| 贺非凡,顾建华,李佳悦,等.吸烟、代谢标志物和多级别胃黏膜病变及胃癌风险的关联：基于河南林州上消化道肿瘤筛查队列的横断面研究[J].中国肿瘤,2024,33(3):240-246. |
| 吸烟、代谢标志物和多级别胃黏膜病变及胃癌风险的关联：基于河南林州上消化道肿瘤筛查队列的横断面研究 |
| Association of Smoking Status， Metabolic Markers， and Risk of Multigrade Gastric Mucosal Lesions and Gastric Cancer： A Cross-Sectional Study Based on Upper Gastrointestinal Cancer Screeing Program in Linzhou， Henan |
| 投稿时间：2023-07-03 |
| DOI：10.11735/j.issn.1004-0242.2024.03.A011 |
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| 中文关键词: 胃癌 胃黏膜病变 吸烟 代谢组学 |
| 英文关键词:gastric cancer gastric mucosal lesions smoking metabolomics |
| 基金项目:北京市科技新星计划（Z201100006820069）；中国医学科学院医学与健康科技创新工程（2021-I2M-1-023）；中国医学科学院医学与健康科技创新工程（2021-I2M-1-010） |
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| 中文摘要: |
| 摘 要：［目的］ 探讨人群吸烟状况、代谢标志物和多级别胃黏膜病变及胃癌风险的关联。［方法］ 选取2007—2012年间河南林州上消化道肿瘤筛查队列中经病理诊断为肠上皮化生（39例）、高级别上皮内瘤变及胃癌（44例）以及健康者（56名）共139名为研究对象，使用超高效液相色谱-高分辨率质谱法对基线血样的代谢物进行定量检测。采用线性回归分析吸烟状况与代谢标志物之间的关系，并进一步采用Logistic回归分析代谢标志物与多级别胃黏膜病变及胃癌风险间的关系。筛选潜在代谢标志物，构建随机森林模型，评价其对多级别胃黏膜病变及胃癌风险诊断能力。［结果］ 在1 270种代谢物中发现58种代谢物与吸烟状况相关，其中4种代谢物同时与多级别胃黏膜病变及胃癌风险相关。4-甲基邻苯二酚-1-硫酸盐（效应值=2.82，95%CI：1.91~3.73，P<0.01；OR=1.41，95%CI：1.05~1.89，P<0.05）、4-乙酰基苯酚硫酸盐（效应值=3.08，95%CI：2.08~4.08，P<0.01；OR=1.35，95%CI：1.05~1.72，P<0.05）以及羟基可替宁（效应值=6.20，95%CI：5.19~7.21，P<0.01；OR=1.42，95%CI：1.07~1.88，P<0.05）与吸烟状况呈正相关的同时，增加胃黏膜病变及胃癌风险。乳糖神经酰胺（效应值=-0.28，95%CI：-0.51~-0.06，P<0.05；OR=0.21，95%CI：0.07~0.69，P<0.01）与吸烟状况呈现负相关的同时，降低胃黏膜病变及胃癌风险。整合这4种代谢物显著提升了预测多级别胃黏膜病变及胃癌进展的能力（AUC=0.714，95%CI：0.629~0.801）。［结论］ 在研究人群中发现4种代谢标志物同时与吸烟状况和多级别胃黏膜病变及胃癌风险存在关联，这可能部分解释了吸烟对胃癌的风险作用，同时可能作为识别高危人群和发现早期胃癌的生物标志物，具有潜在应用价值。 |
| 英文摘要: |
| Abstract：［Purpose］ To investigate the associations among smoking， metabolic markers and risk of multigrade gastric mucosal lesions and gastric cancer. ［Methods］ A total of 139 individuals who participated in the upper gastrointestinal cancer screening in Linzhou of Henan ?妆rovince from 2007 to 2012 were enrolled in the study， including 39 cases of pathologically confirmed intestinal metaplasia (IM)， 44 cases of high-grade intraepithelial neoplasia (HGIN) or gastric cancer and 56 normal subjects. Liquid chromatography-mass spectrometry was used to quantify the metabolites in plasma samples. Linear regression was conducted to assess associations between smoking status and metabolic markers， and Logistic regression was applied to further analyze the association be ween these metabolic markers and the risk of multigrade gastric mucosal lesions and gastric cancer. The efficiency of plasma metabolic markers in predicting the risk of multigrade gastric mucosal lesions and gastric cancer was evaluated by a random forest model. ［Results］ Smoking status was associated with 58 out of 1 270 plasma markers， 4 of which were associated with multigrade gastric mucosal lesions and gastric cancer risk. The 4-methylcatechol-1-sulfate(coefficient=2.82， 95%CI： 1.91， 3.73， P<0.01； OR=1.41， 95%CI： 1.05~1.89， P<0.05)， 4-acetylphenol sulfate(coefficient=3.08， 95%CI： 2.08， 4.08， P<0.01； OR=1.35， 95%CI： 1.05~1.72， P<0.05)， and hydroxycotinine (coefficient=6.20， 95%CI： 5.19~ 7.21， P<0.01； OR=1.42， 95%CI： 1.07~1.88， P<0.05) were positively associated with smoking status and increasing the risk of multigrade gastric mucosal lesions and gastric cancer； while CerG2 (d34：2)-LacCer (d18：2/16：0)(coefficient=-0.28， 95%CI： -0.51~-0.06， P<0.05； OR=0.21， 95%CI： 0.07~0.69， P<0.01) was negatively associated with smoking status and decreasing the risk of multigrade gastric mucosal lesions and gastric cancer. Integration of these four metabolites significantly improved the performance for predicting the progression of multigrade gastric mucosal lesions and the risk of gastric cancer (AUC=0.714， 95%CI： 0.629~0.801). ［Conclusion］ The study shows that 4 plasma metabolic markers are associated with both smoking status and multigrade gastric mucosal lesions and gastric cancer risk， which may partially explain the risk effect of smoking on gastric cancer， and may have potential application as biomarkers for assessing high-risk populations and early diagnosis of gastric cancer. |
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