{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T08:22:07Z","timestamp":1781079727425,"version":"3.54.1"},"reference-count":53,"publisher":"BMJ","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gut"],"published-print":{"date-parts":[[2009,1]]},"abstract":"<jats:sec>\n                  <jats:title>Background:<\/jats:title>\n                  <jats:p>The accumulation of reactive oxygen species and subsequent oxidative DNA damage underlie the development of Barrett\u2019s oesophagus (BO) and its progression to Barrett\u2019s dysplasia (BD) and adenocarcinoma (BAC).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods:<\/jats:title>\n                  <jats:p>The promoter regions of 23 genes of the glutathione <jats:italic>S<\/jats:italic>-transferase (GST) and glutathione peroxidase (GPX) families were systematically analysed. Quantitative bisulfite pyrosequencing, real-time RT-PCR, western blot and immunohistochemical (IHC) analysis methods were utilised in this study.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results:<\/jats:title>\n                  <jats:p>14 genes were identified that have CpG islands around their transcription start sites: GSTs (<jats:italic>GSTM2\u2013M5<\/jats:italic>, <jats:italic>GSTA4<\/jats:italic>, <jats:italic>GSTP1<\/jats:italic>, <jats:italic>GSTZ1<\/jats:italic>, <jats:italic>GSTT2<\/jats:italic>, <jats:italic>GSTO1<\/jats:italic> and <jats:italic>GSTO2<\/jats:italic>) and GPXs (<jats:italic>GPX1<\/jats:italic>, <jats:italic>GPX3<\/jats:italic>, <jats:italic>GPX4<\/jats:italic> and <jats:italic>GPX7<\/jats:italic>). Analysis of an initial set of 20 primary samples demonstrated promoter DNA hypermethylation and mRNA downregulation of <jats:italic>GPX3<\/jats:italic>, <jats:italic>GPX7<\/jats:italic>, <jats:italic>GSTM2<\/jats:italic>, <jats:italic>GSTM3<\/jats:italic> and <jats:italic>GSTM5<\/jats:italic> in more than half of the BAC samples. Further analysis of 159 primary human samples (37 normal, 11 BO, 11 BD and 100 BACs) indicated frequent hypermethylation (\u2a7e10% methylation) of <jats:italic>GPX3<\/jats:italic> (62%), <jats:italic>GPX7<\/jats:italic> (67%), <jats:italic>GSTM2<\/jats:italic> (69.1%) and <jats:italic>GSTM3<\/jats:italic> (15%) in BACs. A significant inverse correlation between DNA methylation and mRNA expression level was shown for <jats:italic>GPX3<\/jats:italic> (p&lt;0.001), <jats:italic>GPX7<\/jats:italic> (p\u200a=\u200a0.002), <jats:italic>GSTM2<\/jats:italic> (p&lt;0.001) and <jats:italic>GSTM5<\/jats:italic> (p\u200a=\u200a0.01). Treatment of oesophageal cancer cell lines with 5-aza-2\u2032-deoxycytidine and trichostatin-A led to reversal of the methylation pattern and re-expression of these genes at the mRNA and protein levels. The IHC analysis of GPX3, GPX7 and GSTM2 on a tissue microarray that contained 75 BACs with normal squamous oesophageal samples demonstrated an absent to weak staining in tumours (52% for GPX3, 57% for GPX7 and 45% for GSTM2) and a moderate to strong immunostaining in normal samples.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion:<\/jats:title>\n                  <jats:p>Epigenetic inactivation of members of the glutathione pathway can be an important mechanism in Barrett\u2019s tumourigenesis.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/gut.2007.146290","type":"journal-article","created":{"date-parts":[[2008,7,29]],"date-time":"2008-07-29T22:50:16Z","timestamp":1217371816000},"page":"5-15","source":"Crossref","is-referenced-by-count":144,"title":["DNA hypermethylation regulates the expression of members of the Mu-class glutathione <i>S<\/i>-transferases and glutathione peroxidases in Barrett\u2019s adenocarcinoma"],"prefix":"10.1136","volume":"58","author":[{"given":"D F","family":"Peng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Razvi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Washington","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Roessner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Schneider-Stock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W","family":"El-Rifai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2008,7,29]]},"reference":[{"key":"2025090722440071000_58.1.5.1","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1002\/ssu.2980060509","article-title":"Adenocarcinoma in Barrett\u2019s esophagus.","volume":"6","author":"Altorki","year":"1990","journal-title":"Semin Surg Oncol"},{"key":"2025090722440071000_58.1.5.2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19890715)64:2<526::AID-CNCR2820640228>3.0.CO;2-B"},{"key":"2025090722440071000_58.1.5.3","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1993.03510110056031"},{"key":"2025090722440071000_58.1.5.4","doi-asserted-by":"publisher","DOI":"10.1097\/00001574-200407000-00013"},{"key":"2025090722440071000_58.1.5.5","doi-asserted-by":"publisher","DOI":"10.1055\/s-2001-11669"},{"key":"2025090722440071000_58.1.5.6","first-page":"3410","article-title":"Epigenetic patterns in the progression of esophageal adenocarcinoma.","volume":"61","author":"Eads","year":"2001","journal-title":"Cancer Res"},{"key":"2025090722440071000_58.1.5.7","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2001.27215"},{"key":"2025090722440071000_58.1.5.8","first-page":"200","article-title":"Molecular biology of esophageal cancer.","volume":"27","author":"Metzger","year":"2004","journal-title":"Onkologie"},{"key":"2025090722440071000_58.1.5.9","doi-asserted-by":"publisher","DOI":"10.1016\/S0027-5107(01)00091-4"},{"key":"2025090722440071000_58.1.5.10","doi-asserted-by":"publisher","DOI":"10.1007\/s001090050031"},{"key":"2025090722440071000_58.1.5.11","doi-asserted-by":"publisher","DOI":"10.2741\/1667"},{"key":"2025090722440071000_58.1.5.12","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/S0027-5107(01)00199-3","article-title":"Involvement of oxidative stress in experimentally induced reflux esophagitis and Barrett\u2019s esophagus: clue for the chemoprevention of esophageal carcinoma by antioxidants.","volume":"480\u2013481","author":"Lee","year":"2001","journal-title":"Mutat Res"},{"key":"2025090722440071000_58.1.5.13","doi-asserted-by":"publisher","DOI":"10.1136\/gut.37.2.168"},{"key":"2025090722440071000_58.1.5.14","doi-asserted-by":"crossref","unstructured":"Wetscher GJ Hinder RA Klingler P .Reflux esophagitis in humans is a free radical event. 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