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Article: Genome-wide association study of hepatocellular carcinoma in Southern Chinese patients with chronic hepatitis B virus infection

TitleGenome-wide association study of hepatocellular carcinoma in Southern Chinese patients with chronic hepatitis B virus infection
Authors
KeywordsChromosome 8p
Data mining
Genetic association
Hepatitis b
Liver carcinogenesis
Issue Date2011
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
Citation
Plos One, 2011, v. 6 n. 12 How to Cite?
AbstractOne of the most relevant risk factors for hepatocellular carcinoma (HCC) development is chronic hepatitis B virus (HBV) infection, but only a fraction of chronic HBV carriers develop HCC, indicating that complex interactions among viral, environmental and genetic factors lead to HCC in HBV-infected patients. So far, host genetic factors have incompletely been characterized. Therefore, we performed a genome-wide association (GWA) study in a Southern Chinese cohort consisting of 95 HBV-infected HCC patients (cases) and 97 HBV-infected patients without HCC (controls) using the Illumina Human610-Quad BeadChips. The top single nucleotide polymorphisms (SNPs) were then validated in an independent cohort of 500 cases and 728 controls. 4 SNPs (rs12682266, rs7821974, rs2275959, rs1573266) at chromosome 8p12 showed consistent association in both the GWA and replication phases (OR combined = 1.31-1.39; p combined = 2.71×10 -5-5.19×10 -4; PAR combined = 26-31%). We found a 2.3-kb expressed sequence tag (EST) in the region using in-silico data mining and verified the existence of the full-length EST experimentally. The expression level of the EST was significantly reduced in human HCC tumors in comparison to the corresponding non-tumorous liver tissues (P<0.001). Results from sequence analysis and in-vitro protein translation study suggest that the transcript might function as a long non-coding RNA. In summary, our study suggests that variations at chromosome 8p12 may promote HCC in patients with HBV. Further functional studies of this region may help understand HBV-associated hepatocarcinogenesis. © 2011 Chan et al.
Persistent Identifierhttp://hdl.handle.net/10722/144557
ISSN
2023 Impact Factor: 2.9
2023 SCImago Journal Rankings: 0.839
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
Hong Kong Research Grants CouncilHKU 1/06C
HKU 7/CRG/09
Funding Information:

The study was supported by Hong Kong Research Grants Council Collaborative Research Fund (HKU 1/06C and HKU 7/CRG/09). I.O.L. Ng is Loke Yew Professor in Pathology. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

References
Grants

 

DC FieldValueLanguage
dc.contributor.authorChan, KYKen_HK
dc.contributor.authorWong, CMen_HK
dc.contributor.authorKwan, JSHen_HK
dc.contributor.authorLee, JMFen_HK
dc.contributor.authorCheung, KWen_HK
dc.contributor.authorYuen, MFen_HK
dc.contributor.authorLai, CLen_HK
dc.contributor.authorPoon, RTPen_HK
dc.contributor.authorSham, PCen_HK
dc.contributor.authorNg, IOLen_HK
dc.date.accessioned2012-02-03T06:13:41Z-
dc.date.available2012-02-03T06:13:41Z-
dc.date.issued2011en_HK
dc.identifier.citationPlos One, 2011, v. 6 n. 12en_HK
dc.identifier.issn1932-6203en_HK
dc.identifier.urihttp://hdl.handle.net/10722/144557-
dc.description.abstractOne of the most relevant risk factors for hepatocellular carcinoma (HCC) development is chronic hepatitis B virus (HBV) infection, but only a fraction of chronic HBV carriers develop HCC, indicating that complex interactions among viral, environmental and genetic factors lead to HCC in HBV-infected patients. So far, host genetic factors have incompletely been characterized. Therefore, we performed a genome-wide association (GWA) study in a Southern Chinese cohort consisting of 95 HBV-infected HCC patients (cases) and 97 HBV-infected patients without HCC (controls) using the Illumina Human610-Quad BeadChips. The top single nucleotide polymorphisms (SNPs) were then validated in an independent cohort of 500 cases and 728 controls. 4 SNPs (rs12682266, rs7821974, rs2275959, rs1573266) at chromosome 8p12 showed consistent association in both the GWA and replication phases (OR combined = 1.31-1.39; p combined = 2.71×10 -5-5.19×10 -4; PAR combined = 26-31%). We found a 2.3-kb expressed sequence tag (EST) in the region using in-silico data mining and verified the existence of the full-length EST experimentally. The expression level of the EST was significantly reduced in human HCC tumors in comparison to the corresponding non-tumorous liver tissues (P<0.001). Results from sequence analysis and in-vitro protein translation study suggest that the transcript might function as a long non-coding RNA. In summary, our study suggests that variations at chromosome 8p12 may promote HCC in patients with HBV. Further functional studies of this region may help understand HBV-associated hepatocarcinogenesis. © 2011 Chan et al.en_HK
dc.languageengen_US
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.actionen_HK
dc.relation.ispartofPLoS ONEen_HK
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectChromosome 8p-
dc.subjectData mining-
dc.subjectGenetic association-
dc.subjectHepatitis b-
dc.subjectLiver carcinogenesis-
dc.titleGenome-wide association study of hepatocellular carcinoma in Southern Chinese patients with chronic hepatitis B virus infectionen_HK
dc.typeArticleen_HK
dc.identifier.emailWong, CM: jcmwong@hkucc.hku.hken_HK
dc.identifier.emailYuen, MF: mfyuen@hku.hken_HK
dc.identifier.emailLai, CL: hrmelcl@hku.hken_HK
dc.identifier.emailPoon, RTP: poontp@hku.hken_HK
dc.identifier.emailSham, PC: pcsham@hku.hken_HK
dc.identifier.emailNg, IOL: iolng@hku.hken_HK
dc.identifier.authorityWong, CM=rp00231en_HK
dc.identifier.authorityYuen, MF=rp00479en_HK
dc.identifier.authorityLai, CL=rp00314en_HK
dc.identifier.authorityPoon, RTP=rp00446en_HK
dc.identifier.authoritySham, PC=rp00459en_HK
dc.identifier.authorityNg, IOL=rp00335en_HK
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1371/journal.pone.0028798en_HK
dc.identifier.pmid22174901-
dc.identifier.pmcidPMC3234276-
dc.identifier.scopuseid_2-s2.0-82955188800en_HK
dc.identifier.hkuros198351en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-82955188800&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume6en_HK
dc.identifier.issue12en_HK
dc.identifier.isiWOS:000298163600044-
dc.publisher.placeUnited Statesen_HK
dc.relation.projectMolecular pathology of liver cancer - a multidisciplinary study-
dc.identifier.scopusauthoridChan, KYK=36989360800en_HK
dc.identifier.scopusauthoridWong, CM=16314668400en_HK
dc.identifier.scopusauthoridKwan, JSH=37063349600en_HK
dc.identifier.scopusauthoridLee, JMF=54789830800en_HK
dc.identifier.scopusauthoridCheung, KW=54392710800en_HK
dc.identifier.scopusauthoridYuen, MF=7102031955en_HK
dc.identifier.scopusauthoridLai, CL=7403086396en_HK
dc.identifier.scopusauthoridPoon, RTP=7103097223en_HK
dc.identifier.scopusauthoridSham, PC=34573429300en_HK
dc.identifier.scopusauthoridNg, IOL=7102753722en_HK
dc.identifier.issnl1932-6203-

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