{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T23:03:05Z","timestamp":1767999785842,"version":"3.49.0"},"reference-count":25,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2011,12,27]],"date-time":"2011-12-27T00:00:00Z","timestamp":1324944000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[2013,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The WW domain\u2010containing oxidoreductase (WWOX) gene, located on chromosome 16q23.3\u201324.1 in the region recognized as the common fragile site FRA16D is considered to be a tumor suppressor gene involved in various carcinomas. The present study was to investigate the alterations of WWOX expression and its correlation with polymorphism, the level of WWOX loss of heterozygosity (LOH), and methylation status in esophageal squamous cell carcinoma (ESCC). Immunohistochemistry and RT\u2010PCR methods were used, respectively, to examine the protein and mRNA expression of WWOX in ESCC tissues. PCR\u2010RFLP, PCR\u2010SSLP, and MSP approach were used, respectively, to detect polymorphisms of rs3764340, rs2548861, and rs1079635 site, the level of LOH, and WWOX methylation status. Family history of upper gastrointestinal cancer (UGIC) significantly increased the risk of developing ESCC. Protein and mRNA expression of WWOX was reduced in ESCC tumor tissues and was associated with LOH and hypermethylation of the gene. The G allele of rs3764340 significantly elevated the risk of developing ESCC and was associated with TNM stage. LOH at the WWOX loci was observed in 41.4% tumors. The hypermethylation of promoter and exon1 of WWOX was found to be occurred in dysplastic tissues and the methylation frequency of WWOX in ESCC tumor tissues <jats:styled-content>was<\/jats:styled-content> significantly higher than that in corresponding normal tissues and was associated with UGIC family history. In all, these results indicate that the WWOX gene may play an important role in the development of ESCC especially in individuals with UGIC family history. \u00a9 2011 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/mc.21853","type":"journal-article","created":{"date-parts":[[2011,12,27]],"date-time":"2011-12-27T13:50:22Z","timestamp":1324993822000},"page":"265-274","source":"Crossref","is-referenced-by-count":16,"title":["Decreased expression of WWOX in the development of esophageal squamous cell carcinoma"],"prefix":"10.1002","volume":"52","author":[{"given":"Wei","family":"Guo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guiying","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuran","family":"Dong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanli","family":"Guo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gang","family":"Kuang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiming","family":"Dong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2011,12,27]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijsu.2010.06.011"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00432-007-0283-0"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v12.i43.6933"},{"key":"e_1_2_7_5_2","first-page":"2140","article-title":"WWOX, a novel WW domain\u2010containing protein mapping to human chromosome 16q23.3\u201024.1, a region frequently affected in breast cancer","volume":"60","author":"Bednarek AK","year":"2000","journal-title":"Cancer Res"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.5507\/bp.2007.002"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0400805101"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-1150"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.191175898"},{"key":"e_1_2_7_10_2","first-page":"47","article-title":"WWOX, the tumour suppressor gene affected in multiple cancers","volume":"60","author":"Lewandowska U","year":"2009","journal-title":"J Physiol Pharmacol"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1208398"},{"key":"e_1_2_7_12_2","first-page":"2258","article-title":"Genetic alterations of the tumor suppressor gene WWOX in esophageal squamous cell 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