{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T11:36:18Z","timestamp":1764761778651,"version":"3.46.0"},"reference-count":169,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T00:00:00Z","timestamp":1764720000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Esophageal cancer (EC) is one of the most aggressive cancers of the digestive system, with two main subtypes: esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). Over four decades, the frequencies of EAC and Barrett\u2019s esophagus (BE), the known precursor lesion for EAC, have sharply increased in North America and Europe. This is mainly due to lifestyle and risk factors such as gastroesophageal reflux disease (GERD), obesity, and smoking. BE development to EAC involves numerous molecular modifications, including genetic and epigenetic alterations. Epigenetic changes, such as aberrant DNA methylation, play a critical role in the pathogenesis and progression of BE. This review discusses how non-genetic risk factors contribute to DNA methylation changes driving the transformation from BE to EAC, providing insights into the potential of developing methylation-based biomarkers for early diagnosis, risk stratification, and therapeutic intervention.<\/jats:p>","DOI":"10.3390\/ijms262311704","type":"journal-article","created":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T11:29:30Z","timestamp":1764761370000},"page":"11704","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Associations Between Non-Genetic Risk Factors and DNA Methylation Alterations in Barrett\u2019s Esophagus and Its Progression to Esophageal Adenocarcinoma"],"prefix":"10.3390","volume":"26","author":[{"given":"Nastaran","family":"Riahi Dehkordi","sequence":"first","affiliation":[{"name":"Faculty of Medicine and Health Sciences, University of Antwerp, 2000 Antwerpen, Belgium"},{"name":"Research and Development, Universal Diagnostics d.o.o., 1000 Ljubljana, Slovenia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristi","family":"Kruusmaa","sequence":"additional","affiliation":[{"name":"Research and Development, Universal Diagnostics d.o.o., 1000 Ljubljana, Slovenia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kausilia K.","family":"Krishnadath","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Medicine and Paediatrics, Department of Gastroenterology and Hepatology, University of Antwerp, University Hospital Antwerp, 2000 Antwerpen, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6088-7318","authenticated-orcid":false,"given":"Arianna","family":"Bertossi","sequence":"additional","affiliation":[{"name":"Research and Development, Universal Diagnostics d.o.o., 1000 Ljubljana, Slovenia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,3]]},"reference":[{"key":"ref_1","unstructured":"International Agency for Research on Cancer (IARC) (2024, January 16). 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