title: Potential Susceptibility Mutations in C Gene for Hepatitis B-Related Hepatocellular Carcinoma Identified by a Two-Stage Study in Qidong, China.
abstract: A two stage study was conducted to explore new potential mutations in the full genome of hepatitis B virus (HBV) on the progression of hepatocellular carcinoma (HCC) in Qidong, China. In stage 1, full genomes of HBV were compared between 30 HCC cases and 30 controls. In stage 2, an independent case-control study including 100 HCC cases and 100 controls was enrolled to verify the relationship between hot-spot mutations and HCC development. Furthermore, a longitudinal study was conducted on 11 HCC cases with serial serum samples available before HCC diagnosis. A total of 10 mutations (including pre-S2 start codon mutation and pre-Sdeletion in pre-Sgene, G1613A, C1653T, A1762T, and G1764A mutations inXgene, A2159G, A2189Y, G2203W, and C2288R mutations inCgene) showed an increased risk of HCC. In the validation study, pre-Sdeletion, C1653T, A1762T/G1764A, A2159G, A2189Y, G2203W, and C2288R mutations were associated with increased HCC risk in univariate analysis. Multivariate analysis indicated that pre-Sdeletion, A1762T/G1764A, A2159G, and A2189Y mutations were independently related with HCC development. Moreover, a significant biological gradient of HCC risk by number of mutations in theCgene was observed. Longitudinal observation demonstrated a gradual combination of the above mutations accumulated during the progression of HCC.
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong 226001, China. qulishuai1121@163.com.
authors.forename: Lishuai
authors.initials: L
authors.lastname: Qu
authors.affiliation: Department of Infectious Disease, Affiliated Hospital of Nantong University, Nantong 226001, China. firend20942@163.com.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong 226001, China. liujinxia850213@163.com.
authors.forename: Jinxia
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai 200032, China. liutaotao3@yeah.net.
authors.forename: Taotao
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai 200032, China. shenxizhong@126.com.
authors.forename: Xizhong
authors.initials: X
authors.lastname: Shen
authors.affiliation: Qidong Liver Cancer Institute, Qidong 226200, China. chentaoyang2@yeah.net.
authors.forename: Taoyang
authors.initials: T
authors.lastname: Chen
authors.affiliation: Qidong Liver Cancer Institute, Qidong 226200, China. nizhengpin@yeah.net.
authors.forename: Zhengpin
authors.initials: Z
authors.lastname: Ni
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong 226001, China. lucuihua@yeah.net.
authors.forename: Cuihua
authors.initials: C
authors.lastname: Lu
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000821:virology*; D002681:China; D005814:Genes, Viral / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D016679:Genome, Viral; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000821:virology*; D008137:Longitudinal Studies; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation
keywords: C gene; hepatitis B virus; hepatocellular carcinoma; mutation