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Article: Epigenetic alterations of a novel antioxidant gene SLC22A3 predispose susceptible individuals to increased risk of esophageal cancer.

TitleEpigenetic alterations of a novel antioxidant gene SLC22A3 predispose susceptible individuals to increased risk of esophageal cancer.
Authors
KeywordsFamilial ESCC
SLC22A3
DNA methylation
antioxidant gene
oxidative DNA damage
Issue Date2018
PublisherIvyspring International Publisher. The Journal's web site is located at http://www.biolsci.org/index.htm
Citation
International Journal of Biological Sciences, 2018, v. 14 n. 12, p. 1658-1668 How to Cite?
AbstractEsophageal squamous cell carcinoma (ESCC) occurs with the highest frequency in China, especially in the high-risk Northern Chinese. Recent studies have reported that SLC22A3 is significantly downregulated in non-tumor (NT) esophageal tissues from familial ESCC patients compared with those from sporadic ESCC. However, the mechanism of how SLC22A3 regulates familial ESCC remains unknown. In this study, post hoc genome-wide association studies (GWAS) in 496 cases with a family history of upper gastrointestinal tract cancers and 1056 controls were performed and the results revealed that SLC22A3 is a novel susceptibility gene for familial ESCC. Reduced expression of SLC22A3 in NT esophageal tissues from familial ESCC patients significantly correlates with its promoter hypermethylation. Moreover, case-control study of Chinese descendants from different risk areas of China revealed that the methylation of the SLC22A3 gene in peripheral blood leukocyte (PBL) DNA samples could be a risk factor for developing ESCC in this high-risk population. Functional studies showed that SLC22A3 is a novel antioxidant gene, and deregulation of SLC22A3 facilitates heat stress-induced oxidative DNA damage and formation of gamma-H2AX foci in normal esophageal epithelial cells. Collectively, we show that epigenetic alterations of SLC22A3 predispose susceptible individuals to increased risk of esophageal cancer.
Persistent Identifierhttp://hdl.handle.net/10722/274902
ISSN
2017 Impact Factor: 4.057
2015 SCImago Journal Rankings: 1.927
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorXiong, JX-
dc.contributor.authorWang, YS-
dc.contributor.authorSheng, J-
dc.contributor.authorXiang, D-
dc.contributor.authorHuang, TX-
dc.contributor.authorTan, BB-
dc.contributor.authorZeng, CM-
dc.contributor.authorLi, HH-
dc.contributor.authorYang, J-
dc.contributor.authorMeltzer, SJ-
dc.contributor.authorMori, Y-
dc.contributor.authorQin, YR-
dc.contributor.authorGuan, X-
dc.contributor.authorFu, L-
dc.date.accessioned2019-09-10T02:31:15Z-
dc.date.available2019-09-10T02:31:15Z-
dc.date.issued2018-
dc.identifier.citationInternational Journal of Biological Sciences, 2018, v. 14 n. 12, p. 1658-1668-
dc.identifier.issn1449-2288-
dc.identifier.urihttp://hdl.handle.net/10722/274902-
dc.description.abstractEsophageal squamous cell carcinoma (ESCC) occurs with the highest frequency in China, especially in the high-risk Northern Chinese. Recent studies have reported that SLC22A3 is significantly downregulated in non-tumor (NT) esophageal tissues from familial ESCC patients compared with those from sporadic ESCC. However, the mechanism of how SLC22A3 regulates familial ESCC remains unknown. In this study, post hoc genome-wide association studies (GWAS) in 496 cases with a family history of upper gastrointestinal tract cancers and 1056 controls were performed and the results revealed that SLC22A3 is a novel susceptibility gene for familial ESCC. Reduced expression of SLC22A3 in NT esophageal tissues from familial ESCC patients significantly correlates with its promoter hypermethylation. Moreover, case-control study of Chinese descendants from different risk areas of China revealed that the methylation of the SLC22A3 gene in peripheral blood leukocyte (PBL) DNA samples could be a risk factor for developing ESCC in this high-risk population. Functional studies showed that SLC22A3 is a novel antioxidant gene, and deregulation of SLC22A3 facilitates heat stress-induced oxidative DNA damage and formation of gamma-H2AX foci in normal esophageal epithelial cells. Collectively, we show that epigenetic alterations of SLC22A3 predispose susceptible individuals to increased risk of esophageal cancer.-
dc.languageeng-
dc.publisherIvyspring International Publisher. The Journal's web site is located at http://www.biolsci.org/index.htm-
dc.relation.ispartofInternational Journal of Biological Sciences-
dc.rightsInternational Journal of Biological Sciences. Copyright © Ivyspring International Publisher.-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectFamilial ESCC-
dc.subjectSLC22A3-
dc.subjectDNA methylation-
dc.subjectantioxidant gene-
dc.subjectoxidative DNA damage-
dc.titleEpigenetic alterations of a novel antioxidant gene SLC22A3 predispose susceptible individuals to increased risk of esophageal cancer.-
dc.typeArticle-
dc.identifier.emailGuan, X: xyguan@hku.hk-
dc.identifier.authorityGuan, X=rp00454-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.7150/ijbs.28482-
dc.identifier.pmid30416380-
dc.identifier.scopuseid_2-s2.0-85056310095-
dc.identifier.hkuros302587-
dc.identifier.volume14-
dc.identifier.issue12-
dc.identifier.spage1658-
dc.identifier.epage1668-
dc.identifier.isiWOS:000447937900006-
dc.publisher.placeAustralia-

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