title: Epidermal growth factor receptor pathway polymorphisms and the prognosis of hepatocellular carcinoma.
abstract: The EGFR signaling pathway is important in the control of vital processes in the carcinogenesis of hepatocellular carcinoma (HCC), including cell survival, cell cycle progression, tumor invasion and angiogenesis. In the current study, we aim to assess if genetic variants in the genes of the EGFR signaling pathway are associated with the prognosis of HCC. We genotyped 36 single nucleotide polymorphisms (SNP) in four core genes (EGF, EGFR, VEGF, and VEGFR2) by using DNA from blood samples of 363 HCC patients with surgical resection. The associations between genotypes and overall survival (OS) and disease-free survival (DFS) were estimated using the Kaplan-Meier method. Hazard ratios (HRs) and 95% confident intervals (CIs) were estimated for the multivariate survival analyses by Cox proportional hazards regression models, adjusting for age, gender, family history, HBsAg and AFP. We found that five SNPs in the VEGFR2 gene were significantly associated with clinical outcomes of HCC patients. Among them, four SNPs (rs7692791, rs2305948, rs13109660, rs6838752) were associated with OS (p=0.035, 0.038, 0.029 and 0.028, respectively), and two SNPs (rs7692791 and rs2034965) were associated with DFS (p=0.039 and 0.017, respectively). Particularly, rs7692791 TT genotype was associated with both reduced OS (p=0.037) and DFS (p=0.043). However, only one SNP rs2034965 with the AA genotype was shown to be an independent effect on DFS (p=0.009) in the multivariate analysis. None of the other 31 polymorphisms or 9 haplotypes attained from the four genes was significantly associated with OS or DFS. Our results illustrated the potential use of VEGFR2 polymorphisms as prognostic markers for HCC patients.
authors: 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: Wenjia
authors: W
authors: Wang
authors: State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University Shanghai, China.
authors: Xiao-Pin
authors: XP
authors: Ma
authors: 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: Zhuqing
authors: Z
authors: Shi
authors: 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: Pengyin
authors: P
authors: Zhang
authors: State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University Shanghai, China.
authors: Dong-Lin
authors: DL
authors: Ding
authors: State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University Shanghai, China.
authors: Hui-Xing
authors: HX
authors: Huang
authors: State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University Shanghai, China.
authors: Hexi Ge
authors: HG
authors: Saiyin
authors: Qidong Liver Cancer Institute, Qidong People's Hospital Qidong, Jiangsu, China.
authors: Tao-Yang
authors: TY
authors: Chen
authors: Qidong Liver Cancer Institute, Qidong People's Hospital Qidong, Jiangsu, China.
authors: Pei-Xin
authors: PX
authors: Lu
authors: Qidong Liver Cancer Institute, Qidong People's Hospital Qidong, Jiangsu, China.
authors: Neng-Jin
authors: NJ
authors: Wang
authors: 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: Hongjie
authors: H
authors: Yu
authors: Center for Cancer Genomics, Wake Forest University School of Medicine Winston-Salem, North Carolina, USA.
authors: Jielin
authors: J
authors: Sun
authors: Center for Cancer Genomics, Wake Forest University School of Medicine Winston-Salem, North Carolina, USA.
authors: S Lilly
authors: SL
authors: Zheng
authors: 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: Long
authors: L
authors: Yu
authors: 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: Jianfeng
authors: J
authors: Xu
authors: 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.
authors: De-Ke
authors: DK
authors: Jiang
keywords: EGF; EGFR; Hepatocellular carcinoma; VEGF; VEGFR2; genetic polymorphisms; survival
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