title: Functional polymorphisms of ATP citrate lyase gene predicts clinical outcome of patients with advanced colorectal cancer.
abstract: BACKGROUND
  Previous studies have demonstrated that ATP citrate lyase (ACLY) plays an important role in the development of many cancers. Our current study aims to assess the effects of functional single nucleotide polymorphisms (SNPs) in ACLY gene on recurrence and survival of colorectal cancer (CRC) patients.
  
  
  METHODS
  A total of 697 resected Chinese CRC patients were included in this study. Two functional single nucleotide polymorphisms in ACLY gene were examined using the Sequenom iPLEX genotyping system. Multivariate Cox proportional hazards model and Kaplan-Meier curve were used for the prognosis analysis.
  
  
  RESULTS
  Multivariate Cox regression analysis showed that there was no significant association between SNPs in ACLY gene and the prognosis of total patient cohort. However, in patients with stage III + IV diseases, the two functional SNPs (rs2304497 and rs9912300) exhibited a significant association with the risks of death (HR = 0.47, 95% CI = 0.24-0.90 and HR = 0.59, 95% CI = 0.37-0.92, respectively) and recurrence (HR = 0.46, 95% CI = 0.24-0.86 and HR = 0.54, CI = 0.35-0.83, respectively). Kaplan-Meier analysis indicated that those CRC patients carrying heterozygous (WV) or homozygous variant (VV) genotypes in rs2304497 and rs9912300 had significantly better overall survival (OS) and recurrence-free survival (RFS). Moreover, we observed remarkable cumulative effects of these two SNPs on overall survival and recurrence-free survival (P for trend = 0.012 and 0.003, respectively). Compared with patients carrying zero unfavorable genotype, those carrying two unfavorable genotypes had a 2.24-fold and 2.33-fold increase of death and recurrence risks, respectively.
  
  
  CONCLUSIONS
  The SNPs in ACLY gene may serve as independent prognostic markers for patients with advanced stage CRC.
authors.affiliation: Department of General Surgery, Tangdu Hospital, Fourth Military Medical University, 169 West Changle Street, Xi'an, 710032, China. 58142293@qq.com.|State Key Laboratory of Cancer Biology, Experimental Teaching Center of Basic Medicine, Fourth Military Medical University, Xi'an, 710032, China. 58142293@qq.com.
authors.forename: Shuang
authors.initials: S
authors.lastname: Xie
authors.affiliation: Department of General Surgery, Tangdu Hospital, Fourth Military Medical University, 169 West Changle Street, Xi'an, 710032, China. zhoufeng3899665@163.com.|Department of General Surgery, Huaihai Hospital, Xuzhou Medical College, Xuzhou, Jiangsu, 221004, China. zhoufeng3899665@163.com.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Cancer Biology, Experimental Teaching Center of Basic Medicine, Fourth Military Medical University, Xi'an, 710032, China. 980078421@qq.com.
authors.forename: Jiaojiao
authors.initials: J
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Cancer Biology, Experimental Teaching Center of Basic Medicine, Fourth Military Medical University, Xi'an, 710032, China. caohaiyan7@163.com.
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, Xi'an, 710032, China. chenyibing@foxmail.com.
authors.forename: Yibing
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Xijing Hospital of Digestive Disease, Fourth Military Medical University, Xi'an, 710032, China. liuxnys@fmmu.edu.cn.
authors.forename: Xiaonan
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of General Surgery, Huaihai Hospital, Xuzhou Medical College, Xuzhou, Jiangsu, 221004, China. zzhlyn@163.com.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China. daijingyao2006@163.com.
authors.forename: Jingyao
authors.initials: J
authors.lastname: Dai
authors.affiliation: Department of General Surgery, Tangdu Hospital, Fourth Military Medical University, 169 West Changle Street, Xi'an, 710032, China. wanghe@fmmu.edu.cn.
authors.forename: Xianli
authors.initials: X
authors.lastname: He
mesh_terms: D001275:ATP Citrate (pro-S)-Lyase / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000401:mortality; D003131:Combined Modality Therapy; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000201:enzymology / Q000235:genetics* / Q000401:mortality; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D015996:Survival Rate; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D001275:ATP Citrate (pro-S)-Lyase