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The molecular mechanisms driving Barrett's Esophagus and cancer remain incompletely defined, prompting attention to epigenetic dysregulation, especially aberrant DNA methylation. This review synthesizes current knowledge on DNA methylation alterations in esophageal cancer initiation and progression, and evaluates their biomarker potential for early detection, prognosis, and risk stratification, including roles in Wnt signaling and cell-cycle control, and highlights future research directions and challenges.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/understanding-the-epigenetic-landscape-of-barretts-esophagus-and-esophageal-cancer-a-review-of-current-findings-caveats-and-future-directions/349604/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/understanding-the-epigenetic-landscape-of-barretts-esophagus-and-esophageal-cancer-a-review-of-current-findings-caveats-and-future-directions/349604.png","ImageObject",300,407,{"name":92,"@type":93},"anakgang17","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-27","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":14},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is the main epigenetic focus of this review?","Question",{"text":112,"@type":113},"The review centers on epigenetic dysregulation, particularly aberrant DNA methylation, as the most extensively researched epigenetic mechanism in esophageal cancer.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How is Barrett's Esophagus connected to esophageal adenocarcinoma in this document?",{"text":117,"@type":113},"Barrett's Esophagus is presented as the primary risk factor for developing esophageal adenocarcinoma, and the review emphasizes epigenetic changes originating in Barrett's Esophagus.",{"name":119,"@type":110,"acceptedAnswer":120},"What biomarker applications does the review discuss?",{"text":121,"@type":113},"It discusses DNA methylation-associated alterations and their potential clinical use as diagnostic, prognostic, and therapeutic biomarkers, including early detection and risk stratification in Barrett's Esophagus populations.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},349604,1790482076,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":14,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145},962090883568,"https://ap-avatar.wpscdn.com/davatar_a8503ba1806abce46bf441b54a3ca4cd","Genes, Chromosomes and Cancer  \nUnderstanding the Epigenetic Landscape of Barrett's Esophagus and Esophageal Cancer: A Review of Current Findings, Caveats and Future Directions  \nLouise Lawless1,2  | Trevor Doherty2,3 | Carla Surlis2 | Niamh Gilmartin1,2 | Therese M. Murphy1,2,3   \n1Sustainability and Health Research Hub, Greenway Hub, Technological University Dublin, Dublin, Ireland | 2School of Biological, Health and Sports Sciences, Technological University Dublin, Dublin, Ireland | 3Research Ireland Centre for Research Training in Machine Learning, Technological University Dublin, Dublin, Ireland  \nCorrespondence: Therese M. Murphy ([therese.murphy@tudublin.ie](therese.murphy@tudublin.ie))  \nReceived: 10 June 2026 | Revised: 12 August 2026 | Accepted: 20 August 2026  \nKeywords: Barrett's esophagus | DNA methylation | epigenetics | esophageal cancer  \nABSTRACT  \nEsophageal cancer (OC) is currently the eighth most common form of cancer worldwide with a 5-year survival rate of 10%–20%, with the primary risk factor of esophageal adenocarcinoma (OAC) being the development of Barrett's Esophagus (BO) . Despite its clinical significance, the molecular pathogenesis underlying both BO and OC is not well understood. In recent years, epigenetic dysregulation, particularly aberrant DNA methylation, has emerged as a critical area of investigation, given its potential utility in the identification of diagnostic, prognostic, and therapeutic biomarkers. This review examines the evolving epigenetic landscape of esophageal cancer, including a focus on its origins in BO with a particular emphasis on DNA methylation, the most extensively researched epigenetic mechanism. Key DNA methylation-associated alterations involved in OAC and OSCC initiation and progression are discussed, alongside their potential clinical application as biomarkers for early detection, prognosis, and risk stratification in BO populations. Furthermore, the role of these epigenetically regulated genes in the disruption ofWnt signaling and cell cycle control pathways implicated in esophageal carcinogenesis is explored. The review concludes by outlining future research directions, current challenges, and the promise of epigenetic studies in advancing our understanding of OC pathogenesis and improving patient outcomes.  \n1 | Introduction  \nEsophageal cancer (OC) is currently the eighth most common form of cancer worldwide [1] .  \nThe incidence rate is rapidly increasing, with a sixfold increase reported in recent years [2] . OC primarily includes two main subtypes: squamous cell carcinoma (OSCC) and adenocarcinoma (OAC), each with distinct molecular characteristics, risk factors, and clinical outcomes [3] . While OSCC is most common, OAC rates are rising in Western countries, predominantly  \nin Europe, the Americas, and Australia [1] . The causes for the rise in cases are generally unknown; however, it has been speculated that the upsurge could be due to increasing prevalence of risk factors such as obesity and heartburn [4] . All subtypes of OC have a high mortality rate and despite improvement in treatments, the 5-year survival rate remains 10%–20%[2, 5] . High mortality rates are mostly linked to the absence of early clinical symptoms and OC typically being detected in later stages when treatment options are reduced [3]. The primary risk factor for developing OAC is the presence of Barrett's Esophagus (BO) [6], a complication of gastroesophageal reflux disease (GERD) [3] . BO  \n\n| Niamh Gilmartin and Therese M. Murphy contributed equally to this study. |\n| --- |\n| This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.\u003Cbr>© 2026 The Author(s). Genes, Chromosomes and Cancer published by Wiley Periodicals LLC. |\n\nGenes, Chromosomes and Cancer, 2026; 65:e70167 1 of 15  \n[https://doi.org/10.1002/gcc.70167](https://doi.org/10.1002/gc","cbCaig5fFbWuHTzA","https://ap.wps.com/l/cbCaig5fFbWuHTzA","pdf",2087097,15,"English","# Introduction\n## Overview of esophageal cancer subtypes and Barrett's Esophagus risk\n# Methods\n## PICO framework and literature screening approach\n## PRISMA-based systematic review workflow","[{\"question\":\"What is the main epigenetic focus of this review?\",\"answer\":\"The review centers on epigenetic dysregulation, particularly aberrant DNA methylation, as the most extensively researched epigenetic mechanism in esophageal cancer.\"},{\"question\":\"How is Barrett's Esophagus connected to esophageal adenocarcinoma in this document?\",\"answer\":\"Barrett's Esophagus is presented as the primary risk factor for developing esophageal adenocarcinoma, and the review emphasizes epigenetic changes originating in Barrett's Esophagus.\"},{\"question\":\"What biomarker applications does the review discuss?\",\"answer\":\"It discusses DNA methylation-associated alterations and their potential clinical use as diagnostic, prognostic, and therapeutic biomarkers, including early detection and risk stratification in Barrett's Esophagus populations.\"}]","Understanding the Epigenetic Landscape of Barrett's Esophagus and Esophageal Cancer - A Review of Current Findings, Caveats and Future Directions | PDF",1790084473,38]