title: SNP rs2057482 in HIF1A gene predicts clinical outcome of aggressive hepatocellular carcinoma patients after surgery.
abstract: Hypoxia-inducible factor 1α (HIF-1α) plays an important role in tumor growth and metastasis. Genetic variations of HIF1A gene have been shown to influence the developing risk and prognosis in many types of human malignancies. However, their association with clinical outcomes of hepatocellular carcinoma (HCC) patients remains unclear. To investigate the predictive role of single nucleotide polymorphisms (SNPs) in HIF1A gene in HCC patients' outcomes, we genotyped three functional SNPs (rs2057482, rs1957757 and rs2301113) in HIF1A gene and assessed their associations with clinicopathological parameters and prognosis of 492 surgical HCC patients. The patients with variant alleles (CT+TT) of SNP rs2057482 had a significantly lower recurrence risk when compared with patients with the CC genotype. In stratified analysis, the protective effect of rs2057482 CT+TT genotype was more evident in patients with adverse strata, compared with patients with favorable strata. Additionally, strong joint predictive effect between rs2057482 genotypes and AFP level, stage or differentiation were observed. Functional assay also indicated the significant effect of rs2057482 on gene expression. In conclusion, SNP rs2057482 in HIF1A gene is significantly associated with clinical outcomes of Chinese HCC patients after surgery, especially in those with aggressive status, which warrants further validation in other patient populations.
authors.affiliation: State Key Laboratory of Cancer Biology, Cell Engineering Research Center &Department of Cell Biology, Fourth Military Medical University, Xi'an, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Cancer Biology, Cell Engineering Research Center &Department of Cell Biology, Fourth Military Medical University, Xi'an, China.
authors.forename: Deyang
authors.initials: D
authors.lastname: Li
authors.affiliation: Experimental Teaching Center of Basic Medicine, Fourth Military Medical University, Xi'an, China.
authors.forename: Yibing
authors.initials: Y
authors.lastname: Chen
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 Pain treatment, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China.
authors.forename: Kan
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of liver Surgery, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: Zhuding
authors.initials: Z
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Cancer Biology, Cell Engineering Research Center &Department of Cell Biology, Fourth Military Medical University, Xi'an, China.
authors.forename: Zhinan
authors.initials: Z
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Cancer Biology, Cell Engineering Research Center &Department of Cell Biology, Fourth Military Medical University, Xi'an, China.|Experimental Teaching Center of Basic Medicine, Fourth Military Medical University, Xi'an, China.
authors.forename: Jinliang
authors.initials: J
authors.lastname: Xing
mesh_terms: D044466:Asian People / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000208:ethnology / Q000235:genetics* / Q000601:surgery; D045744:Cell Line, Tumor; D002681:China; D005260:Female; D005500:Follow-Up Studies; D005787:Gene Frequency; D005838:Genotype; D057809:HEK293 Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics*; D008113:Liver Neoplasms / Q000208:ethnology / Q000235:genetics* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D017063:Outcome Assessment, Health Care / Q000379:methods / Q000706:statistics & numerical data; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D016016:Proportional Hazards Models; D012307:Risk Factors; D016019:Survival Analysis
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit