title: Genetic variations in genes of metabolic enzymes predict postoperational prognosis of patients with colorectal cancer.
abstract: BACKGROUND
  Genetic alterations in tricarboxylic acid (TCA) cycle metabolic enzymes were recently linked to various cancers. However, the associations of single nucleotide polymorphisms (SNPs) in genes of these enzymes have not been well studied.
  
  
  METHODS
  We genotyped 16 SNPs from 7 genes encoding TCA cycle metabolic enzymes in 697 colorectal carcinoma (CRC) patients receiving surgical resection and analyzed their associations with clinical outcomes by multivariate Cox proportional hazard model. Then, the significant results were validated in another cohort of 256 CRC patients.
  
  
  RESULTS
  We identified 4 SNPs in 2 genes had significant associations with CRC death risk and 5 SNPs in 3 genes had significant associations with CRC recurrence risk. Similar significant results were confirmed for rs4131826 in SDHC gene, rs544184 in SDHD gene and rs12071124 in FH gene in a validation cohort. Further analysis indicated that unfavorable genotypes exhibited a significant cumulative effect on overall and recurrence-free survival in a dose-dependent manner. Moreover, survival tree analysis indicated that SNP rs4131826 in SDHC gene and SNP rs12071124 in FH gene were the primary factors contributing to the different overall survival time and recurrence-free survival time of CRC patients, respectively. Immunohistochemical analysis further validated the effect of rs4131826 and rs544184 on expression of SDHC and SDHD in tissue samples.
  
  
  CONCLUSIONS
  Our study suggests that SNPs in TCA cycle metabolic enzymes might be significantly associated with clinical outcomes in Chinese population diagnosed with CRC. Further functional and validated studies are warranted to expend our results to clinical utility.
authors.affiliation: Department of General Surgery, The General Hospital of PLA, Beijing, 100853, China.
authors.forename: Guanglong
authors.initials: G
authors.lastname: Dong
authors.affiliation: Department of General Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Xianli
authors.initials: X
authors.lastname: He
authors.affiliation: State Key Laboratory of Cancer Biology, Experimental Teaching Center of Basic Medicine, Fourth Military Medical University, 169 Changle West Road, Xi'an, Shaanxi, 710032, China.
authors.forename: Yibing
authors.initials: Y
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Cancer Biology, Experimental Teaching Center of Basic Medicine, Fourth Military Medical University, 169 Changle West Road, Xi'an, Shaanxi, 710032, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Cao
authors.affiliation: State Key Laboratory of Cancer Biology, Experimental Teaching Center of Basic Medicine, Fourth Military Medical University, 169 Changle West Road, Xi'an, Shaanxi, 710032, China.
authors.forename: Jiaojiao
authors.initials: J
authors.lastname: Wang
authors.affiliation: Xijing Hospital of Digestive Disease, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Xiaonan
authors.initials: X
authors.lastname: Liu
authors.affiliation: Central Laboratory, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, China.
authors.forename: Shukui
authors.initials: S
authors.lastname: Wang
authors.affiliation: Institute of Pharmacy, Pharmaceutical College of Henan University, 85 Minglun Street, Kaifeng, Henan, 475001, China. shaoguiwan@126.com.
authors.forename: Shaogui
authors.initials: S
authors.lastname: Wan
authors.affiliation: State Key Laboratory of Cancer Biology, Experimental Teaching Center of Basic Medicine, Fourth Military Medical University, 169 Changle West Road, Xi'an, Shaanxi, 710032, China. xingjinliang@163.com.
authors.forename: Jinliang
authors.initials: J
authors.lastname: Xing
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D005649:Fumarate Hydratase / Q000235:genetics*; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D013385:Succinate Dehydrogenase / Q000235:genetics*; D016019:Survival Analysis
chemical_list: D008565:Membrane Proteins; C108096:SDHC protein, human; C491545:SDHD protein, human; D013385:Succinate Dehydrogenase; D005649:Fumarate Hydratase