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) ›› 2025, Vol. 63 ›› Issue (12): 44-52.doi: 10.6040/j.issn.1671-7554.0.2024.1248

• 临床医学 • 上一篇    

东亚人肠道菌群与胰腺癌关系:基于孟德尔随机化方法的遗传学证据

杜凯豪1,侯立朝2,东小鸽1,薛伟伟1,何洁洁1,罗兰明慧1,蒋威1,汪占金1,王展2,3   

  1. 1.青海大学临床医学院, 青海 西宁 810016;2.青海大学附属医院肝胆胰外科, 青海 西宁 810001;3.青海大学附属医院医工结合与转化应用部, 青海 西宁 810001
  • 发布日期:2025-12-19
  • 通讯作者: 王展. E-mail:ufofu01@163.com
  • 基金资助:
    国家自然科学基金(82160131)

Relationship between gut microbiota and pancreatic cancer in East Asians: genetic evidence based on Mendelian randomization

DU Kaihao1, HOU Lizhao2, DONG Xiaoge1, XUE Weiwei1, HE Jiejie1, LUO Lanminghui1, JIANG Wei1, WANG Zhanjin1, WANG Zhan2,3   

  1. 1. Qinghai University Clinical Medical College, Xining 810016, Qinghai, China;;
    2. Department of Hepatopancreatobiliary Surgery, Affiliated Hospital of Qinghai University, Xining 810001, Qinghai, China;;
    3. Department of Medical Engineering Integration and Translational Application, Affiliated Hospital of Qinghai University, Xining 810001, Qinghai, China)
  • Published:2025-12-19

PDF (PC)

4

摘要： 目的 探讨东亚人群中肠道菌群(gut microbiota, GM)与胰腺癌(pancreatic cancer, PC)之间的因果关系,揭示PC的潜在病理机制,为临床干预提供理论依据。 方法 采用孟德尔随机化(Mendelian randomization, MR)分析方法,利用全基因组关联研究(genome-wide association studies, GWAS)数据库中的数据,以单核苷酸多态性作为工具变量,通过逆方差加权、加权中位数法、贝叶斯加权MR等多种MR方法评估析500种东亚人群GM与PC之间的因果关系。 结果 逆方差加权法结果显示,厄雷莫球菌属［日本生物银行(Biobank Japan, BBJ):OR=0.847,95%CI:0.734~0.978,P=0.024;欧洲生物信息研究所(European Bioinformatics Institute, EBI):OR=0.829,95%CI:0.727~0.945,P=0.005)］、鲍曼不动杆菌种(BBJ:OR=0.775,95%CI:0.667~0.900,P=0.001;EBI:OR=0.828,95%CI:0.731~0.937,P=0.003)、甲硫氨酸代谢途径I(MF0038)(BBJ:OR=0.299,95%CI:0.097~0.917,P=0.035;EBI:OR=0.260,95%CI:0.110~0.615,P=0.002)、螺杆菌属(BBJ:OR=0.771,95%CI:0.657~0.905,P=0.001;EBI:OR=0.807,95%CI:0.700~0.930,P=0.003)与PC的发生风险降低相关;阿姆尼普雷沃菌种(BBJ:OR=1.328,95%CI:1.086~1.623,P=0.006;EBI:OR=1.258,95%CI:1.041~1.520,P=0.018)、沙利特罗拟杆菌种(BBJ:OR=1.473,95%CI:1.150~1.887,P=0.002;EBI:OR=1.242,95%CI:1.030~1.497,P=0.023)、食酸菌属(BBJ:OR=1.184,95%CI:1.021~1.374,P=0.026;EBI:OR=1.166,95%CI:1.015~1.339,P=0.030)与PC的发生风险增加相关。贝叶斯加权MR结果显示,厄雷莫球菌属(BBJ:OR=0.844,95%CI:0.725~0.983,P=0.029;EBI:OR=0.825,95%CI:0.717~0.949,P=0.007)、鲍曼不动杆菌种(BBJ:OR=0.766,95%CI:0.647~0.906,P=0.002;EBI:OR=0.823,95%CI:0.720~0.939,P=0.004)、甲硫氨酸代谢途径I(MF0038)(BBJ:OR=0.270,95%CI:0.082~0.0888,P=0.031;EBI:OR=0.245,95%CI:0.098~0.610,P=0.003)、螺杆菌属(BBJ:OR=0.768,95%CI:0.647~0.912,P=0.003;EBI:OR=0.802,95%CI:0.689~0.934,P=0.004)与PC的发生风险降低相关;阿姆尼普雷沃菌种(BBJ:OR=1.340,95%CI:1.076~1.668,P=0.009;EBI:OR=1.262,95%CI:1.030~1.547,P=0.025)、沙利特罗拟杆菌种(BBJ:OR=1.487,95%CI:1.145~1.931,P=0.003;EBI:OR=1.256,95%CI:1.031~1.531,P=0.024)、食酸菌属(BBJ:OR=1.189,95%CI:1.017~1.390,P=0.029;EBI:OR=1.170,95%CI:1.011~1.353,P=0.036)与PC的发生风险增加相关。敏感性分析提示研究结果稳健。 结论 厄雷莫球菌属、鲍曼不动杆菌种、甲硫氨酸代谢途径I(MF0038)和螺杆菌属是PC的保护因素,而阿姆尼普雷沃菌种、沙利特罗拟杆菌种、食酸菌属会增加PC的发生风险。

关键词: 肠道菌群, 胰腺癌, 孟德尔随机化, 全基因组关联研究, 单核苷酸多态性

Abstract: Objective To explore the causal relationship between gut microbiota(GM)and pancreatic cancer(PC)in East Asians to reveal the potential pathological mechanisms of PC and provide a theoretical basis for clinical interventions. Methods Mendelian randomization(MR)analysis was conducted using data from genome-wide association studies(GWAS)databases to analyze the relationships between 500 gut microbiota features and PC in East Asians. Single nucleotide polymorphisms were used as instrumental variables, and various MR methods, including inverse variance weighting(IVW), weighted median method, and Bayesian weighted MR, were employed to assess the causal relationship between GM and PC. Results The results of the inverse-variance weighted method showed that g_Eremococcus ［Biobank Japan(BBJ): OR=0.847, 95%CI: 0.734-0.978, P=0.024; European Bioinformatics Institute(EBI): OR=0.829, 95%CI: 0.727-0.945, P=0.005), s_Acinetobacter_baumannii(BBJ: OR=0.775, 95%CI: 0.667-0.900, P=0.001; EBI: OR=0.828, 95%CI: 0.731-0.937, P=0.003), methionine metabolism I(MF0038)(BBJ: OR=0.299, 95%CI: 0.097-0.917, P=0.035; EBI: OR=0.260, 95%CI: 0.110-0.615, P=0.002), and g_Helicobacter(BBJ: OR=0.771, 95%CI: 0.657-0.905, P=0.001; EBI: OR=0.807, 95%CI: 0.700-0.930, P=0.003)were associated with a reduced risk of PC, whereas s_Prevotella_amnii(BBJ: OR=1.328, 95%CI: 1.086-1.623, P=0.006; EBI: OR=1.258, 95%CI: 1.041-1.520, P=0.018), s_Bacteroides_salanitronis(BBJ: OR=1.473, 95%CI: 1.150-1.887, P=0.002; EBI: OR=1.242, 95%CI: 1.030-1.497, P=0.023), and g_Acidovorax(BBJ: OR=1.184, 95%CI: 1.021-1.374, P=0.026; EBI: OR=1.166, 95%CI: 1.015-1.339, P=0.030)were associated with an increased risk of PC, and the results of the Bayesian weighted MR method similarly showed that g_Eremococcus(BBJ: OR=0.844, 95%CI: 0.725-0.983, P=0.029; EBI: OR=0.825, 95%CI: 0.717-0.949, P=0.007), s_Acinetobacter_baumannii(BBJ: OR=0.766, 95%CI: 0.647-0.906, P=0.002; EBI: OR=0.823, 95%CI: 0.720-0.939, P=0.004), methionine metabolism I(MF0038)(BBJ: OR=0.270, 95%CI: 0.082-0.888, P=0.031; EBI: OR=0.245, 95%CI: 0.098-0.610, P=0.003), and g_Helicobacter(BBJ: OR=0.768, 95%CI: 0.647-0.912, P=0.003; EBI: OR=0.802, 95%CI: 0.689-0.934, P=0.004)were associated with a reduced risk of PC, while s_Prevotella_amnii(BBJ: OR=1.340, 95%CI: 1.076-1.668, P=0.009; EBI: OR=1.262, 95%CI: 1.030-1.547, P=0.025), s_Bacteroides_salanitronis(BBJ: OR=1.487, 95%CI: 1.145-1.931, P=0.003; EBI: OR=1.256, 95%CI: 1.031-1.531, P=0.024), and g_Acidovorax(BBJ: OR=1.189, 95%CI: 1.017-1.390, P=0.029; EBI: OR=1.170, 95%CI: 1.011-1.353, P=0.036)were associated with an increased risk of PC. Sensitivity analyses suggested that the results were robust. Conclusion g_Eremococcus, s_Acinetobacter_baumannii, methionine metabolism pathway I(MF0038), and g_Helicobacter may serve as protective factors for PC, while s_Prevotella_amnii, s_Bacteroides_salanitronis, and g_Acidovorax may increase the risk of PC.

Key words: Gut microbiota, Pancreatic cancer, Mendelian randomization, Genome-wide association study, Single nucleotide polymorphisms

中图分类号: 

  • R735.9
[1] Zhan ZW, Zheng XH, Xu SH, et al. Rising burden of pancreatic cancer in China: trends, drivers, and future projections[J]. PLoS One, 2025, 20(7): e0327009. doi: 10.1371/journal.pone.0327009
[2] He Y, Zhou XL, Fan XQ, et al. Disease burden of pancreatic cancer - China, 1990-2019[J]. China CDC Wkly, 2022, 4(24): 527.
[3] 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.
[4] 国家卫生健康委办公厅. 胰腺癌诊疗指南(2022年版)[J]. 临床肝胆病杂志, 2022, 38(5): 1006-1030. General Office of National Health Commission. Standard for diagnosis and treatment of pancreatic cancer(2022 edition)[J]. Journal of Clinical Hepatology, 2022, 38(5): 1006-1030.
[5] Kolbeinsson HM, Chandana S, Wright GP, et al. Panc-reatic cancer: a review of current treatment and novel therapies[J]. J Invest Surg, 2023, 36(1): 2129884. doi: 10.1080/08941939.2022.2129884
[6] Tong Y, Gao HR, Qi QC, et al. High fat diet, gut microbiome and gastrointestinal cancer[J]. Theranostics, 2021, 11(12): 5889-5910.
[7] Cohen LJ, Cho JH, Gevers D, et al. Genetic factors and the intestinal microbiome guide development of microbe-based therapies for inflammatory bowel diseases[J]. Gastroenterology, 2019, 156(8): 2174-2189.
[8] Wong SH, Yu J. Gut microbiota in colorectal cancer: mechanisms of action and clinical applications[J]. Nat Rev Gastroenterol Hepatol, 2019, 16(11): 690-704.
[9] Yang QY, Zhang JH, Zhu Y. Potential roles of the gut microbiota in pancreatic carcinogenesis and therapeutics[J]. Front Cell Infect Microbiol, 2022, 12: 872019. doi: 10.3389/fcimb.2022.872019
[10] Sethi V, Kurtom S, Tarique M, et al. Gut microbiota promotes tumor growth in mice by modulating immune response[J]. Gastroenterology, 2018, 155(1): 33-37.
[11] Yu Q, Newsome RC, Beveridge M, et al. Intestinal microbiota modulates pancreatic carcinogenesis through intratumoral natural killer cells[J]. Gut Microbes, 2022, 14(1): 2112881. doi: 10.1080/19490976.2022.2112881
[12] Papa V, Schepis T, Coppola G, et al. The role of microbiota in pancreatic cancer[J]. Cancers(Basel), 2023, 15(12): 3143. doi: 10.3390/cancers15123143
[13] Jiang H, Song TJ, Li ZY, et al. Dissecting the association between gut microbiota and liver cancer in European and East Asian populations using Mendelian randomization analysis[J]. Front Microbiol, 2023, 14: 1255650. doi: 10.3389/fmicb.2023.1255650
[14] Yadav D, Ghosh TS, Mande SS. Global investigation of composition and interaction networks in gut microbiomes of individuals belonging to diverse geographies and age-groups[J]. Gut Pathog, 2016, 8: 17. doi: 10.1186/s13099-016-0099-z
[15] Syromyatnikov M, Nesterova E, Gladkikh M, et al. Characteristics of the gut bacterial composition in people of different nationalities and religions[J]. Microorga-nisms, 2022, 10(9): 1866. doi: 10.3390/microorganisms10091866
[16] 吴彤, 杨晶玉, 林盪, 等. 基于孟德尔随机化方法探讨脂质和降脂药物与慢性阻塞性肺病的遗传关联[J]. 山东大学学报(医学版), 2024, 62(5): 54-63. WU Tong, YANG Jingyu, LIN Dang, et al. 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.
[17] Burgess S, Dudbridge F, Thompson SG. Combining information on multiple instrumental variables in Mendelian randomization: comparison of allele score and summarized data methods[J]. Stat Med, 2016, 35(11): 1880-1906.
[18] 柴红强, 庞磊, 吴明, 等. 利用两样本孟德尔随机化方法探究茶摄入量与膀胱癌发病风险的因果关系[J]. 现代肿瘤医学, 2023, 31(18): 3450-3454. CHAI Hongqiang, PANG Lei, WU Ming, et al. Using two sample Mendelian randomization method to explore the causal relationship between tea intake and the risk of bladder cancer[J]. Journal of Modern Oncology, 2023, 31(18): 3450-3454.
[19] Liu XM, Tong X, Zou YQ, et al. Mendelian randomization analyses support causal relationships between blood metabolites and the gut microbiome[J]. Nat Genet, 2022, 54(1): 52-61.
[20] 张展, 李建锋, 李燕玲, 等. 饮食因素与子痫前期因果关系的孟德尔随机化分析[J]. 山东大学学报(医学版), 2024, 62(8): 59-66. ZHANG Zhan, LI Jianfeng, LI Yanling, et al. Mendelian randomization analysis of causality between dietary factors and preeclampsia[J]. Journal of Shandong University(Health Sciences), 2024, 62(8): 59-66.
[21] 吴飞, 李清丽, 肖振卫. 孟德尔随机化探究细胞因子与慢性肾脏病的因果关系[J]. 山东大学学报(医学版), 2024, 62(11): 85-95. 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.
[22] 冯悦, 俞一凡, 吴思佳, 等. 内脏脂肪组织与肺部疾病的孟德尔随机化研究[J]. 山东大学学报(医学版), 2024, 62(7): 48-55. FENG Yue, YU Yifan, WU Sijia, et al. Mendelian randomization study of visceral adipose tissue and lung diseases[J]. Journal of Shandong University(Health Sciences), 2024, 62(7): 48-55.
[23] Wang CD, Zhu DD, Zhang DJ, et al. Causal role of immune cells in schizophrenia: Mendelian randomization(MR)study[J]. BMC Psychiatry, 2023, 23(1): 590. doi: 10.1186/s12888-023-05081-4
[24] Pierce BL, Ahsan H, Vanderweele TJ. Power and instrument strength requirements for Mendelian randomization studies using multiple genetic variants[J]. Int J Epidemiol, 2011, 40(3): 740-752.
[25] 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.
[26] Zhao J, Ming JS, Hu XH, et al. Bayesian weighted Mendelian randomization for causal inference based on summary statistics[J]. Bioinformatics, 2020, 36(5): 1501-1508.
[27] Tempero MA, Malafa MP, Al-Hawary M, et al. Pancreatic adenocarcinoma, version 2.2021, NCCN clinical practice guidelines in oncology[J]. J Natl Compr Canc Netw, 2021, 19(4): 439-457.
[28] Seo MS, Yeo J, Hwang IC, et al. Risk of pancreatic cancer in patients with systemic lupus erythematosus: a meta-analysis[J]. Clin Rheumatol, 2019, 38(11): 3109-3116.
[29] Verbanck M, Chen CY, Neale B, et al. Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases[J]. Nat Genet, 2018, 50(5): 693-698.
[30] Wu FS, Huang Y, Hu JL, et al. Mendelian randomization study of inflammatory bowel disease and bone mineral density[J]. BMC Med, 2020, 18(1): 312. doi: 10.1186/s12916-020-01778-5
[31] Dong Y, Hu AQ, Han BX, et al. Mendelian randomization analysis reveals causal effects of blood lipidome on gestational diabetes mellitus[J]. Cardiovasc Diabetol, 2024, 23(1): 335. doi: 10.1186/s12933-024-02429-2
[32] Zhang TL, Cao YN, Zhao JQ, et al. Assessing the causal effect of genetically predicted metabolites and metabolic pathways on stroke[J]. J Transl Med, 2023, 21(1): 822. doi: 10.1186/s12967-023-04677-4
[33] Skrivankova VW, Richmond RC, Woolf BAR, et al. Strengthening the reporting of observational studies in epidemiology using Mendelian randomization: the STROBE-MR statement[J]. JAMA, 2021, 326(16): 1614-1621.
[34] Ertz-Archambault N, Keim P, Von Hoff D. Microbiome and pancreatic cancer: a comprehensive topic review of literature[J]. World J Gastroenterol, 2017, 23(10): 1899-1908.
[35] Hong JZ, Fu YF, Chen XQ, et al. Gut microbiome changes associated with chronic pancreatitis and pancreatic cancer: a systematic review and meta-analysis[J]. Int J Surg, 2024, 110(9): 5781-5794.
[36] Dickson I. Microbiome promotes pancreatic cancer[J]. Nat Rev Gastroenterol Hepatol, 2018, 15(6): 328. doi: 10.1038/s41575-018-0013-x
[37] Attebury H, Daley D. The gut microbiome and pancreatic cancer development and treatment[J]. Cancer J, 2023, 29(2): 49-56.
[38] Zhou CF, Xu XJ. Causal relationship between gut microbiota and pancreatic cancer: a two-sample Mendelian randomisation study[J]. Ann Pancreat Cancer, 2024, 7: 1. doi: 10.21037/apc-23-15
[39] Zhang ZL, Zhang H, Chen T, et al. Regulatory role of short-chain fatty acids in inflammatory bowel disease[J]. Cell Commun Signal, 2022, 20(1): 64. doi: 10.1186/s12964-022-00869-5
[40] Liu HY, Lu HD, Wang YX, et al. Unlocking the power of short-chain fatty acids in ameliorating intestinal mucosal immunity: a new porcine nutritional approach[J]. Front Cell Infect Microbiol, 2024, 14: 1449030. doi: 10.3389/fcimb.2024.1449030
[41] Li QX, Jin M, Liu YH, et al. Gut microbiota: its potential roles in pancreatic cancer[J]. Front Cell Infect Microbiol, 2020, 10: 572492. doi: 10.3389/fcimb.2020.572492
[42] Raderer M, Wrba F, Kornek G, et al. Association between Helicobacter pylori infection and pancreatic cancer[J]. Oncology, 1998, 55(1): 16-19.
[43] Kosunen TU, Pukkala E, Sarna S, et al. Gastric cancers in Finnish patients after cure of Helicobacter pylori infection: a cohort study[J]. Int J Cancer, 2011, 128(2): 433-439.
[44] 窦逾常, 王江滨. 胰腺癌患者幽门螺杆菌感染的检测及临床意义[J]. 吉林大学学报(医学版), 2008, 34(2): 317-319. DOU Yuchang, WANG Jiangbin. Detection of H. pylori infection in patients with pancreatic cancer and clinical significance[J]. Journal of Jilin University(Medicine Edition), 2008, 34(2): 317-319.
[45] Lindkvist B, Johansen D, Borgström A, et al. A prospective study of Helicobacter pylori in relation to the risk for pancreatic cancer[J]. BMC Cancer, 2008, 8: 321. doi: 10.1186/1471-2407-8-321
[46] Rundle A, Ahsan H, Vineis P. Better cancer biomarker discovery through better study design[J]. Eur J Clin Invest, 2012, 42(12): 1350-1359.
[47] Risch HA, Lu LG, Kidd MS, et al. Helicobacter pylori seropositivities and risk of pancreatic carcinoma[J]. Cancer Epidemiol Biomarkers Prev, 2014, 23(1): 172-178.
[48] Wang Y, Zhang FC, Wang YJ. Helicobacter pylori and pancreatic cancer risk: a meta-analysis based on 2, 049 cases and 2, 861 controls[J]. Asian Pac J Cancer Prev, 2014, 15(11): 4449-4454.
[49] Wong-Rolle A, Wei HK, Zhao C, et al. Unexpected guests in the tumor microenvironment: microbiome in cancer[J]. Protein Cell, 2021, 12(5): 426-435.
[50] Gao F, Yu B, Rao BC, et al. The effect of the intratumoral microbiome on tumor occurrence, progression, prognosis and treatment[J]. Front Immunol, 2022, 13: 1051987.
[51] Tabrizi E, Pourteymour Fard Tabrizi F, Mahmoud Khaled G, et al. Unraveling the gut microbiomes contribution to pancreatic ductal adenocarcinoma: mechanistic insights and therapeutic perspectives[J]. Front Immunol, 2024, 15: 1434771.
[52] Marino A, Augello E, Stracquadanio S, et al. Unveiling the secrets of Acinetobacter baumannii: resistance, current treatments, and future innovations[J]. Int J Mol Sci, 2024, 25(13): 6814. doi: 10.3390/ijms25136814
[53] Shi JC, Cheng JH, Liu SR, et al. Acinetobacter baumannii: an evolving and cunning opponent[J]. Front Microbiol, 2024, 15: 1332108. doi: 10.3389/fmicb.2024.1332108
[54] Mohamed EA, Raafat MM, Samir Mohamed R, et al. Acinetobacter baumannii biofilm and its potential therapeutic targets[J]. Future J Pharm Sci, 2023, 9(1): 82. doi: 10.1186/s43094-023-00525-w
[55] Jeffreys S, Chambers JP, Yu JJ, et al. Insights into Acinetobacter baumannii protective immunity[J]. Front Immunol, 2022, 13: 1070424. doi: 10.3389/fimmu.2022.1070424
[56] Sanderson SM, Gao X, Dai ZW, et al. Methionine metabolism in health and cancer: a nexus of diet and precision medicine[J]. Nat Rev Cancer, 2019, 19(11): 625-637.
[57] Gao X, Sanderson SM, Dai ZW, et al. Dietary methionine influences therapy in mouse cancer models and alters human metabolism[J]. Nature, 2019, 572(7769): 397-401.
[58] Richie JP Jr, Sinha R, Dong Z, et al. Dietary methionine and total sulfur amino acid restriction in healthy adults[J]. J Nutr Health Aging, 2023, 27(2): 111-123.
[1] 葛丽娟 金瑞峰 王纪文 许新升 李癊. 多药耐药基因1 C1236T多态性与癫痫患者对药物反应性的相关性[J]. 山东大学学报(医学版), 2209, 47(6): 99-102.
[2] 王乐,罗清馨,吴思佳,吴雨桐,葛祎蕾,俞一凡,韦云,吉寒冰,刘铁梅,张紫妍,修佳伟,薛付忠,李洪凯. 虚弱和癫痫关联研究:前瞻性队列和孟德尔随机化分析[J]. 山东大学学报 (医学版), 2025, 63(9): 20-30.
[3] 王雪梅,杨豪,宋洋,程世超,张婷婷,王艳春. 抗糖尿病药物与女性恶性肿瘤的因果关联:一项两样本孟德尔随机化分析[J]. 山东大学学报 (医学版), 2025, 63(6): 67-77.
[4] 祝永才,谢艳,齐秋晨,李培龙,王传新,杜鲁涛. 基于外周血单个核细胞ATM基因甲基化的联合模型在胰腺癌早期诊断中的价值[J]. 山东大学学报 (医学版), 2025, 63(6): 78-88.
[5] 黄馨,王梦雪,付书璠,张琦悦,徐力. 代谢综合征及其组分与消化系统恶性肿瘤的因果关联:两样本孟德尔随机化研究[J]. 山东大学学报 (医学版), 2025, 63(5): 86-94.
[6] 王小磊,方骏,王安,朱武晖,史光军. 两样本孟德尔随机化分析肠道菌群与肝外胆管癌的因果关系[J]. 山东大学学报 (医学版), 2025, 63(4): 44-50.
[7] 李建锋,张展,丁新华,高奋堂,何勤利,谢萍. 欧洲人群饮食因素与认知功能障碍关系的孟德尔随机化分析[J]. 山东大学学报 (医学版), 2025, 63(4): 36-43.
[8] 徐晶晶,王新起,张洋,许旺旺,高进. P2X7受体抑制剂对青春期创伤后应激障碍大鼠行为及肠道菌群的影响[J]. 山东大学学报 (医学版), 2025, 63(4): 1-9.
[9] 杨慧,苏士晶,李芬. 基于双向孟德尔随机化法探讨组织蛋白酶与衰弱的因果关联[J]. 山东大学学报 (医学版), 2025, 63(2): 67-76.
[10] 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.
[11] 侯晓慧,Arezou Bikdeli,马超,李大庆. 250例NSTE-ACS患者ACE、KLK1及PTGIS基因型联合相关性分析[J]. 山东大学学报 (医学版), 2025, 63(2): 10-20.
[12] 杨慧敏,龚万里,侯雅琪,吴静,王洋,贺培凤,于琦. 20种氨基酸与冠心病的因果关联:孟德尔随机化研究[J]. 山东大学学报 (医学版), 2025, 63(12): 6-16.
[13] 杨春桃,左玉. MMP1、MMP9基因与慢性牙周炎的因果关系:基于两样本孟德尔随机化研究[J]. 山东大学学报 (医学版), 2025, 63(11): 87-97.
[14] 周坤,刘婷,姜艳菊,胡泽楷,李宇佳,冯武仪,黄继莉,叶汪泉,赵小峰,胡军. 孟德尔随机化分析膝骨关节炎疼痛与肌力的因果关联[J]. 山东大学学报 (医学版), 2025, 63(11): 61-67.
[15] 袁宗怀,潘广晔,迟曰梅,安传国,张永刚. 孟德尔随机化分析低级别浆液性卵巢癌与乳腺癌的因果关系[J]. 山东大学学报 (医学版), 2025, 63(1): 99-107.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
No Suggested Reading articles found!
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