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Article: High risk Epstein‐Barr virus variants characterized by distinct polymorphisms in the EBER locus are strongly associated with nasopharyngeal carcinoma

TitleHigh risk Epstein‐Barr virus variants characterized by distinct polymorphisms in the EBER locus are strongly associated with nasopharyngeal carcinoma
Authors
KeywordsEpstein–Barr virus
nasopharyngeal carcinoma
genome‐wide analysis
sequencing
EBV‐encoded small RNA
Issue Date2019
PublisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/journal/29331/home
Citation
International Journal of Cancer, 2019, v. 144 n. 12, p. 3031-3042 How to Cite?
AbstractWhether certain variants of Epstein–Barr virus (EBV) are linked to the pathogenesis of nasopharyngeal carcinoma (NPC), which shows a marked geographic restriction, remains an unresolved issue. We performed a case–control study comparing genomic sequences of EBV isolated from saliva samples of 142 population carriers with those from primary tumour biopsies derived from 62 patients with NPC of Hong Kong. Cluster analysis discovered five EBV subgroups 1A‐C and 2A‐B amongst the population carriers in contrast to the predominance of 1A and ‐B in the majority of NPC. Genome‐wide association study (GWAS) identified a panel of NPC‐associated single nucleotide polymorphisms (SNPs) and indels in the EBER locus. The most significant polymorphism, which can be found in 96.8% NPC cases and 40.1% population carriers of Hong Kong, is a four‐base‐deletion polymorphism downstream of EBER2 (EBER‐del) from coordinates 7188–7191 (p = 1.91 × 10−7). In addition, the predicted secondary structure of EBER2 is altered with likely functional consequence in nearly all NPC cases. Using the SNPs and indels associated with NPC, genetic risk score is assigned for each EBV variant. EBV variants with high genetic risk score are found to be much more prevalent in Hong Kong Chinese than individuals of other geographic regions and in NPC than other EBV‐associated cancers. We conclude that high risk EBV variants with polymorphisms in the EBER locus, designated as HKNPC‐EBERvar, are strongly associated with NPC. Further investigation of the biological function and potential clinical application of these newly identified polymorphisms in NPC and other EBV‐associated cancers is warranted.
Persistent Identifierhttp://hdl.handle.net/10722/279035
ISSN
2017 Impact Factor: 7.36
2015 SCImago Journal Rankings: 2.657

 

DC FieldValueLanguage
dc.contributor.authorHui, KF-
dc.contributor.authorChan, TF-
dc.contributor.authorYang, W-
dc.contributor.authorShen, JJ-
dc.contributor.authorLam, KP-
dc.contributor.authorKwok, H-
dc.contributor.authorSham, PC-
dc.contributor.authorTsao, SW-
dc.contributor.authorKwong, DL-
dc.contributor.authorLung, ML-
dc.contributor.authorChiang, AKS-
dc.date.accessioned2019-10-21T02:18:26Z-
dc.date.available2019-10-21T02:18:26Z-
dc.date.issued2019-
dc.identifier.citationInternational Journal of Cancer, 2019, v. 144 n. 12, p. 3031-3042-
dc.identifier.issn0020-7136-
dc.identifier.urihttp://hdl.handle.net/10722/279035-
dc.description.abstractWhether certain variants of Epstein–Barr virus (EBV) are linked to the pathogenesis of nasopharyngeal carcinoma (NPC), which shows a marked geographic restriction, remains an unresolved issue. We performed a case–control study comparing genomic sequences of EBV isolated from saliva samples of 142 population carriers with those from primary tumour biopsies derived from 62 patients with NPC of Hong Kong. Cluster analysis discovered five EBV subgroups 1A‐C and 2A‐B amongst the population carriers in contrast to the predominance of 1A and ‐B in the majority of NPC. Genome‐wide association study (GWAS) identified a panel of NPC‐associated single nucleotide polymorphisms (SNPs) and indels in the EBER locus. The most significant polymorphism, which can be found in 96.8% NPC cases and 40.1% population carriers of Hong Kong, is a four‐base‐deletion polymorphism downstream of EBER2 (EBER‐del) from coordinates 7188–7191 (p = 1.91 × 10−7). In addition, the predicted secondary structure of EBER2 is altered with likely functional consequence in nearly all NPC cases. Using the SNPs and indels associated with NPC, genetic risk score is assigned for each EBV variant. EBV variants with high genetic risk score are found to be much more prevalent in Hong Kong Chinese than individuals of other geographic regions and in NPC than other EBV‐associated cancers. We conclude that high risk EBV variants with polymorphisms in the EBER locus, designated as HKNPC‐EBERvar, are strongly associated with NPC. Further investigation of the biological function and potential clinical application of these newly identified polymorphisms in NPC and other EBV‐associated cancers is warranted.-
dc.languageeng-
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/journal/29331/home-
dc.relation.ispartofInternational Journal of Cancer-
dc.rightsThis is the peer reviewed version of the following article: International Journal of Cancer, 2019, v. 144 n. 12, p. 3031-3042, which has been published in final form at https://doi.org/10.1002/ijc.32049. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.-
dc.subjectEpstein–Barr virus-
dc.subjectnasopharyngeal carcinoma-
dc.subjectgenome‐wide analysis-
dc.subjectsequencing-
dc.subjectEBV‐encoded small RNA-
dc.titleHigh risk Epstein‐Barr virus variants characterized by distinct polymorphisms in the EBER locus are strongly associated with nasopharyngeal carcinoma-
dc.typeArticle-
dc.identifier.emailHui, KF: kfhui@hku.hk-
dc.identifier.emailYang, W: yangwl@hku.hk-
dc.identifier.emailTsao, SW: gswtsao@hku.hk-
dc.identifier.emailKwong, DL: dlwkwong@hku.hk-
dc.identifier.emailLung, ML: mlilung@hku.hk-
dc.identifier.emailChiang, AKS: chiangak@hku.hk-
dc.identifier.authorityYang, W=rp00524-
dc.identifier.authorityTsao, SW=rp00399-
dc.identifier.authorityKwong, DL=rp00414-
dc.identifier.authorityLung, ML=rp00300-
dc.identifier.authorityChiang, AKS=rp00403-
dc.description.naturepostprint-
dc.identifier.doi10.1002/ijc.32049-
dc.identifier.pmid30536939-
dc.identifier.scopuseid_2-s2.0-85059573834-
dc.identifier.hkuros308115-
dc.identifier.volume144-
dc.identifier.issue12-
dc.identifier.spage3031-
dc.identifier.epage3042-
dc.publisher.placeUnited States-

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