食管癌相关风险因素的孟德尔随机化研究-现代医学

食管癌相关风险因素的孟德尔随机化研究

单位：1. 新疆医科大学公共卫生学院, 新疆乌鲁木齐 830011;
2. 新疆医科大学附属肿瘤医院内镜诊疗中心, 新疆乌鲁木齐 830011;
3. 新疆医科大学附属肿瘤医院肿瘤防治办公室, 新疆乌鲁木齐 830011;
4. 新疆医科大学护理学院, 新疆乌鲁木齐 830011

关键词：食管癌风险因素孟德尔随机化孟德尔随机化-贝叶斯模型平均法

分类号：R735.1

出版年·卷·期（页码）：2025·53·第二期（187-196）

摘要：

目的：基于孟德尔随机化方法探讨个体特征、饮食摄入及疾病相关等方面风险因素与食管癌之间的因果关系，为食管癌的早期预防提供依据。方法：基于全基因组关联分析(Genome-wide association study，GWAS)获得与31个暴露因素相关的遗传变异数据，通过两样本孟德尔随机化方法及贝叶斯平均的多元孟德尔随机化方法(MR-BMA)，分析与食管癌的因果风险因素，通过留一法、异质性检验、水平多效性检验、Q统计量和Cook距离验证结果的稳定性和可靠性。结果：单元孟德尔随机化分析结果显示BMI (OR=1.000 9，95%CI:1.000 2~1.001 5)、吸烟(OR=1.007 9，95%CI:1.003 1~1.012 8)、胃食管反流病(OR=1.001 3，95%CI:1.000 5~1.002 1)及甲亢(OR=1.033 8,95%CI:1.007 1~1.061 2)会增加食管癌患病的风险，而受教育时间(OR=0.998 6，95%CI:0.997 6~0.999 6)及运动习惯(OR=0.990 2，95%CI:0.981 5~0.998 9)会降低食管癌患病风险，并且以上影响因素多效性检验结果显示不存在水平多效性。MR-BMA结果显示BMI (MIP=0.545)是因果证据最强的暴露因素，经验P=0.017，具有统计学意义，其它暴露因素的均无统计学意义。结论： BMI、吸烟、胃食管反流病及甲亢为食管癌的危险因素。受教育时间及运动习惯可能为食管癌的保护因素。其中BMI是一个独立的暴露因素，可能对其他暴露因素存在介导作用。

Objective: To explore the causal relationship between individual characteristics, dietary intake and disease-related risk factors and esophageal cancer based on Mendelian randomization, and to provide a basis for the early prevention of esophageal cancer. Methods: Based on Genome-wide association study(GWAS) to obtain genetic variant data associated with 31 exposure factors, the causal risk factors associated with esophageal cancer were analyzed by the unit two-sample Mendelian randomization method and the multivariate Mendelian randomization method with Bayesian averaging(MR-BMA) by leave-one-out method, heterogeneity test, horizontal multivariate test, Q statistic and Cook distance to verify the stability and reliability of the results. Result:The results of unitary Mendelian randomization analysis showed that BMI(OR=1.000 9, 95%CI:1.000 2~1.001 5), smoking(OR=1.007 9, 95%CI:1.003 1~1.012 8), gastroesophageal reflux disease(OR=1.001 3, 95%CI:1.000 5~1.002 1) and hyperthyroidism(OR=1.033 8, 95%CI:1.007 1~1.061 2) increased the risk of esophageal cancer, whereas the duration of education(OR=0.998 6, 95%CI:0.997 6~0.999 6) and physical activity habits(OR=0.990 2, 95%CI:0.981 5~0.998 9) decreased the risk of esophageal cancer. The results of multivariate test of the above influences showed no horizontal multivariate. the MR-BMA results showed that BMI(MIP=0.545) was the exposure factor with the strongest evidence of causality, with an empirical P=0.017, which was statistically significant, and no statistically significant results were found for any other exposure factors. Conclusion: BMI, smoking, GERD and hyperthyroidism may be risk factors for esophageal cancer. Level of education and exercise habits may be protective factors for esophageal cancer. Among them, BMI is an independent exposure factor and may have a mediating effect on other exposure factors.

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