title: Genetic polymorphisms in apoptosis-related genes and the prognosis of hepatocellular carcinoma.
abstract: The apoptotic pathway is important in the control of vital processes of hepatocellular carcinoma (HCC). In the current study, we aimed to determine whether apoptotic gene-related polymorphisms modified HCC prognosis. We genotyped 16 single nucleotide polymorphisms (SNPs) in 10 core genes (TP53, TP53INP1, TP53BP1, CDKN2A, CDKN1A, CDKN1B, MDM2, BAX, CCDN1 and BCL2) in the apoptotic pathway by using DNA from blood samples of 362 HCC patients receiving surgical resection of HCC tumor. The associations between genotypes/haplotypes of the 10 genes and overall survival (OS) of HCC patients were assessed using the Cox proportional hazards model. We found one CDKN1B haplotype CCT/ACT (constructed by rs36228499 C>A, rs34330 C>T and rs2066827 T>G) significantly associated with decreased OS of HCC patients, compared to the common haplotype ACT/CTT both in univariate analysis (P=0.013, HR=1.198, 95% CI: 1.039-1.381) and multivariate analysis (P=0.006, HR=1.224, 95% CI: 1.059-1.413). We also find two SNPs (rs560191 G>C and rs2602141 T>G) in TP53BP1 shown to be marginally significantly associated with decreased OS of HCC patients. However, none of the other SNPs or haplotypes were significantly associated with HCC OS. Our results illustrated the potential use of CDKN1B haplotype as a prognostic marker for HCC patients with surgical resection of tumor.
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 ; Center for genetic Epidemiology, School of Life Sciences, Fudan University Shanghai, China ; Center for Genetic Translational Medicine and Prevention, School of Public Health, Fudan University Shanghai, China ; Fudan Institute of Urology, Huashan Hospital, Fudan University Shanghai, China ; Department of Urology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University Shanghai, China ; Center for Cancer Genomics, Wake Forest University School of Medicine Winston-Salem, North Carolina, USA.
authors.forename: Guo-Peng
authors.initials: GP
authors.lastname: Yu
authors.affiliation: Center for Genetic Translational Medicine and Prevention, School of Public Health, Fudan University Shanghai, China.
authors.forename: Qian-Yi
authors.initials: QY
authors.lastname: Xiao
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 ; Center for genetic Epidemiology, School of Life Sciences, Fudan University Shanghai, China ; Center for Genetic Translational Medicine and Prevention, School of Public Health, Fudan University Shanghai, China.
authors.forename: Zhu-Qing
authors.initials: ZQ
authors.lastname: Shi
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: Li-Sha
authors.initials: LS
authors.lastname: Tang
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: Xiao-Pin
authors.initials: XP
authors.lastname: Ma
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: Lu-Yao
authors.initials: LY
authors.lastname: Zhang
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 ; Center for genetic Epidemiology, School of Life Sciences, Fudan University Shanghai, China ; Center for Genetic Translational Medicine and Prevention, School of Public Health, Fudan University Shanghai, China.
authors.forename: Hai-Tao
authors.initials: HT
authors.lastname: Chen
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 ; Center for genetic Epidemiology, School of Life Sciences, Fudan University Shanghai, China ; Center for Genetic Translational Medicine and Prevention, School of Public Health, Fudan University Shanghai, China.
authors.forename: Wen-Jia
authors.initials: WJ
authors.lastname: Wang
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 ; Center for genetic Epidemiology, School of Life Sciences, Fudan University Shanghai, China ; Center for Genetic Translational Medicine and Prevention, School of Public Health, Fudan University Shanghai, China.
authors.forename: Peng-Yin
authors.initials: PY
authors.lastname: Zhang
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: Dong-Lin
authors.initials: DL
authors.lastname: Ding
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: Hui-Xing
authors.initials: HX
authors.lastname: Huang
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: Hexige
authors.initials: H
authors.lastname: Saiyin
authors.affiliation: Qidong Liver Cancer Institute, Qidong People's Hospital Qidong, Jiangsu, China.
authors.forename: Tao-Yang
authors.initials: TY
authors.lastname: Chen
authors.affiliation: Qidong Liver Cancer Institute, Qidong People's Hospital Qidong, Jiangsu, China.
authors.forename: Pei-Xin
authors.initials: PX
authors.lastname: Lu
authors.affiliation: Qidong Liver Cancer Institute, Qidong People's Hospital Qidong, Jiangsu, China.
authors.forename: Neng-Jin
authors.initials: NJ
authors.lastname: Wang
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 ; Center for genetic Epidemiology, School of Life Sciences, Fudan University Shanghai, China ; Center for Genetic Translational Medicine and Prevention, School of Public Health, Fudan University Shanghai, China.
authors.forename: Hong-Jie
authors.initials: HJ
authors.lastname: Yu
authors.affiliation: Center for Cancer Genomics, Wake Forest University School of Medicine Winston-Salem, North Carolina, USA.
authors.forename: Jie-Lin
authors.initials: JL
authors.lastname: Sun
authors.affiliation: Center for Cancer Genomics, Wake Forest University School of Medicine Winston-Salem, North Carolina, USA ; Center for Genomic Cancer Research, North Shore University Health System Evanston, IL, USA.
authors.forename: S Lilly
authors.initials: SL
authors.lastname: Zheng
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 ; Center for genetic Epidemiology, School of Life Sciences, Fudan University Shanghai, China ; Center for Genetic Translational Medicine and Prevention, School of Public Health, Fudan University Shanghai, China ; Fudan Institute of Urology, Huashan Hospital, Fudan University Shanghai, China ; Center for Genomic Cancer Research, North Shore University Health System Evanston, IL, USA.
authors.forename: Jian-Feng
authors.initials: JF
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University Shanghai, China ; Institute of Biomedical Science, Fudan University Shanghai, China.
authors.forename: Long
authors.initials: L
authors.lastname: Yu
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 ; Center for genetic Epidemiology, School of Life Sciences, Fudan University Shanghai, China ; Center for Genetic Translational Medicine and Prevention, School of Public Health, Fudan University Shanghai, China ; Center for Cancer Genomics, Wake Forest University School of Medicine Winston-Salem, North Carolina, USA ; Center for Genomic Cancer Research, North Shore University Health System Evanston, IL, USA.
authors.forename: De-Ke
authors.initials: DK
authors.lastname: Jiang
keywords: CDKN1B; Hepatocellular carcinoma; apoptosis; genetic polymorphisms; survival