Liu Yu-Xin, Bin Cheng-Li, Zhang Lu, Yang Wen-Tao, An Bai-Ping
Department of Oncology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, Sichuan Province, China.
Department of Gynecology and Obstetrics, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, Sichuan Province, China.
World J Gastrointest Oncol. 2024 Jun 15;16(6):2631-2645. doi: 10.4251/wjgo.v16.i6.2631.
Previous observational studies have shown that the prevalence of gastroesophageal reflux disease (GERD) and Barrett's esophagus (BE) is associated with socioeconomic status. However, due to the methodological limitations of traditional observational studies, it is challenging to definitively establish causality.
To explore the causal relationship between the prevalence of these conditions and socioeconomic status using Mendelian randomization (MR).
We initially screened single nucleotide polymorphisms (SNPs) to serve as proxies for eight socioeconomic status phenotypes for univariate MR analysis. The inverse variance weighted (IVW) method was used as the primary analytical method to estimate the causal relationship between the eight socioeconomic status phenotypes and the risk of GERD and BE. We then collected combinations of SNPs as composite proxies for the eight socioeconomic phenotypes to perform multivariate MR (MVMR) analyses based on the IVW MVMR model. Furthermore, a two-step MR mediation analysis was used to examine the potential mediation of the associations by body mass index, major depressive disorder (MDD), smoking, alcohol consumption, and sleep duration.
The study identified three socioeconomic statuses that had a significant impact on GERD. These included household income [odds ratio (OR): 0.46; 95% confidence interval (95%CI): 0.31-0.70], education attainment (OR: 0.23; 95%CI: 0.18-0.29), and the Townsend Deprivation Index at recruitment (OR: 1.57; 95%CI: 1.04-2.37). These factors were found to independently and predominantly influence the genetic causal effect of GERD. Furthermore, the mediating effect of educational attainment on GERD was found to be mediated by MDD (proportion mediated: 10.83%). Similarly, the effect of educational attainment on BE was mediated by MDD (proportion mediated: 10.58%) and the number of cigarettes smoked per day (proportion mediated: 3.50%). Additionally, the mediating effect of household income on GERD was observed to be mediated by sleep duration (proportion mediated: 9.75%).
This MR study shed light on the link between socioeconomic status and GERD or BE, providing insights for the prevention of esophageal cancer and precancerous lesions.
既往观察性研究表明，胃食管反流病（GERD）和巴雷特食管（BE）的患病率与社会经济地位相关。然而，由于传统观察性研究的方法学局限性，明确因果关系具有挑战性。
采用孟德尔随机化（MR）方法探讨这些疾病的患病率与社会经济地位之间的因果关系。
我们最初筛选单核苷酸多态性（SNP）作为8种社会经济地位表型的代理变量，用于单变量MR分析。采用逆方差加权（IVW）法作为主要分析方法，以估计8种社会经济地位表型与GERD和BE风险之间的因果关系。然后，我们收集SNP组合作为8种社会经济表型的复合代理变量，基于IVW MVMR模型进行多变量MR（MVMR）分析。此外，采用两步MR中介分析来检验体重指数、重度抑郁症（MDD）、吸烟、饮酒和睡眠时间对这些关联的潜在中介作用。
该研究确定了三种对GERD有显著影响的社会经济地位。这些包括家庭收入[比值比（OR）：0.46；95%置信区间（95%CI）：0.31 - 0.70]、教育程度（OR：0.23；95%CI：0.18 - 0.29）以及招募时的汤森贫困指数（OR：1.57；95%CI：1.04 - 2.37）。发现这些因素独立且主要影响GERD的遗传因果效应。此外，发现教育程度对GERD的中介作用由MDD介导（中介比例：10.83%）。同样，教育程度对BE的影响由MDD介导（中介比例：10.58%）和每日吸烟量介导（中介比例：3.50%）。此外，观察到家庭收入对GERD的中介作用由睡眠时间介导（中介比例：9.75%）。
这项MR研究揭示了社会经济地位与GERD或BE之间的联系，为食管癌和癌前病变的预防提供了见解。
