Clinical and Translational Research
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Jun 15, 2024; 16(6): 2631-2645
Published online Jun 15, 2024. doi: 10.4251/wjgo.v16.i6.2631
Socioeconomic traits and the risk of Barrett’s esophagus and gastroesophageal reflux disease: A Mendelian randomization study
Yu-Xin Liu, Cheng-Li Bin, Lu Zhang, Wen-Tao Yang, Bai-Ping An
Yu-Xin Liu, Bai-Ping An, Department of Oncology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, Sichuan Province, China
Cheng-Li Bin, Department of Gynecology and Obstetrics, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, Sichuan Province, China
Lu Zhang, Department of Endocrine, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, Sichuan Province, China
Wen-Tao Yang, Department of Cardiovascular, Chengdu Integrated TCM & Western Medicine Hospital, Chengdu 610041, Sichuan Province, China
Author contributions: Liu YX contributed to conceptualization, methodology, investigation, validation, writing of the original draft, visualization of the data, and software; Bin CL contributed to methodology, investigation, validation; Yang WT contributed to formal analysis of the data and provided supervision; An BP contributed to funding acquisition, and reviewing and editing of the manuscript for important intellectual content; Zhang L contributed to methodology, and investigation and validation of the data; all authors read and agreed to the published version of the manuscript.
Supported by Sichuan Research Center for Coordinated Development of TCM Culture, No. 2022XT12.
Conflict-of-interest statement: The authors declare that they have no conflicts of interest.
Data sharing statement: All the data used in this study are available at https://gwas.mrcieu.ac.uk (accessed on 9 October 2023).
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Bai-Ping An, Doctor, Attending Doctor, Department of Oncology, Hospital of Chengdu University of Traditional Chinese Medicine, No. 39 Shi-er-Qiao Road, Chengdu 610072, Sichuan Province, China. anbaiping@cdutcm.edu.cn
Received: January 9, 2024
Revised: February 5, 2024
Accepted: April 8, 2024
Published online: June 15, 2024
Processing time: 157 Days and 14.7 Hours
Abstract
BACKGROUND

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.

AIM

To explore the causal relationship between the prevalence of these conditions and socioeconomic status using Mendelian randomization (MR).

METHODS

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.

RESULTS

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%)

CONCLUSION

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.

Keywords: Socioeconomic status; Gastroesophageal reflux disease; Barrett’s esophagus; Two-step Mendelian randomization; Multivariate Mendelian randomization

Core Tip: This study linked the Townsend Deprivation Index at recruitment to a higher risk of gastroesophageal reflux disease (GERD), while household income and educational attainment protected against GERD. Additionally, our study provided a deeper understanding of the causal effects of educational attainment and household income on GERD and Barrett’s esophagus. Sleep, major depressive disorder, and smoking mediated the relationship between socioeconomic status and GERD or Barret’s esophagus. This Mendelian randomization study has significant public health implications for primary and secondary prevention of esophageal cancer.