{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T07:47:32Z","timestamp":1769240852138,"version":"3.49.0"},"reference-count":32,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2012,11,30]],"date-time":"2012-11-30T00:00:00Z","timestamp":1354233600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Environ and Mol Mutagen"],"published-print":{"date-parts":[[2013,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>WWOX<\/jats:italic> is a tumor suppressor gene that maps to the common fragile site FRA16D and is involved in carcinogenesis and cancer progression in many different carcinomas. Reduced WWOX expression is associated with more aggressive phenotypes and poor patient outcomes in several cancers. The present study was conducted in order to elucidate more precisely the genetic and epigenetic alterations of <jats:italic>WWOX<\/jats:italic> that play a role in gastric cardia adenocarcinoma (GCA) carcinogenesis in a population from Northern China. Polymerase chain reaction\u2010restriction fragment length polymorphism (PCR\u2010RFLP), PCR\u2010simple sequence length polymorphism (PCR\u2010SSLP), and methylation specific PCR (MSP) methods were used to characterize polymorphisms in the rs3764340, rs2548861, and rs1079635 loci, the level of loss of heterozygosity (LOH), and methylation status of <jats:italic>WWOX<\/jats:italic>, respectively. Protein and mRNA expression of WWOX in GCA tissues was quantified by immunohistochemistry and reverse transcription\u2010PCR (RT\u2010PCR). Family history of upper gastrointestinal cancer (UGIC) significantly increased the risk of developing GCA. The CG+GG genotype of rs3764340 and GT or TT genotype of rs2548861 significantly elevated the risk of developing GCA. LOH at the <jats:italic>WWOX<\/jats:italic> locus was observed in 45.6% tumors. The promoter and exon 1 methylation frequency of <jats:italic>WWOX<\/jats:italic> in GCA tissues <jats:styled-content>was<\/jats:styled-content> significantly higher than in corresponding normal tissues and was associated with UGIC family history. Protein and mRNA expression of <jats:italic>WWOX<\/jats:italic> was reduced in GCA tumor tissues and was associated with LOH and methylation of the gene. These results indicate that <jats:italic>WWOX<\/jats:italic> may play an important role in GCA especially in individuals with UGIC family history. Environ. Mol. Mutagen., 2013. \u00a9  2012 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/em.21748","type":"journal-article","created":{"date-parts":[[2012,11,30]],"date-time":"2012-11-30T13:12:37Z","timestamp":1354281157000},"page":"112-123","source":"Crossref","is-referenced-by-count":12,"title":["Genetic and epigenetic alterations of <i>WWOX<\/i> in the development of gastric cardia adenocarcinoma"],"prefix":"10.1002","volume":"54","author":[{"given":"Wei","family":"Guo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiming","family":"Dong","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":"Zhibin","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,11,30]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0400805101"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-1150"},{"key":"e_1_2_7_4_1","first-page":"2140","article-title":"WWOX, a novel WW domain\u2010containing protein mapping to human chromosome 16q23.3\u201324.1, a region frequently affected in breast cancer","volume":"60","author":"Bednarek AK","year":"2000","journal-title":"Cancer Res"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1066726"},{"key":"e_1_2_7_6_1","first-page":"903","article-title":"Overexpression of the steroid receptor coactivator AIB1 in breast cancer correlates with the absence of estrogen and progesterone receptors and positivity for p53 and HER2\/neu","volume":"61","author":"Bouras T","year":"2001","journal-title":"Cancer Res"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.25937"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCG.0b013e3180f6262c"},{"key":"e_1_2_7_9_1","first-page":"3225","article-title":"A gene hypermethylation profile of human cancer","volume":"61","author":"Esteller M","year":"2001","journal-title":"Cancer Res"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1080\/07357900802620828"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.271.5247.350"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.5507\/bp.2007.002"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M806688200"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1208398"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-06-2038"},{"key":"e_1_2_7_16_1","first-page":"940","article-title":"Expression of FRA16D\/WWOX and FRA3B\/FHIT genes in hematopoietic malignancies","volume":"1","author":"Ishii H","year":"2003","journal-title":"Mol Cancer Res"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-010-0254-1"},{"key":"e_1_2_7_18_1","first-page":"2258","article-title":"Genetic alterations of the tumor suppressor gene WWOX in esophageal squamous cell carcinoma","volume":"62","author":"Kuroki T","year":"2002","journal-title":"Cancer Res"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-03-0096"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.20891"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2008.07.002"},{"issue":"1","key":"e_1_2_7_22_1","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_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-010-0956-y"},{"key":"e_1_2_7_24_1","first-page":"1683","article-title":"Chromosomal fragile site FRA16D and DNA instability in cancer","volume":"60","author":"Mangelsdorf M","year":"2000","journal-title":"Cancer Res"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/16.3.1215"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.2008.00841.x"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6604986"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.191175898"},{"key":"e_1_2_7_29_1","first-page":"pii","article-title":"DNA extraction from paraffin embedded material for genetic and epigenetic analyses","volume":"26","author":"Pikor LA","year":"2011","journal-title":"J Vis Exp"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.20616"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1159\/000197911"},{"key":"e_1_2_7_32_1","first-page":"878","article-title":"WW domain containing oxidoreductase gene expression is altered in non\u2010small cell lung cancer","volume":"63","author":"Yendamuri S","year":"2003","journal-title":"Cancer Res"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13277-010-0150-5"}],"container-title":["Environmental and Molecular Mutagenesis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fem.21748","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/em.21748","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,22]],"date-time":"2023-11-22T02:16:24Z","timestamp":1700619384000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/em.21748"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,11,30]]},"references-count":32,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2013,3]]}},"alternative-id":["10.1002\/em.21748"],"URL":"https:\/\/doi.org\/10.1002\/em.21748","archive":["Portico"],"relation":{},"ISSN":["0893-6692","1098-2280"],"issn-type":[{"value":"0893-6692","type":"print"},{"value":"1098-2280","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,11,30]]}}}