title: Hepatitis B virus genotype, mutations, human leukocyte antigen polymorphisms and their interactions in hepatocellular carcinoma: a multi-centre case-control study.
abstract: Three genome-wide association studies (GWAS) have been conducted on the genetic susceptibility of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), two of which consistently identified tagging single nucleotide polymorphisms (SNPs) around HLA-DQ/DR. In contrast, large multi-centre association studies between HBV genotype, mutations and the risk of HCC are relatively rare, and their interactions with host variants are even less. We performed a multi-centre study of 1,507 HBV-related HCC cases and 1,560 HBV persistent carriers as controls to evaluate the effects of HBV genotype, mutations, GWAS-identified HLA-DQ/DR SNPs (rs9272105 and rs9275319) and their interactions on HCC risk. We found HBV genotype C was more frequent in HBV-related HCC. And 11 HBV hotspot mutations were independently and significantly associated with HCC risk. We also detected significant interactions of rs9272105 with both the HBV genotype and mutations. Through stepwise regression analysis, HBV genotype, the 11 mutations, HLA-DQ/DR SNPs, and the interaction of rs9272105 with mutation A1752G were all entered into the HCC prediction model, and the area under the curve for the panel including the HLA-DQ/DR SNPs, HBV genotype and mutations was 0.840. The HBV genotype, the mutations and the HLA-DQ/DR SNPs may serve as biomarkers for the surveillance of HBV persistent carriers.
authors.affiliation: Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center For Cancer Personalized Medicine, Cancer Center, School of Public Health, Nanjing Medical University, Nanjing, China.|Nanjing Maternity and Child Health Care Institute, Nanjing Maternity and Child Health Care Hospital Affiliated with Nanjing Medical University, Nanjing, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Wen
authors.affiliation: Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center For Cancer Personalized Medicine, Cancer Center, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Ci
authors.initials: C
authors.lastname: Song
authors.affiliation: State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, China.|Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China.|Fudan Center for genetic Epidemiology and Center for Genetic Translational Medicine and Prevention, Fudan University, Shanghai, China.
authors.forename: Deke
authors.initials: D
authors.lastname: Jiang
authors.affiliation: School of Life Sciences, Northwest University, Xi'an, China.|National Engineering Research Center for Miniaturized Detection Systems, Xi'an, China.
authors.forename: Tianbo
authors.initials: T
authors.lastname: Jin
authors.affiliation: Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center For Cancer Personalized Medicine, Cancer Center, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Juncheng
authors.initials: J
authors.lastname: Dai
authors.affiliation: Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center For Cancer Personalized Medicine, Cancer Center, School of Public Health, Nanjing Medical University, Nanjing, China.|Jiangsu Province Center for Disease Prevention and Control, Nanjing, China.
authors.forename: Liguo
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Jiaze
authors.initials: J
authors.lastname: An
authors.affiliation: Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center For Cancer Personalized Medicine, Cancer Center, School of Public Health, Nanjing Medical University, Nanjing, China.|Pathology Center and Department of Pathology, Soochow University, Suzhou, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology, Huai'an First People's Hospital of Nanjing Medical University, Huai'an, China.
authors.forename: Shijie
authors.initials: S
authors.lastname: Ma
authors.affiliation: Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center For Cancer Personalized Medicine, Cancer Center, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Na
authors.initials: N
authors.lastname: Qin
authors.affiliation: Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center For Cancer Personalized Medicine, Cancer Center, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Liang
authors.affiliation: Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center For Cancer Personalized Medicine, Cancer Center, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Jiaping
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center For Cancer Personalized Medicine, Cancer Center, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Hepatobiliary Surgery, Nantong Tumor Hospital, Nantong, China.
authors.forename: Linlin
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Hepatobiliary Surgery, Nantong Tumor Hospital, Nantong, China.
authors.forename: Jibin
authors.initials: J
authors.lastname: Liu
authors.affiliation: Digestive Endoscopy Center, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.affiliation: National Engineering Research Center for Miniaturized Detection Systems, Xi'an, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Geng
authors.affiliation: School of Life Sciences, Northwest University, Xi'an, China.|National Engineering Research Center for Miniaturized Detection Systems, Xi'an, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Chen
authors.affiliation: Jiangsu Province Center for Disease Prevention and Control, Nanjing, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Epidemiology, Qidong Liver Cancer Institute, Qidong, China.|Tumor Institute, Nantong Tumor Hospital, Nantong, China.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Chen
authors.affiliation: Jiangsu Province Center for Disease Prevention and Control, Nanjing, China.
authors.forename: Fengcai
authors.initials: F
authors.lastname: Zhu
authors.affiliation: Jiangsu Province Center for Disease Prevention and Control, Nanjing, China.
authors.forename: Yefei
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, China.
authors.forename: Long
authors.initials: L
authors.lastname: Yu
authors.affiliation: Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center For Cancer Personalized Medicine, Cancer Center, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Hongbing
authors.initials: H
authors.lastname: Shen
authors.affiliation: Jiangsu Province Center for Disease Prevention and Control, Nanjing, China.
authors.forename: Xiangjun
authors.initials: X
authors.lastname: Zhai
authors.affiliation: State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, China.|Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China.|Fudan Center for genetic Epidemiology and Center for Genetic Translational Medicine and Prevention, Fudan University, Shanghai, China.|Center for Cancer Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center For Cancer Personalized Medicine, Cancer Center, School of Public Health, Nanjing Medical University, Nanjing, China.|Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing, China.
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Hu
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000821:virology; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics*; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000821:virology; D008297:Male; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D012372:ROC Curve
chemical_list: D006680:HLA Antigens