title: Genetic polymorphism in a VEGF-independent angiogenesis gene ANGPT1 and overall survival of colorectal cancer patients after surgical resection.
abstract: BACKGROUND
  The VEGF-independent angiogenic signaling plays an important role in the development of colorectal cancer (CRC). However, its implication in the clinical outcome of CRC has not been reported. This study aimed to investigate the association between genetic variations in several major VEGF-independent signaling pathway genes and the overall survival of CRC patients.
  
  
  METHODS
  Seven single nucleotide polymorphisms (SNPs) in four important VEGF-independent angiogenic genes (ANGPT1, AMOT, DLL4 and ENG) were genotyped in a Chinese population with 408 CRC patients.
  
  
  RESULTS
  One SNP, rs1954727 in ANGPT1, was significantly associated with CRC overall survival. Compared to patients with the homozygous wild-type genotype of rs1954727, those with heterozygous and homozygous variant genotypes exhibited a favorable overall survival with a hazard ratio (HR) of 0.89 (95% confidence interval [CI] 0.55-1.43, P = 0.623), and 0.32 (95% CI 0.15-0.71, P = 0.005), respectively (P trend = 0.008). In stratified analysis, this association remained significant in patients receiving chemotherapy (P trend = 0.012), but not in those without chemotherapy. We further evaluated the effects of chemotherapy on CRC survival that was stratified by rs1954727 genotypes. We found that chemotherapy resulted in a significantly better overall survival in the CRC patients (HR = 0.44, 95% CI 0.26-0.75, P = 0.002), which was especially prominent in those patients with the heterozygous genotype of rs1954727 (HR = 0.45, 95%CI 0.22-0.92, P = 0.028).
  
  
  CONCLUSIONS
  Our data suggest that rs1954727 in ANGPT1 gene might be a prognostic biomarker for the overall survival of CRC patients, especially in those receiving chemotherapy, a finding that warrants validation in larger independent populations.
authors.affiliation: Department of Hepatobiliary Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.
authors.forename: Jingyao
authors.initials: J
authors.lastname: Dai
authors.forename: Shaogui
authors.initials: S
authors.lastname: Wan
authors.forename: Feng
authors.initials: F
authors.lastname: Zhou
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Myers
authors.forename: Xu
authors.initials: X
authors.lastname: Guo
authors.forename: Bingshan
authors.initials: B
authors.lastname: Li
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Fu
authors.forename: Juan P
authors.initials: JP
authors.lastname: Palazzo
authors.forename: Kefeng
authors.initials: K
authors.lastname: Dou
authors.forename: Hushan
authors.initials: H
authors.lastname: Yang
authors.forename: Jinliang
authors.initials: J
authors.lastname: Xing
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D042683:Angiopoietin-1 / Q000235:genetics*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D044466:Asian People / Q000235:genetics / Q000706:statistics & numerical data; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D003131:Combined Modality Therapy / Q000706:statistics & numerical data; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D013534:Survival
chemical_list: C467630:ANGPT1 protein, human; D042683:Angiopoietin-1; D000970:Antineoplastic Agents