title: The incidence rate over 10 years of naturally occurring, cancer related mutations in the basal core promoter of hepatitis B virus.
abstract: Cross-sectional analyses showed that the prevalence of basal core promoter (BCP) double mutations (nt 1762T, 1764A) of hepatitis B virus (HBV) gradually increases with age. We aimed to determine the incidence rate of the mutations over 10 years. Study subjects were selected from the Long An cohort established in 2004, including 59 with HBV with single mutations at nt 1762 or 1764 in the BCP and 342 with wild type BCP sequences at baseline. Their serum samples for analysis were obtained at the 3rd and 10th annual visits, respectively. The results showed that the annual incidence rate of BCP double mutations is 3.8% (95% confidence interval [CI]: 1.4-6.2) and tends to decrease with age. The peak incidence is in the 30-34 years age-group. The incidence rate in HBeAg positive individuals (5.5%) is significantly higher than in those without HBeAg (3.4%) (P<0.05). The incidence rate is significantly higher in genotype C (4.8%) than in genotype B (2.8%) or I (3.1%). The incidence rate of the mutations (6.8%) developing from a single mutation at nt 1762 or 1764 is significantly higher than that (3.8%) from the wild type sequence (P<0.005). The difference in incidence of single mutations between nt 1762 (0.7%) and 1764 (0.03%) is significant (P<0.05). In conclusion, the incidence rate of BCP double mutations tends to decrease with age after the age of 35 years. Viruses with a single mutation at nt 1762 or 1764 are more prone to develop double mutations. Nt 1762 is the more common site of the first mutation.
authors.affiliation: Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control, Guangxi Key Laboratory for the Prevention and Control of Viral Hepatitis, Nanning, Guangxi 530028, China.
authors.forename: Xue-Yan
authors.initials: XY
authors.lastname: Wang
authors.affiliation: Division of Medicine, UCL Medical School, London, UK.
authors.forename: Tim J
authors.initials: TJ
authors.lastname: Harrison
authors.affiliation: Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control, Guangxi Key Laboratory for the Prevention and Control of Viral Hepatitis, Nanning, Guangxi 530028, China.
authors.forename: Qin-Yan
authors.initials: QY
authors.lastname: Chen
authors.affiliation: Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control, Guangxi Key Laboratory for the Prevention and Control of Viral Hepatitis, Nanning, Guangxi 530028, China.
authors.forename: Hai
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Public Health of Guangxi Zhuang Autonomous Region, 35 TaoYuan Road, Nanning, Guangxi 530021, China.
authors.forename: Guo-Jian
authors.initials: GJ
authors.lastname: Li
authors.affiliation: Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control, Guangxi Key Laboratory for the Prevention and Control of Viral Hepatitis, Nanning, Guangxi 530028, China; School of Preclinical Medicine, Guangxi Medical University, 22 ShuangYong Road, Nanning, Guangxi 530021, China.
authors.forename: Mo-Han
authors.initials: MH
authors.lastname: Liu
authors.affiliation: Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control, Guangxi Key Laboratory for the Prevention and Control of Viral Hepatitis, Nanning, Guangxi 530028, China; School of Preclinical Medicine, Guangxi Medical University, 22 ShuangYong Road, Nanning, Guangxi 530021, China.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Hu
authors.affiliation: Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control, Guangxi Key Laboratory for the Prevention and Control of Viral Hepatitis, Nanning, Guangxi 530028, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Tan
authors.affiliation: Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control, Guangxi Key Laboratory for the Prevention and Control of Viral Hepatitis, Nanning, Guangxi 530028, China.
authors.forename: Qing-Li
authors.initials: QL
authors.lastname: Yang
authors.affiliation: Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control, Guangxi Key Laboratory for the Prevention and Control of Viral Hepatitis, Nanning, Guangxi 530028, China. Electronic address: zhongliaofang@hotmail.com.
authors.forename: Zhong-Liao
authors.initials: ZL
authors.lastname: Fang
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology / Q000821:virology*; D003430:Cross-Sectional Studies; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000235:genetics*; D006515:Hepatitis B virus / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000150:complications / Q000453:epidemiology / Q000821:virology*; D006801:Humans; D015994:Incidence; D008113:Liver Neoplasms / Q000453:epidemiology / Q000821:virology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D019562:Viral Load
chemical_list: D006514:Hepatitis B Surface Antigens
keywords: Basal core promoter; Genotypes; Hepatitis B virus; Incidence; Mutations