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

One 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...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Kelvin Yuen-Kwong Chan, Chun-Ming Wong, Johnny Sheung-Him Kwan, Joyce Man-Fong Lee, Ka Wai Cheung, Man Fung Yuen, Ching Lung Lai, Ronnie Tung-Ping Poon, Pak Chung Sham, Irene Oi-Lin Ng
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/812c9fb17746415cab7039183dc6c517
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:812c9fb17746415cab7039183dc6c517
record_format	dspace
spelling	oai:doaj.org-article:812c9fb17746415cab7039183dc6c5172021-11-18T07:32:42ZGenome-wide association study of hepatocellular carcinoma in Southern Chinese patients with chronic hepatitis B virus infection.1932-620310.1371/journal.pone.0028798https://doaj.org/article/812c9fb17746415cab7039183dc6c5172011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22174901/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203One 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.Kelvin Yuen-Kwong ChanChun-Ming WongJohnny Sheung-Him KwanJoyce Man-Fong LeeKa Wai CheungMan Fung YuenChing Lung LaiRonnie Tung-Ping PoonPak Chung ShamIrene Oi-Lin NgPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 12, p e28798 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kelvin Yuen-Kwong Chan Chun-Ming Wong Johnny Sheung-Him Kwan Joyce Man-Fong Lee Ka Wai Cheung Man Fung Yuen Ching Lung Lai Ronnie Tung-Ping Poon Pak Chung Sham Irene Oi-Lin Ng Genome-wide association study of hepatocellular carcinoma in Southern Chinese patients with chronic hepatitis B virus infection.
description	One 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.
format	article
author	Kelvin Yuen-Kwong Chan Chun-Ming Wong Johnny Sheung-Him Kwan Joyce Man-Fong Lee Ka Wai Cheung Man Fung Yuen Ching Lung Lai Ronnie Tung-Ping Poon Pak Chung Sham Irene Oi-Lin Ng
author_facet	Kelvin Yuen-Kwong Chan Chun-Ming Wong Johnny Sheung-Him Kwan Joyce Man-Fong Lee Ka Wai Cheung Man Fung Yuen Ching Lung Lai Ronnie Tung-Ping Poon Pak Chung Sham Irene Oi-Lin Ng
author_sort	Kelvin Yuen-Kwong Chan
title	Genome-wide association study of hepatocellular carcinoma in Southern Chinese patients with chronic hepatitis B virus infection.
title_short	Genome-wide association study of hepatocellular carcinoma in Southern Chinese patients with chronic hepatitis B virus infection.
title_full	Genome-wide association study of hepatocellular carcinoma in Southern Chinese patients with chronic hepatitis B virus infection.
title_fullStr	Genome-wide association study of hepatocellular carcinoma in Southern Chinese patients with chronic hepatitis B virus infection.
title_full_unstemmed	Genome-wide association study of hepatocellular carcinoma in Southern Chinese patients with chronic hepatitis B virus infection.
title_sort	genome-wide association study of hepatocellular carcinoma in southern chinese patients with chronic hepatitis b virus infection.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/812c9fb17746415cab7039183dc6c517
work_keys_str_mv	AT kelvinyuenkwongchan genomewideassociationstudyofhepatocellularcarcinomainsouthernchinesepatientswithchronichepatitisbvirusinfection AT chunmingwong genomewideassociationstudyofhepatocellularcarcinomainsouthernchinesepatientswithchronichepatitisbvirusinfection AT johnnysheunghimkwan genomewideassociationstudyofhepatocellularcarcinomainsouthernchinesepatientswithchronichepatitisbvirusinfection AT joycemanfonglee genomewideassociationstudyofhepatocellularcarcinomainsouthernchinesepatientswithchronichepatitisbvirusinfection AT kawaicheung genomewideassociationstudyofhepatocellularcarcinomainsouthernchinesepatientswithchronichepatitisbvirusinfection AT manfungyuen genomewideassociationstudyofhepatocellularcarcinomainsouthernchinesepatientswithchronichepatitisbvirusinfection AT chinglunglai genomewideassociationstudyofhepatocellularcarcinomainsouthernchinesepatientswithchronichepatitisbvirusinfection AT ronnietungpingpoon genomewideassociationstudyofhepatocellularcarcinomainsouthernchinesepatientswithchronichepatitisbvirusinfection AT pakchungsham genomewideassociationstudyofhepatocellularcarcinomainsouthernchinesepatientswithchronichepatitisbvirusinfection AT ireneoilinng genomewideassociationstudyofhepatocellularcarcinomainsouthernchinesepatientswithchronichepatitisbvirusinfection
_version_	1718423297486487552

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

Ejemplares similares