancer [J]. Obstet Gynecol, 2016, 128(1): 127-137.
[20] Webb PM, Na R, Weiderpass E, et al. Use of aspirin, other nonsteroidal anti-inflammatory drugs and acetaminophen and risk of endometrial cancer: the epidemiology of endometrial cancer consortium [J]. Ann Oncol, 2019, 30(2): 310-316.
[21] Matsuzaki S, Miller H, Takiuchi T, et al. Effects of aspirin and statin use on venous thromboembolism prophylaxis and survival in patients with endometrial cancer [J]. Expert Opin Drug Saf, 2022, 21(3): 335-347.
[22] Kastrinos F, Stoffel EM. History, genetics, and strategies for cancer prevention in Lynch syndrome [J]. Clin Gastroenterol Hepatol, 2014, 12(5): 715-727.
[23] 马珂, 杨曦, 杨子慧, 等. 子宫内膜癌相关林奇综合征筛查方法的研究[J]. 实用妇产科杂志, 2023, 39(1): 51-55. MA Ke, YANG Xi, YANG Zihui, et al. Study of screening methods for lynch syndrome in patients with endometrial carcinoma [J]. Journal of Practical Obstetrics and Gynecology, 2023, 39(1): 51-55.
[24] Burn J, Gerdes AM, MacRae F, et al. Long-term effect of aspirin on cancer risk in carriers of hereditary colorectal cancer: an analysis from the CAPP2 randomised controlled trial [J]. Lancet, 2011, 378(9809): 2081-2087.
[25] Movahedi M, Bishop DT, Macrae F, et al. Obesity, aspirin, and risk of colorectal cancer in carriers of hereditary colorectal cancer: a prospective investigation in the CAPP2 study [J]. J Clin Oncol, 2015, 33(31): 3591-3597.
[26] Deng L, Liang H, Han Y. Cyclooxygenase-2 and β-Catenin as potential diagnostic and prognostic markers in endometrial cancer [J]. Front Oncol, 2020, 10: 56. doi: 10.3389/fonc.2020.00056.
[27] Rothwell PM, Wilson M, Price JF, et al. Effect of daily aspirin on risk of cancer metastasis: a study of incident cancers during randomised controlled trials [J]. Lancet, 2012, 379(9826): 1591-1601.
[28] Jackson SS, Pfeiffer RM, Liu Z, et al. Association between aspirin use and biliary tract cancer survival [J]. JAMA Oncol, 2019, 5(12): 1802-1804.
[29] Elwood PC, Morgan G, Pickering JE, et al. Aspirin in the treatment of cancer: reductions in metastatic spread and in mortality: a systematic review and meta-analyses of published studies [J]. PLoS One, 2016, 11(4): e0152402.
[1] 张娜娜,赵一鸣,刘新敏. 基于两样本孟德尔随机化探索子宫肌瘤与乳腺癌的因果关系[J]. 山东大学学报 (医学版), 2023, 61(8): 86-93.
[2] 张天鑫,张婷,黄鑫,韩佳沂,王淑康. 氨基酸与2型糖尿病因果关系的孟德尔随机化分析[J]. 山东大学学报 (医学版), 2023, 61(5): 102-107.
[3] 张凯,司书成,李吉庆,刘晓雯,赵英琪,薛付忠. 睡眠性状与肠易激综合征的孟德尔随机化研究[J]. 山东大学学报 (医学版), 2022, 60(8): 109-114.
[4] 杨璇,李岩志,马伟,贾崇奇. 基于两样本孟德尔随机化的肺功能与新型冠状病毒肺炎病死风险的因果关系[J]. 山东大学学报 (医学版), 2021, 59(7): 104-111.
[5] 李云霞,李洪凯,马韫韬,于媛媛,孙晓茹,刘新辉, 司书成,侯蕾,袁同慧,刘璐,李文超,薛付忠,刘言训. 基于两样本孟德尔随机化的身高和冠心病风险之间因果关系[J]. 山东大学学报 (医学版), 2020, 58(5): 107-114.
[6] 刘新辉,李洪凯,李明卓,于媛媛,司书成,侯蕾,刘璐,李文超,袁同慧,李云霞,周宇畅,薛付忠. 腰围和冠心病因果关系的孟德尔随机化研究[J]. 山东大学学报 (医学版), 2019, 57(11): 103-109.
[7] 王建丽1，张涌2，朱媛媛3，李彬2，管益超1，耿婷4. 急性脑梗死患者阿司匹林抵抗与血小板miR126的相关性[J]. 山东大学学报（医学版）, 2014, 52(5): 77-81.
[8] 张晓月1,2，张维东1，王兆朋1，王朝霞1，张月英1，贾青1. 阿司匹林对小鼠S180肉瘤生长及血管和淋巴管生成的影响[J]. 山东大学学报(医学版), 2013, 51(1): 1-.
[9] 陈丽君1，尚慧5，罗霞1，王谦2，张建平3，王立祥4. 阿司匹林对小鼠子痫前期防治效果的研究[J]. 山东大学学报(医学版), 2011, 49(11): 53-.
[10] 周慧1,于宗琴2,李军3,李刚1,纪洪生1. 三种镇静催眠药对阿司匹林酯酶活性的影响[J]. 山东大学学报(医学版), 2010, 48(4): 151-.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
[1] 索东阳,申飞,郭皓,刘力畅,杨惠敏,杨向东. Tim-3在药物性急性肾损伤动物模型中的表达及作用机制[J]. 山东大学学报 (医学版), 2020, 1(7): 1 -6 .
[2] 马青源,蒲沛东,韩飞,王超,朱洲均,王维山,史晨辉. miR-27b-3p调控SMAD1对骨肉瘤细胞增殖、迁移和侵袭作用的影响[J]. 山东大学学报 (医学版), 2020, 1(7): 32 -37 .
[3] 张宝文,雷香丽,李瑾娜,罗湘俊,邹容. miR-21-5p靶向调控TIMP3抑制2型糖尿病肾病小鼠肾脏系膜细胞增殖及细胞外基质堆积[J]. 山东大学学报 (医学版), 2020, 1(7): 7 -14 .
[4] 付洁琦,张曼,张晓璐,李卉,陈红. Toll样受体4抑制过氧化物酶体增殖物激活受体γ加重血脂蓄积的分子机制[J]. 山东大学学报 (医学版), 2020, 1(7): 24 -31 .
[5] 龙婷婷,谢明,周璐,朱俊德. Noggin蛋白对小鼠脑缺血再灌注损伤后学习和记忆能力与齿状回结构的影响[J]. 山东大学学报 (医学版), 2020, 1(7): 15 -23 .
[6] 李宁,李娟,谢艳,李培龙,王允山,杜鲁涛,王传新. 长链非编码RNA AL109955.1在80例结直肠癌组织中的表达及对细胞增殖与迁移侵袭的影响[J]. 山东大学学报 (医学版), 2020, 1(7): 38 -46 .
[7] 徐玉香,刘煜东,张蓬,段瑞生. 101例脑小血管病患者脑微出血危险因素的回顾性分析[J]. 山东大学学报 (医学版), 2020, 1(7): 67 -71 .
[8] 丁祥云,于清梅,张文芳,庄园,郝晶. 胰岛素样生长因子II在84例多囊卵巢综合征患者颗粒细胞中的表达和促排卵结局的相关性[J]. 山东大学学报 (医学版), 2020, 1(7): 60 -66 .
[9] 肖娟,肖强,丛伟,李婷,丁守銮,张媛,邵纯纯,吴梅,刘佳宁,贾红英. 两种甲状腺超声数据报告系统诊断效能的比较[J]. 山东大学学报 (医学版), 2020, 1(7): 53 -59 .
[10] 史爽,李娟,米琦,王允山,杜鲁涛,王传新. 胃癌miRNAs预后风险评分模型的构建与应用[J]. 山东大学学报 (医学版), 2020, 1(7): 47 -52 .
版权所有 © 2018 《山东大学学报(医学版)》编辑部　
地址:山东大学科技期刊社（济南市历城区山大南路27号山东大学中心校区明德楼B座721室） 电话: 0531-88366918 E-mail: xbyxb@sdu.edu.cn
本系统由北京玛格泰克科技发展有限公司设计开发