---
title: "Epigenetic Alterations in Barrett's Esophagus and Esophageal Cancer: DNA Methylation and Clinical"
id: "pubmed-42671081"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42671081"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42671081/"
doi: "10.1002/gcc.70167"
published_at: "2026-09-01T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Epigenetic Alterations in Barrett's Esophagus and Esophageal Cancer: DNA Methylation and Clinical
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42671081
- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42671081/)
- **DOI:** [10.1002/gcc.70167](https://doi.org/10.1002%2Fgcc.70167)
- **Published At:** 2026-09-01T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- Esophageal cancer (OC) remains a major global cancer with poor 5-year survival (~10%–20%), and **Barrett's Esophagus** (BO) is the principal risk factor for esophageal adenocarcinoma (OAC). - The molecular pathogenesis of BO and OC is incompletely understood; recent work highlights epigenetic dysregulation as a key area of interest. - **DNA methylation** is the most extensively studied epigenetic mechanism in this context and is implicated in initiation and progression of both OAC and esophageal squamous cell carcinoma (OSCC). - Aberrant methylation events affect genes involved in critical pathways including **Wnt signaling** and cell cycle control, which may contribute to carcinogenesis. - Epigenetically regulated genes show promise as diagnostic, prognostic, and risk-stratification **biomarkers** for BO populations, but translation to clinical use faces challenges. - The review synthesizes current findings, highlights caveats in existing studies, and outlines future research directions needed to improve understanding of OC pathogenesis and patient outcomes. - Keywords emphasized in the source include Barrett's esophagus, DNA methylation, epigenetics, and esophageal cancer. - The source is a 2026 review in Genes, Chromosomes and Cancer (PMID 42671081; DOI 10.1002/gcc.70167) authored by Louise Lawless et al., affiliated with Technological University Dublin.
## Clinical Analysis & Structured Key Points
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Affiliations Expand ### Affiliations * 1 Sustainability and Health Research Hub, Greenway Hub, Technological University Dublin, Dublin, Ireland. * 2 School of Biological, Health and Sports Sciences, Technological University Dublin, Dublin, Ireland. * 3 Research Ireland Centre for Research Training in Machine Learning, Technological University Dublin, Dublin, Ireland. * PMID: **42671081** * DOI: [ 10.1002/gcc.70167 ](https://doi.org/10.1002/gcc.70167) Item in Clipboard Review # Understanding the Epigenetic Landscape of Barrett's Esophagus and Esophageal Cancer: A Review of Current Findings, Caveats and Future Directions Louise Lawless et al. Genes Chromosomes Cancer. 2026 Sep. Show details Display options Display options Format Abstract PubMed PMID Genes Chromosomes Cancer Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Genes+Chromosomes+Cancer%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Genes+Chromosomes+Cancer%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42671081/) . 2026 Sep;65(9):e70167. doi: 10.1002/gcc.70167. ### Authors [Louise Lawless](https://pubmed.ncbi.nlm.nih.gov/?term=Lawless+L&cauthor_id=42671081)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42671081/#short-view-affiliation-1 "Sustainability and Health Research Hub, Greenway Hub, Technological University Dublin, Dublin, Ireland.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42671081/#short-view-affiliation-2 "School of Biological, Health and Sports Sciences, Technological University Dublin, Dublin, Ireland."), [Trevor Doherty](https://pubmed.ncbi.nlm.nih.gov/?term=Doherty+T&cauthor_id=42671081)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42671081/#short-view-affiliation-2 "School of Biological, Health and Sports Sciences, Technological University Dublin, Dublin, Ireland.")[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42671081/#short-view-affiliation-3 "Research Ireland Centre for Research Training in Machine Learning, Technological University Dublin, Dublin, Ireland."), [Carla Surlis](https://pubmed.ncbi.nlm.nih.gov/?term=Surlis+C&cauthor_id=42671081)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42671081/#short-view-affiliation-2 "School of Biological, Health and Sports Sciences, Technological University Dublin, Dublin, Ireland."), [Niamh Gilmartin](https://pubmed.ncbi.nlm.nih.gov/?term=Gilmartin+N&cauthor_id=42671081)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42671081/#short-view-affiliation-1 "Sustainability and Health Research Hub, Greenway Hub, Technological University Dublin, Dublin, Ireland.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42671081/#short-view-affiliation-2 "School of Biological, Health and Sports Sciences, Technological University Dublin, Dublin, Ireland."), [Therese M Murphy](https://pubmed.ncbi.nlm.nih.gov/?term=Murphy+TM&cauthor_id=42671081)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42671081/#short-view-affiliation-1 "Sustainability and Health Research Hub, Greenway Hub, Technological University Dublin, Dublin, Ireland.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42671081/#short-view-affiliation-2 "School of Biological, Health and Sports Sciences, Technological University Dublin, Dublin, Ireland.")[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42671081/#short-view-affiliation-3 "Research Ireland Centre for Research Training in Machine Learning, Technological University Dublin, Dublin, Ireland.") ### Affiliations * 1 Sustainability and Health Research Hub, Greenway Hub, Technological University Dublin, Dublin, Ireland. * 2 School of Biological, Health and Sports Sciences, Technological University Dublin, Dublin, Ireland. * 3 Research Ireland Centre for Research Training in Machine Learning, Technological University Dublin, Dublin, Ireland. * PMID: **42671081** * DOI: [ 10.1002/gcc.70167 ](https://doi.org/10.1002/gcc.70167) Item in Clipboard Cite Display options Display options Format Abstract PubMed PMID ## Abstract Esophageal 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 of Wnt 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. **Keywords:** Barrett's esophagus; DNA methylation; epigenetics; esophageal cancer. © 2026 The Author(s). Genes, Chromosomes and Cancer published by Wiley Periodicals LLC. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Similar articles * [ Role of epigenetic alterations in the pathogenesis of Barrett's esophagus and esophageal adenocarcinoma. ](https://pubmed.ncbi.nlm.nih.gov/22808291/) Agarwal A, Polineni R, Hussein Z, Vigoda I, Bhagat TD, Bhattacharyya S, Maitra A, Verma A.Agarwal A, et al.Int J Clin Exp Pathol. 2012;5(5):382-96. Epub 2012 May 23.Int J Clin Exp Pathol. 2012.PMID: 22808291Free PMC article.Review. * [ Aberrant methylation of secreted frizzled-related protein genes in esophageal adenocarcinoma and Barrett's esophagus. ](https://pubmed.ncbi.nlm.nih.gov/15825175/) Zou H, Molina JR, Harrington JJ, Osborn NK, Klatt KK, Romero Y, Burgart LJ, Ahlquist DA.Zou H, et al.Int J Cancer. 2005 Sep 10;116(4):584-91. doi: 10.1002/ijc.21045.Int J Cancer. 2005.PMID: 15825175 * [ Associations Between Non-Genetic Risk Factors and DNA Methylation Alterations in Barrett's Esophagus and Its Progression to Esophageal Adenocarcinoma. ](https://pubmed.ncbi.nlm.nih.gov/41373857/) Riahi Dehkordi N, Kruusmaa K, Krishnadath KK, Bertossi A.Riahi Dehkordi N, et al.Int J Mol Sci. 2025 Dec 3;26(23):11704. doi: 10.3390/ijms262311704.Int J Mol Sci. 2025.PMID: 41373857Free PMC article.Review. * [ Identification of Subtypes of Barrett's Esophagus and Esophageal Adenocarcinoma Based on DNA Methylation Profiles and Integration of Transcriptome and Genome Data. ](https://pubmed.ncbi.nlm.nih.gov/32032585/) Jammula S, Katz-Summercorn AC, Li X, Linossi C, Smyth E, Killcoyne S, Biasci D, Subash VV, Abbas S, Blasko A, Devonshire G, Grantham A, Wronowski F, O'Donovan M, Grehan N, Eldridge MD, Tavaré S; Oesophageal Cancer Clinical and Molecular Stratification (OCCAMS) consortium; Fitzgerald RC.Jammula S, et al.Gastroenterology. 2020 May;158(6):1682-1697.e1. doi: 10.1053/j.gastro.2020.01.044. Epub 2020 Feb 4.Gastroenterology. 2020.PMID: 32032585Free PMC article. * [ Epigenetic biomarkers in esophageal cancer. ](https://pubmed.ncbi.nlm.nih.gov/22406828/) Kaz AM, Grady WM.Kaz AM, et al.Cancer Lett. 2014 Jan 28;342(2):193-9. doi: 10.1016/j.canlet.2012.02.036. Epub 2012 Mar 7.Cancer Lett. 2014.PMID: 22406828Free PMC article.Review. [ See all similar articles ](https://pubmed.ncbi.nlm.nih.gov/?linkname=pubmed_pubmed&from_uid=42671081) ## References 1. 1. D. J. Uhlenhopp, E. O. Then, T. Sunkara, and V. Gaduputi, “Epidemiology of Esophageal Cancer: Update in Global Trends, Etiology and Risk Factors,” Clinical Journal of Gastroenterology 13 (2020): 1010–1021, [https://doi.org/10.1007/s12328‐020‐01237‐x](https://doi.org/10.1007/s12328%E2%80%90020%E2%80%9001237%E2%80%90x). 2. 1. F. L. Huang and S. J. Yu, “Esophageal Cancer: Risk Factors, Genetic Association, and Treatment,” Asian Journal of Surgery 41, no. 3 (2018): 210–215, . 3. 1. C. Q. Liu, Y. L. Ma, Q. Qin, et al., “Epidemiology of Esophageal Cancer in 2020 and Projections to 2030 and 2040,” Thoracic Cancer 14, no. 1 (2022): 3–11, [https://doi.org/10.1111/1759‐7714.14745](https://doi.org/10.1111/1759%E2%80%907714.14745). 4. 1. A. P. Thrift, “The Epidemic of Oesophageal Carcinoma: Where Are We Now?,” Cancer Epidemiology 41 (2016): 88–95, . 5. 1. E. O. Then, M. Lopez, S. Saleem, et al., “Esophageal Cancer: An Updated Surveillance Epidemiology and End Results Database Analysis,” World Journal of Oncology 11, no. 2 (2020): 55–64, . Show all 100 references ## Publication types * Review Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Review%22%5Bpt%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Review) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42671081/) ## MeSH terms * Adenocarcinoma* / genetics Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Adenocarcinoma%2Fgenetics%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Adenocarcinoma) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42671081/) * Adenocarcinoma* / pathology Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Adenocarcinoma%2Fpathology%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Adenocarcinoma) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42671081/) * Barrett Esophagus* / genetics Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Barrett+Esophagus%2Fgenetics%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Barrett+Esophagus) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42671081/) * Barrett Esophagus* / pathology Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Barrett+Esophagus%2Fpathology%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Barrett+Esophagus) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42671081/) * Biomarkers, Tumor / genetics Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Biomarkers%2C+Tumor%2Fgenetics%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Biomarkers%2C+Tumor) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42671081/) * DNA Methylation Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22DNA+Methylation%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=DNA+Methylation) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42671081/) * Epigenesis, Genetic* Ac
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