Department of Radiation Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
Guangxi Tumor Radiation Therapy Clinical Medical Research Center, Nanning, Guangxi, China.
Medicine (Baltimore). 2024 Mar 15;103(11):e37433. doi: 10.1097/MD.0000000000037433.
Patients with gastroesophageal reflux disease (GERD) are more likely to develop esophageal cancer (EC). However, a causal relationship between the 2 has been difficult to determine. Therefore, this study aimed to evaluate the impact of GERD on EC using the Mendelian randomization (MR) method. The causal association between GERD and EC was analyzed based on 2 publicly available genetic summary datasets for the GERD cohort (129,080 cases vs 473,524 controls) and the EC cohort (740 cases vs 372,016 controls). The causal inference was mainly evaluated by the inverse variance weighted MR. The MR-Egger regression, MR Pleiotropy Residual Sum and Outlier test, and leave-one-out test were used to confirm the sensitivity of the MR results. Possible interfering factors were excluded by multivariate MR (MVMR) analysis. We used 73 single nucleotide polymorphisms as instrumental variables. GERD was associated with increasing EC risk (odds ratio [OR], 1.001; 95% confidence interval, 1.001-1.002; P < .001), which was identified using the inverse variance weighted method. The sensitivity analysis also demonstrated similar results with the causal explanation, and major bias in genetic pleiotropy was not identified (intercept, 0.001; standard error, 0.001; P = .418). The multivariate MR analysis demonstrated the effect of GERD on EC even after excluding possible mediating factors (OR, 1.003; 95% confidence interval, 1.001-1.005; P = .012). This study confirmed that GERD has a causal effect on EC. Therefore, interventional measures are recommended to prevent EC.
胃食管反流病（GERD）患者更易患食管癌（EC）。然而，两者之间的因果关系很难确定。因此，本研究旨在使用孟德尔随机化（MR）方法评估 GERD 对 EC 的影响。基于 GERD 队列（129080 例病例与 473524 例对照）和 EC 队列（740 例病例与 372016 例对照）的 2 个公开可用的遗传汇总数据集，分析 GERD 与 EC 之间的因果关系。通过逆方差加权 MR 主要评估因果关系。MR-Egger 回归、MR 多效性残差总和和异常值检验以及逐一排除检验用于确认 MR 结果的敏感性。通过多变量 MR（MVMR）分析排除可能的干扰因素。我们使用 73 个单核苷酸多态性作为工具变量。GERD 与 EC 风险增加相关（优势比[OR]，1.001；95%置信区间，1.001-1.002；P<0.001），这是通过逆方差加权法确定的。敏感性分析也得出了与因果解释相似的结果，且未发现遗传多效性的主要偏倚（截距，0.001；标准误差，0.001；P=0.418）。即使在排除可能的中介因素后，MVMR 分析也表明 GERD 对 EC 的影响（OR，1.003；95%置信区间，1.001-1.005；P=0.012）。本研究证实 GERD 对 EC 有因果关系。因此，建议采取干预措施预防 EC。
