title: Genetic variants in genes of tricarboxylic acid cycle key enzymes predict postsurgical overall survival of patients with hepatocellular carcinoma.
abstract: BACKGROUND
  Metabolic reprogramming is a hallmark of cancer, including the alterations of activity and expression in tricarboxylic acid (TCA) cycle key enzymes. However, the significance of single nucleotide polymorphisms (SNPs) in genes encoding these key enzymes has not been investigated in hepatocellular carcinoma (HCC).
  
  
  METHODS
  In this study, 17 SNPs in seven genes encoding three TCA cycle enzyme families (SDH, FH, and IDH) were genotyped in 492 HCC patients with surgical treatment and their association with overall survival (OS) was analyzed.
  
  
  RESULTS
  Five SNPs in four genes were identified to be associated with OS in HCC patients. Among them, rs3935401 in the 3' untranslated region of SDHC exhibited the most significant association (P < 0.001). The unfavorable genotype of these five SNPs showed a significant accumulative effect on the prognosis of HCC patients, with a P for trend of <0.001. Furthermore, the haplotype group consisting of wild type in rs4131826 and variant in rs3935401 was significantly associated with increased risk of death in HCC patients. Survival tree analysis indicated that variant genotype of rs3935401 was the primary risk factor contributing to the prediction of OS in HCC patients.
  
  
  CONCLUSIONS
  SNPs in TCA cycle key enzyme genes may serve as potential biomarkers to predict the OS in HCC patients.
authors: State Key Laboratory of Cancer Biology and Experimental Teaching Center of Basic Medicine, Fourth Military Medical University, Xi'an, China.
authors: Xiaohong
authors: X
authors: Du
authors: Shaogui
authors: S
authors: Wan
authors: Yibing
authors: Y
authors: Chen
authors: Ping
authors: P
authors: Qu
authors: Xiaojun
authors: X
authors: Huang
authors: Xiaohe
authors: X
authors: Yu
authors: Hushan
authors: H
authors: Yang
authors: Yiguan
authors: Y
authors: Zhang
authors: Jinliang
authors: J
authors: Xing
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000401:mortality* / Q000601:surgery; D002952:Citric Acid Cycle / Q000235:genetics; D005500:Follow-Up Studies; D005649:Fumarate Hydratase / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D008113:Liver Neoplasms / Q000235:genetics / Q000401:mortality* / Q000601:surgery; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D013385:Succinate Dehydrogenase / Q000235:genetics*; D015996:Survival Rate
chemical_list: D007521:Isocitrate Dehydrogenase; D013385:Succinate Dehydrogenase; D005649:Fumarate Hydratase