title: Association of novel mutations and haplotypes in the preS region of hepatitis B virus with hepatocellular carcinoma.
abstract: The association of viral mutations and haplotypic carriages with mutations in the preS region of hepatitis B virus (HBV) genotypes B and C with hepatocellular carcinoma (HCC) is of great significance for the prediction of this malignancy, but it remains obscure. We analyzed the preS sequences of HBV genotypes B and C from 1172 HBV-infected subjects including 231 patients with HCC. As compared with the HBV-infected subjects without HCC, C2875T, G2946C, A3054C, C3060A, T3066C, C3116T, A3120C, G3191A, A1C, C7A, C10A, A31C, C76T, G105C, and G147C in both genotypes were significantly associated with increased risks of HCC. C2875A, G2950A, G2951A, A3054T, C3060T, T3066A, T3069G, A3120T, and G3191C were significantly associated with increased risks of HCC in genotype C, whereas these mutations were inversely associated with HCC in genotype B. Multivariate regression analyses showed that C76A/T was a novel factor independently associated with an increased risk of HCC, as compared with those without HCC. The frequencies of haplotypes 2964A-3116T-preS2 start codon wild-type-7C, 2964C-3116T-7A-76C, and 2964A-3116T-7C-76A/T were significantly higher in the patients with HCC (P<0.001), whereas a haplotypic carriage with a single mutation and another three wildtypes were inversely associated with HCC. Conclusively, the association of HBV mutations in the preS region with HCC depends on HBV genotype and haplotypic carriage with two or more mutations that are each associated with an increased risk of HCC independently.
authors.affiliation: Department of Epidemiology, Second Military Medical University, Shanghai, 200433, China.
authors.forename: Jia-Xin
authors.initials: JX
authors.lastname: Xie
authors.forename: Jun
authors.initials: J
authors.lastname: Zhao
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Yin
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.forename: Rui
authors.initials: R
authors.lastname: Pu
authors.forename: Wen-Ying
authors.initials: WY
authors.lastname: Lu
authors.forename: Hong-Wei
authors.initials: HW
authors.lastname: Zhang
authors.forename: Hong-Yang
authors.initials: HY
authors.lastname: Wang
authors.forename: Guang-Wen
authors.initials: GW
authors.lastname: Cao
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000453:epidemiology / Q000821:virology*; D005838:Genotype; D006239:Haplotypes; D006514:Hepatitis B Surface Antigens / Q000235:genetics; D006515:Hepatitis B virus / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000503:physiopathology / Q000821:virology; D006801:Humans; D008113:Liver Neoplasms / Q000453:epidemiology / Q000821:virology*; D008969:Molecular Sequence Data; D015999:Multivariate Analysis; D009154:Mutation; D011498:Protein Precursors / Q000235:genetics; D012307:Risk Factors; D014759:Viral Envelope Proteins / Q000235:genetics*
chemical_list: D006514:Hepatitis B Surface Antigens; D011498:Protein Precursors; C118669:S envelope protein, hepatitis B virus; D014759:Viral Envelope Proteins; C050806:presurface protein 1, hepatitis B surface antigen; C050807:presurface protein 2, hepatitis B surface antigen